@article{LauLiuMaieretal.2021, author = {Lau, Skadi and Liu, Yue and Maier, Anna and Braune, Steffen and Gossen, Manfred and Neffe, Axel T. and Lendlein, Andreas}, title = {Establishment of an in vitro thrombogenicity test system with cyclic olefin copolymer substrate for endothelial layer formation}, series = {MRS communications / a publication of the Materials Research Society}, volume = {11}, journal = {MRS communications / a publication of the Materials Research Society}, number = {5}, publisher = {Springer}, address = {Berlin}, issn = {2159-6867}, doi = {10.1557/s43579-021-00072-6}, pages = {559 -- 567}, year = {2021}, abstract = {In vitro thrombogenicity test systems require co-cultivation of endothelial cells and platelets under blood flow-like conditions. Here, a commercially available perfusion system is explored using plasma-treated cyclic olefin copolymer (COC) as a substrate for the endothelial cell layer. COC was characterized prior to endothelialization and co-cultivation with platelets under static or flow conditions. COC exhibits a low roughness and a moderate hydrophilicity. Flow promoted endothelial cell growth and prevented platelet adherence. These findings show the suitability of COC as substrate and the importance of blood flow-like conditions for the assessment of the thrombogenic risk of drugs or cardiovascular implant materials.}, language = {en} } @article{TungSunWangetal.2021, author = {Tung, Wing Tai and Sun, Xianlei and Wang, Weiwei and Xu, Xun and Ma, Nan and Lendlein, Andreas}, title = {Structure, mechanical properties and degradation behavior of electrospun PEEU fiber meshes and films}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {6}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, number = {10}, publisher = {Springer Nature Switzerland AG}, address = {Cham}, issn = {2059-8521}, doi = {10.1557/s43580-020-00001-0}, pages = {276 -- 282}, year = {2021}, abstract = {The capability of a degradable implant to provide mechanical support depends on its degradation behavior. Hydrolytic degradation was studied for a polyesteretherurethane (PEEU70), which consists of poly(p-dioxanone) (PPDO) and poly(epsilon-caprolactone) (PCL) segments with a weight ratio of 70:30 linked by diurethane junction units. PEEU70 samples prepared in the form of meshes with average fiber diameters of 1.5 mu m (mesh1.5) and 1.2 mu m (mesh1.2), and films were sterilized and incubated in PBS at 37 degrees C with 5 vol\% CO2 supply for 1 to 6 weeks. Degradation features, such as cracks or wrinkles, became apparent from week 4 for all samples. Mass loss was found to be 11 wt\%, 6 wt\%, and 4 wt\% for mesh1.2, mesh1.5, and films at week 6. The elongation at break decreased to under 20\% in two weeks for mesh1.2. In case of the other two samples, this level of degradation was achieved after 4 weeks. The weight average molecular weight of both PEEU70 mesh and film samples decreased to below 30 kg/mol when elongation at break dropped below 20\%. The time period of sustained mechanical stability of PEEU70-based meshes depends on the fiber diameter and molecular weight.}, language = {en} } @article{ZhouXuMaetal.2021, author = {Zhou, Shuo and Xu, Xun and Ma, Nan and Jung, Friedrich and Lendlein, Andreas}, title = {Influence of sterilization conditions on sulfate-functionalized polyGGE}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {79}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {4}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-211241}, pages = {597 -- 608}, year = {2021}, abstract = {Sulfated biomolecules are known to influence numerous biological processes in all living organisms. Particularly, they contribute to prevent and inhibit the hypercoagulation condition. The failure of polymeric implants and blood contacting devices is often related to hypercoagulation and microbial contamination. Here, bioactive sulfated biomacromolecules are mimicked by sulfation of poly(glycerol glycidyl ether) (polyGGE) films. Autoclaving, gamma-ray irradiation and ethylene oxide (EtO) gas sterilization techniques were applied to functionalized materials. The sulfate group density and hydrophilicity of sulfated polymers were decreased while chain mobility and thermal degradation were enhanced post autoclaving when compared to those after EtO sterilization. These results suggest that a quality control after sterilization is mandatory to ensure the amount and functionality of functionalized groups are retained.}, language = {en} } @article{TungMaringXuetal.2022, author = {Tung, Wing Tai and Maring, Janita A. and Xu, Xun and Liu, Yue and Becker, Matthias and Somesh, Dipthi Bachamanda and Klose, Kristin and Wang, Weiwei and Sun, Xianlei and Ullah, Imran and Kratz, Karl and Neffe, Axel T. and Stamm, Christof and Ma, Nan and Lendlein, Andreas}, title = {In vivo performance of a cell and factor free multifunctional fiber mesh modulating postinfarct myocardial remodeling}, series = {Advanced Functional Materials}, volume = {32}, journal = {Advanced Functional Materials}, number = {31}, publisher = {Wiley}, address = {Weinheim}, issn = {1616-301X}, doi = {10.1002/adfm.202110179}, pages = {17}, year = {2022}, abstract = {Guidance of postinfarct myocardial remodeling processes by an epicardial patch system may alleviate the consequences of ischemic heart disease. As macrophages are highly relevant in balancing immune response and regenerative processes their suitable instruction would ensure therapeutic success. A polymeric mesh capable of attracting and instructing monocytes by purely physical cues and accelerating implant degradation at the cell/implant interface is designed. In a murine model for myocardial infarction the meshes are compared to those either coated with extracellular matrix or loaded with induced cardiomyocyte progenitor cells. All implants promote macrophage infiltration and polarization in the epicardium, which is verified by in vitro experiments. 6 weeks post-MI, especially the implantation of the mesh attenuates left ventricular adverse remodeling processes as shown by reduced infarct size (14.7\% vs 28-32\%) and increased wall thickness (854 mu m vs 400-600 mu m), enhanced angiogenesis/arteriogenesis (more than 50\% increase compared to controls and other groups), and improved heart function (ejection fraction = 36.8\% compared to 12.7-31.3\%). Upscaling as well as process controls is comprehensively considered in the presented mesh fabrication scheme to warrant further progression from bench to bedside.}, language = {en} } @article{XuNieWangetal.2021, author = {Xu, Xun and Nie, Yan and Wang, Weiwei and Ma, Nan and Lendlein, Andreas}, title = {Periodic thermomechanical modulation of toll-like receptor expression and distribution in mesenchymal stromal cells}, series = {MRS communications / a publication of the Materials Research Society}, volume = {11}, journal = {MRS communications / a publication of the Materials Research Society}, number = {4}, publisher = {Springer}, address = {Berlin}, issn = {2159-6867}, doi = {10.1557/s43579-021-00049-5}, pages = {425 -- 431}, year = {2021}, abstract = {Toll-like receptor (TLR) can trigger an immune response against virus including SARS-CoV-2. TLR expression/distribution is varying in mesenchymal stromal cells (MSCs) depending on their culture environments. Here, to explore the effect of periodic thermomechanical cues on TLRs, thermally controlled shape-memory polymer sheets with programmable actuation capacity were created. The proportion of MSCs expressing SARS-CoV-2-associated TLRs was increased upon stimulation. The TLR4/7 colocalization was promoted and retained in the endoplasmic reticula. The TLR redistribution was driven by myosin-mediated F-actin assembly. These results highlight the potential of boosting the immunity for combating COVID-19 via thermomechanical preconditioning of MSCs.}, language = {en} } @article{DengWangXuetal.2021, author = {Deng, Zijun and Wang, Weiwei and Xu, Xun and Ma, Nan and Lendlein, Andreas}, title = {Polydopamine-based biofunctional substrate coating promotes mesenchymal stem cell migration}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {6}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, number = {31}, publisher = {Springer Nature Switzerland AG}, address = {Cham}, issn = {2059-8521}, doi = {10.1557/s43580-021-00091-4}, pages = {739 -- 744}, year = {2021}, abstract = {Rapid migration of mesenchymal stem cells (MSCs) on device surfaces could support in vivo tissue integration and might facilitate in vitro organoid formation. Here, polydopamine (PDA) is explored as a biofunctional coating to effectively promote MSC motility. It is hypothesized that PDA stimulates fibronectin deposition and in this way enhances integrin-mediated migration capability. The random and directional cell migration was investigated by time-lapse microscopy and gap closure assay respectively, and analysed with softwares as computational tools. A higher amount of deposited fibronectin was observed on PDA substrate, compared to the non-coated substrate. The integrin beta 1 activation and focal adhesion kinase (FAK) phosphorylation at Y397 were enhanced on PDA substrate, but the F-actin cytoskeleton was not altered, suggesting MSC migration on PDA was regulated by integrin initiated FAK signalling. This study strengthens the biofunctionality of PDA coating for regulating stem cells and offering a way of facilitating tissue integration of devices.}, language = {en} } @article{MachatschekSaretiaLendlein2021, author = {Machatschek, Rainhard Gabriel and Saretia, Shivam and Lendlein, Andreas}, title = {Assessing the influence of temperature-memory creation on the degradation of copolyesterurethanes in ultrathin films}, series = {Advanced materials interfaces}, volume = {8}, journal = {Advanced materials interfaces}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {2196-7350}, doi = {10.1002/admi.202001926}, pages = {8}, year = {2021}, abstract = {Copolyesterurethanes (PDLCLs) based on oligo(epsilon-caprolactone) (OCL) and oligo(omega-pentadecalactone) (OPDL) segments are biodegradable thermoplastic temperature-memory polymers. The temperature-memory capability in these polymers with crystallizable control units is implemented by a thermomechanical programming process causing alterations in the crystallite arrangement and chain organization. These morphological changes can potentially affect degradation. Initial observations on the macroscopic level inspire the hypothesis that switching of the controlling units causes an accelerated degradation of the material, resulting in programmable degradation by sequential coupling of functions. Hence, detailed degradation studies on Langmuir films of a PDLCL with 40 wt\% OPDL content are carried out under enzymatic catalysis. The temperature-memory creation procedure is mimicked by compression at different temperatures. The evolution of the chain organization and mechanical properties during the degradation process is investigated by means of polarization-modulated infrared reflection absorption spectroscopy, interfacial rheology and to some extend by X-ray reflectivity. The experiments on PDLCL Langmuir films imply that degradability is not enhanced by thermal switching, as the former depends on the temperature during cold programming. Nevertheless, the thin film experiments show that the leaching of OCL segments does not induce further crystallization of the OPDL segments, which is beneficial for a controlled and predictable degradation.}, language = {en} } @article{NeffeLoewenbergJulichGruneretal.2021, author = {Neffe, Axel T. and L{\"o}wenberg, Candy and Julich-Gruner, Konstanze K. and Behl, Marc and Lendlein, Andreas}, title = {Thermally-induced shape-memory behavior of degradable gelatin-based networks}, series = {International journal of molecular sciences}, volume = {22}, journal = {International journal of molecular sciences}, number = {11}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms22115892}, pages = {15}, year = {2021}, abstract = {Shape-memory hydrogels (SMH) are multifunctional, actively-moving polymers of interest in biomedicine. In loosely crosslinked polymer networks, gelatin chains may form triple helices, which can act as temporary net points in SMH, depending on the presence of salts. Here, we show programming and initiation of the shape-memory effect of such networks based on a thermomechanical process compatible with the physiological environment. The SMH were synthesized by reaction of glycidylmethacrylated gelatin with oligo(ethylene glycol) (OEG) alpha,omega-dithiols of varying crosslinker length and amount. Triple helicalization of gelatin chains is shown directly by wide-angle X-ray scattering and indirectly via the mechanical behavior at different temperatures. The ability to form triple helices increased with the molar mass of the crosslinker. Hydrogels had storage moduli of 0.27-23 kPa and Young's moduli of 215-360 kPa at 4 degrees C. The hydrogels were hydrolytically degradable, with full degradation to water-soluble products within one week at 37 degrees C and pH = 7.4. A thermally-induced shape-memory effect is demonstrated in bending as well as in compression tests, in which shape recovery with excellent shape-recovery rates R-r close to 100\% were observed. In the future, the material presented here could be applied, e.g., as self-anchoring devices mechanically resembling the extracellular matrix.}, language = {en} } @article{BochoveGrijpmaLendleinetal.2021, author = {Bochove, Bas van and Grijpma, Dirk W. and Lendlein, Andreas and Sepp{\"a}l{\"a}, Jukka}, title = {Designing advanced functional polymers for medicine}, series = {European polymer journal : EPJ}, volume = {155}, journal = {European polymer journal : EPJ}, publisher = {Elsevier}, address = {Oxford}, issn = {0014-3057}, doi = {10.1016/j.eurpolymj.2021.110573}, pages = {2}, year = {2021}, language = {en} } @article{DengWangXuaetal.2020, author = {Deng, Zijun and Wang, Weiwei and Xua, Xun and Gould, Oliver E. C. and Kratz, Karl and Ma, Nan and Lendlein, Andreas}, title = {Polymeric sheet actuators with programmable bioinstructivity}, series = {PNAS}, volume = {117}, journal = {PNAS}, number = {4}, publisher = {National Academy of Sciences}, address = {Washington, DC}, issn = {1091-6490}, doi = {10.1073/pnas.1910668117}, pages = {1895 -- 1901}, year = {2020}, abstract = {Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSC5). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSC5 are interconnected via intracellular Ca2+. Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.}, language = {en} } @article{SaretiaMachatschekLendlein2021, author = {Saretia, Shivam and Machatschek, Rainhard Gabriel and Lendlein, Andreas}, title = {Degradation kinetics of oligo(ε-caprolactone) ultrathin films}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {6}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, number = {33}, publisher = {Springer Nature Switzerland AG}, address = {Cham}, issn = {2059-8521}, doi = {10.1557/s43580-021-00067-4}, pages = {790 -- 795}, year = {2021}, abstract = {The potential of using crystallinity as morphological parameter to control polyester degradation in acidic environments is explored in ultrathin films by Langmuir technique. Films of hydroxy or methacrylate end-capped oligo(epsilon-caprolactone) (OCL) are prepared at the air-water interface as a function of mean molecular area (MMA). The obtained amorphous, partially crystalline or highly crystalline ultrathin films of OCL are hydrolytically degraded at pH similar to 1.2 on water surface or on silicon surface as-transferred films. A high crystallinity reduces the hydrolytic degradation rate of the films on both water and solid surfaces. Different acceleration rates of hydrolytic degradation of semi-crystalline films are achieved either by crystals complete melting, partially melting, or by heating them below their melting temperatures. Semi-crystalline OCL films transferred via water onto a solid surface retain their crystalline morphology, degrade in a controlled manner, and are of interest as thermoswitchable coatings for cell substrates and medical devices.}, language = {en} } @article{TarazonaLizcanoMachatschekBalcuchoetal.2022, author = {Tarazona Lizcano, Natalia Andrea and Machatschek, Rainhard Gabriel and Balcucho, Jennifer and Castro-Mayorga, Jinneth Lorena and Saldarriaga, Juan Francisco and Lendlein, Andreas}, title = {Opportunities and challenges for integrating the development of sustainable polymer materials within an international circular (bio)economy concept}, series = {MRS energy \& sustainability : science \& technology \& socio-economics \& policy}, volume = {9}, journal = {MRS energy \& sustainability : science \& technology \& socio-economics \& policy}, number = {1}, publisher = {Springer Nature}, address = {London}, issn = {2329-2229}, doi = {10.1557/s43581-021-00015-7}, pages = {28 -- 34}, year = {2022}, abstract = {The production and consumption of commodity polymers have been an indispensable part of the development of our modern society. Owing to their adjustable properties and variety of functions, polymer-based materials will continue playing important roles in achieving the Sustainable Development Goals (SDG)s, defined by the United Nations, in key areas such as healthcare, transport, food preservation, construction, electronics, and water management. Considering the serious environmental crisis, generated by increasing consumption of plastics, leading-edge polymers need to incorporate two types of functions: Those that directly arise from the demands of the application (e.g. selective gas and liquid permeation, actuation or charge transport) and those that enable minimization of environmental harm, e.g., through prolongation of the functional lifetime, minimization of material usage, or through predictable disintegration into non-toxic fragments. Here, we give examples of how the incorporation of a thoughtful combination of properties/functions can enhance the sustainability of plastics ranging from material design to waste management. We focus on tools to measure and reduce the negative impacts of plastics on the environment throughout their life cycle, the use of renewable sources for their synthesis, the design of biodegradable and/or recyclable materials, and the use of biotechnological strategies for enzymatic recycling of plastics that fits into a circular bioeconomy. Finally, we discuss future applications for sustainable plastics with the aim to achieve the SDGs through international cooperation.
Leading-edge polymer-based materials for consumer and advanced applications are necessary to achieve sustainable development at a global scale. It is essential to understand how sustainability can be incorporated in these materials via green chemistry, the integration of bio-based building blocks from biorefineries, circular bioeconomy strategies, and combined smart and functional capabilities.}, language = {en} } @article{FolikumahBehlLendlein2021, author = {Folikumah, Makafui Y. and Behl, Marc and Lendlein, Andreas}, title = {Reaction behaviour of peptide-based single thiol-thioesters exchange reaction substrate in the presence of externally added thiols}, series = {MRS communications / a publication of the Materials Research Society}, volume = {11}, journal = {MRS communications / a publication of the Materials Research Society}, number = {4}, publisher = {Springer}, address = {Berlin}, issn = {2159-6859}, doi = {10.1557/s43579-021-00041-z}, pages = {402 -- 410}, year = {2021}, abstract = {Identification of patterns in chemical reaction pathways aids in the effective design of molecules for specific applications. Here, we report on model reactions with a water-soluble single thiol-thioester exchange (TTE) reaction substrate, which was designed taking in view biological and medical applications. This substrate consists of the thio-depsipeptide, Ac-Pro-Leu-Gly-SLeu-Leu-Gly-NEtSH (TDP) and does not yield foul-smelling thiol exchange products when compared with aromatic thiol containing single TTE substrates. TDP generates an alpha,omega-dithiol crosslinker in situ in a 'pseudo intramolecular' TTE. Competitive intermolecular TTE of TDP with externally added "basic" thiols increased the crosslinker concentration whilst "acidic" thiols decreased its concentration. TDP could potentially enable in situ bioconjugation and crosslinking applications.}, language = {en} } @article{HoffmannMachatschekLendlein2022, author = {Hoffmann, Falk and Machatschek, Rainhard Gabriel and Lendlein, Andreas}, title = {Analytical model and Monte Carlo simulations of polymer degradation with improved chain cut statistics}, series = {Journal of materials research : JMR}, volume = {37}, journal = {Journal of materials research : JMR}, number = {5}, publisher = {Springer}, address = {Heidelberg}, issn = {0884-2914}, doi = {10.1557/s43578-022-00495-4}, pages = {1093 -- 1101}, year = {2022}, abstract = {The degradation of polymers is described by mathematical models based on bond cleavage statistics including the decreasing probability of chain cuts with decreasing average chain length. We derive equations for the degradation of chains under a random chain cut and a chain end cut mechanism, which are compared to existing models. The results are used to predict the influence of internal molecular parameters. It is shown that both chain cut mechanisms lead to a similar shape of the mass or molecular mass loss curve. A characteristic time is derived, which can be used to extract the maximum length of soluble fragments l of the polymer. We show that the complete description is needed to extract the degradation rate constant k from the molecular mass loss curve and that l can be used to design polymers that lose less mechanical stability before entering the mass loss phase.}, language = {en} } @article{NeffeLoewenbergLendlein2021, author = {Neffe, Axel T. and L{\"o}wenberg, Candy and Lendlein, Andreas}, title = {Hydrogel networks by aliphatic dithiol Michael addition to glycidylmethacrylated gelatin}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {6}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, number = {33}, publisher = {Springer Nature Switzerland AG}, address = {Cham}, issn = {2059-8521}, doi = {10.1557/s43580-021-00136-8}, pages = {796 -- 800}, year = {2021}, abstract = {Functionalization of gelatin with glycidylmethacrylate (GMA-gelatin) enables network formation employing the double bond, so that the reaction is orthogonal to the inherent functional groups in the biomacromolecule. Here, network formation by crosslinking of GMA-gelatin with hexane 1,6-dithiol or nonane 1,9-dithiol to tailor properties and enable a shape-memory effect is shown by H-1 NMR and FT-IR spectroscopy. Hydrogel swelling (460-1900 vol\%) and mechanical properties (Young's modulus E = 59-512 kPa, elongation at break epsilon(b) = 44-127\%) depended on the molecular composition of the networks and temperature. Increased crosslinker length, thiol:methacrylate molar ratio, and precursor concentrations led to denser networks. Change of properties with temperature suggested adoption of triple helices by gelatin chains, forming physical netpoints at lower temperatures (< 20 degrees C). However, the limited freedom of the gelatin chains to move allowed only a minimal extent of triple helices formation, as it became apparent from the related signal in wide-angle X-ray scattering and the thermal transition associated to triple helices in some networks by DSC. The presented strategy is likely transferable to other biomacromolecules, and the results suggest that too short crosslinkers may result in a significant amount of grafting rather than network formation.}, language = {en} } @article{LauMaierBrauneetal.2021, author = {Lau, Skadi and Maier, Anna and Braune, Steffen and Gossen, Manfred and Lendlein, Andreas}, title = {Effect of endothelial culture medium composition on platelet responses to polymeric biomaterials}, series = {International journal of molecular sciences}, volume = {22}, journal = {International journal of molecular sciences}, number = {13}, publisher = {Molecular Diversity Preservation International}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms22137006}, pages = {13}, year = {2021}, abstract = {Near-physiological in vitro thrombogenicity test systems for the evaluation of blood-contacting endothelialized biomaterials requires co-cultivation with platelets (PLT). However, the addition of PLT has led to unphysiological endothelial cell (EC) detachment in such in vitro systems. A possible cause for this phenomenon may be PLT activation triggered by the applied endothelial cell medium, which typically consists of basal medium (BM) and nine different supplements. To verify this hypothesis, the influence of BM and its supplements was systematically analyzed regarding PLT responses. For this, human platelet rich plasma (PRP) was mixed with BM, BM containing one of nine supplements, or with BM containing all supplements together. PLT adherence analysis was carried out in six-channel slides with plasma-treated cyclic olefin copolymer (COC) and poly(tetrafluoro ethylene) (PTFE, as a positive control) substrates as part of the six-channel slides in the absence of EC and under static conditions. PLT activation and aggregation were analyzed using light transmission aggregometry and flow cytometry (CD62P). Medium supplements had no effect on PLT activation and aggregation. In contrast, supplements differentially affected PLT adherence, however, in a polymer- and donor-dependent manner. Thus, the use of standard endothelial growth medium (BM + all supplements) maintains functionality of PLT under EC compatible conditions without masking the differences of PLT adherence on different polymeric substrates. These findings are important prerequisites for the establishment of a near-physiological in vitro thrombogenicity test system assessing polymer-based cardiovascular implant materials in contact with EC and PLT.}, language = {en} } @article{LauGossenLendleinetal.2022, author = {Lau, Skadi and Gossen, Manfred and Lendlein, Andreas and Jung, Friedrich}, title = {Differential sensitivity of assays for determining vein endothelial cell senescence}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {81}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {3}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-211294}, pages = {191 -- 203}, year = {2022}, abstract = {In vivo endothelialization of polymer-based cardiovascular implant materials is a promising strategy to reduce the risk of platelet adherence and the subsequent thrombus formation and implant failure. However, endothelial cells from elderly patients are likely to exhibit a senescent phenotype that may counteract endothelialization. The senescence status of cells should therefore be investigated prior to implantation of devices designed to be integrated in the blood vessel wall. Here, human umbilical vein endothelial cells (HUVEC) were cultivated up to passage (P) 4, 10 and 26/27 to determine the population doubling time and the senescence status by four different methods. Determination of the senescence-associated beta-galactosidase activity (SA-beta-Gal) was carried out by colorimetric staining and microscopy (i), as well as by photometric quantification (ii), and the expression of senescence-associated nuclear proteins p16 and p21 as well as the proliferation marker Ki67 was assessed by immunostaining (iii), and by flow cytometry (iv). The population doubling time of P27-cells was remarkably greater (103 +/- 65 h) compared to P4-cells (24 +/- 3 h) and P10-cell (37 +/- 15 h). Among the four different methods tested, the photometric SA-beta-Gal activity assay and the flow cytometric determination of p16 and Ki67 were most effective in discriminating P27-cells from P4- and P10-cells. These methods combined with functional endothelial cell analyses might aid predictions on the performance of implant endothelialization in vivo.}, language = {en} } @article{ZhangRešetičBehletal.2021, author = {Zhang, Pengfei and Rešetič, Andraž and Behl, Marc and Lendlein, Andreas}, title = {Multifunctionality in polymer networks by dynamic of coordination bonds}, series = {Macromolecular chemistry and physics}, volume = {222}, journal = {Macromolecular chemistry and physics}, number = {3}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1521-3935}, doi = {10.1002/macp.202000394}, pages = {11}, year = {2021}, abstract = {The need for multifunctional materials is driven by emerging technologies and innovations, such as in the field of soft robotics and tactile or haptic systems, where minimizing the number of operational components is not only desirable, but can also be essential for realizing such devices. This study report on designing a multifunctional soft polymer material that can address a number of operating requirements such as solvent resistance, reshaping ability, self-healing capability, fluorescence stimuli-responsivity, and anisotropic structural functions. The numerous functional abilities are associated to rhodium(I)-phosphine coordination bonds, which in a polymer network act with their dynamic and non-covalently bonded nature as multifunctional crosslinks. Reversible aggregation of coordination bonds leads to changes in fluorescence emission intensity that responds to chemical or mechanical stimuli. The fast dynamics and diffusion of rhodium-phosphine ions across and through contacting areas of the material provide for reshaping and self-healing abilities that can be further exploited for assembly of multiple pieces into complex forms, all without any loss to material-sensing capabilities.}, language = {en} } @article{TartivelBlockiBrauneetal.2022, author = {Tartivel, Lucile and Blocki, Anna M. and Braune, Steffen and Jung, Friedrich and Behl, Marc and Lendlein, Andreas}, title = {An Inverse shape-memory hydrogel scaffold switching upon cooling in a tissue-tolerated temperature range}, series = {Advanced materials interfaces}, volume = {9}, journal = {Advanced materials interfaces}, number = {6}, publisher = {Wiley}, address = {Hoboken}, issn = {2196-7350}, doi = {10.1002/admi.202101588}, pages = {9}, year = {2022}, abstract = {Tissue reconstruction has an unmet need for soft active scaffolds that enable gentle loading with regeneration-directing bioactive components by soaking up but also provide macroscopic dimensional stability. Here microporous hydrogels capable of an inverse shape-memory effect (iSME) are described, which in contrast to classical shape-memory polymers (SMPs) recover their permanent shape upon cooling. These hydrogels are designed as covalently photo cross-linked polymer networks with oligo(ethylene glycol)-oligo(propylene glycol)-oligo(ethylene glycol) (OEG-OPG-OEG) segments. When heated after deformation, the OEG-OPG-OEG segments form micelles fixing the temporary shape. Upon cooling, the micelles dissociate again, the deformation is reversed and the permanent shape is obtained. Applicability of this iSME is demonstrated by the gentle loading of platelet-rich plasma (PRP) without causing any platelet activation during this process. PRP is highly bioactive and is widely acknowledged for its regenerative effects. Hence, the microporous inverse shape-memory hydrogel (iSMH) with a cooling induced pore-size effect represents a promising candidate scaffold for tissue regeneration for potential usage in minimally invasive surgery applications.}, language = {en} } @article{MachatschekHeuchelLendlein2021, author = {Machatschek, Rainhard Gabriel and Heuchel, Matthias and Lendlein, Andreas}, title = {Hydrolytic stability of polyetherimide investigated in ultrathin films}, series = {Journal of materials research : JMR / Materials Research Society}, volume = {36}, journal = {Journal of materials research : JMR / Materials Research Society}, number = {14}, publisher = {Springer}, address = {Berlin}, issn = {0884-2914}, doi = {10.1557/s43578-021-00267-6}, pages = {2987 -- 2994}, year = {2021}, abstract = {Increasing the surface hydrophilicity of polyetherimide (PEI) through partial hydrolysis of the imide groups while maintaining the length of the main-chain was explored for adjusting its function in biomedical and membrane applications. The outcome of the polymer analogous reaction, i.e., the degree of ring opening and chain cleavage, is difficult to address in bulk and microstructured systems, as these changes only occur at the interface. Here, the reaction was studied at the air-water interface using the Langmuir technique, assisted by atomic force microscopy and vibrational spectroscopy. Slow PEI hydrolysis sets in at pH > 12. At pH = 14, the ring opening is nearly instantaneous. Reduction of the layer viscosity with time at pH = 14 suggested moderate chain cleavage. No hydrolysis was observed at pH = 1. Hydrolyzed PEI films had a much more cohesive structure, suggesting that the nanoporous morphology of PEI can be tuned via hydrolysis.}, language = {en} } @article{MachatschekHeuchelLendlein2021, author = {Machatschek, Rainhard Gabriel and Heuchel, Matthias and Lendlein, Andreas}, title = {Thin-layer studies on surface functionalization of polyetherimide}, series = {Journal of materials research : JMR / Materials Research Society}, volume = {37}, journal = {Journal of materials research : JMR / Materials Research Society}, number = {1}, publisher = {Springer}, address = {Berlin}, issn = {0884-2914}, doi = {10.1557/s43578-021-00339-7}, pages = {67 -- 76}, year = {2021}, abstract = {Among the high-performance and engineering polymers, polyimides and the closely related polyetherimide (PEI) stand out by their capability to react with nucleophiles under relatively mild conditions. By targeting the phthalimide groups in the chain backbone, post-functionalization offers a pathway to adjust surface properties such as hydrophilicity, solvent resistance, and porosity. Here, we use ultrathin PEI films on a Langmuir trough as a model system to investigate the surface functionalization with ethylene diamine and tetrakis(4-aminophenyl)porphyrin as multivalent nucleophiles. By means of AFM, Raman spectroscopy, and interfacial rheology, we show that hydrolysis enhances the chemical and mechanical stability of ultrathin films and allows for the formation of EDC/NHS-activated esters. Direct amidation of PEI was achieved in the presence of a Lewis acid catalyst, resulting in free amine groups rather than cross-linking. When comparing amidation with hydrolysis, we find a greater influence of the latter on material properties.}, language = {en} } @article{ZhangLiuMachatscheketal.2022, author = {Zhang, Shanshan and Liu, Yue and Machatschek, Rainhard Gabriel and Lendlein, Andreas}, title = {Ultrathin collagen type I films formed at the air-water interface}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {7}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, number = {4}, publisher = {Springer Nature Switzerland AG}, address = {Cham}, issn = {2059-8521}, doi = {10.1557/s43580-021-00160-8}, pages = {56 -- 62}, year = {2022}, abstract = {Collagen-based biomaterials with oriented fibrils have shown great application potential in medicine. However, it is still challenging to control the type I collagen fibrillogenesis in ultrathin films. Here, we report an approach to produce cohesive and well-organized type I collagen ultrathin films of about 10 nm thickness using the Langmuir-Blodgett technique. Ellipsometry, rheology, and Brewster angle microscopy are applied to investigate in situ how the molecules behave at the air-water interface, both at room temperature and 37 degrees C. The interfacial storage modulus observed at room temperature vanishes upon heating, indicating the existence and disappearance of the network structure in the protein nanosheet. The films were spanning over holes as large as 1 mm diameter when transferred at room temperature, proving the strong cohesive interactions. A highly aligned and fibrillar structure was observed by atomic force microscopy (AFM) and optical microscopy.}, language = {en} } @article{ZhangBehlBalketal.2020, author = {Zhang, Pengfei and Behl, Marc and Balk, Maria and Peng, Xingzhou and Lendlein, Andreas}, title = {Shape-programmable architectured hydrogels sensitive to ultrasound}, series = {Macromolecular rapid communications}, volume = {41}, journal = {Macromolecular rapid communications}, number = {7}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1022-1336}, doi = {10.1002/marc.201900658}, pages = {7}, year = {2020}, abstract = {On-demand motion of highly swollen polymer systems can be triggered by changes in pH, ion concentrations, or by heat. Here, shape-programmable, architectured hydrogels are introduced, which respond to ultrasonic-cavitation-based mechanical forces (CMF) by directed macroscopic movements. The concept is the implementation and sequential coupling of multiple functions (swellability in water, sensitivity to ultrasound, shape programmability, and shape-memory) in a semi-interpenetrating polymer network (s-IPN). The semi-IPN-based hydrogels are designed to function through rhodium coordination (Rh-s-IPNH). These coordination bonds act as temporary crosslinks. The porous hydrogels with coordination bonds (degree of swelling from 300 +/- 10 to 680 +/- 60) exhibit tensile strength sigma(max) up to 250 +/- 60 kPa. Shape fixity ratios up to 90\% and shape recovery ratios up to 94\% are reached. Potential applications are switches or mechanosensors.}, language = {en} } @article{BehlBalkLuetzowetal.2021, author = {Behl, Marc and Balk, Maria and L{\"u}tzow, Karola and Lendlein, Andreas}, title = {Impact of block sequence on the phase morphology of multiblock copolymers obtained by high-throughput robotic synthesis}, series = {European polymer journal : EPJ}, volume = {143}, journal = {European polymer journal : EPJ}, publisher = {Elsevier}, address = {Oxford}, issn = {0014-3057}, doi = {10.1016/j.eurpolymj.2020.110207}, pages = {9}, year = {2021}, abstract = {The chemical nature, the number length of integrated building blocks, as well as their sequence structure impact the phase morphology of multiblock copolymers (MBC) consisting of two non-miscible block types. We hypothesized that a strictly alternating sequence should favour phase segregation and in this way the elastic properties. A library of well-defined MBCs composed of two different hydrophobic, semi-crystalline blocks providing domains with well-separated melting temperatures (T(m)s) were synthesized from the same type of precursor building blocks as strictly alternating (MBCsalt) or random (MBCsran) MBCs and compared. Three different series of MBCsalt or MBCsran were synthesized by high-throughput synthesis by coupling oligo(e-caprolactone) (OCL) of different molecular weights (2, 4, and 8 kDa) with oligotetrahydrofuran (OTHF, 2.9 kDa) via Steglich esterification in which the molar ratio of the reaction partners was slightly adjusted. Maximum of weight average molecular weight (M-w) were 65,000 g center dot mol(-1), 165,000 g center dot mol(-1), and 168,000 g center dot mol(-1) for MBCsalt and 80,500 g center dot mol(-1), 100,000 g center dot mol(-1), and 147,600 g center dot mol(-1) for MBCsran. When Mw increased, a decrease of both Tms associated to the melting of the OCL and OTHF domains was observed for all MBCs. T-m (OTHF) of MBCsran was always higher than Tm (OTHF) of MBCsalt, which was attributed to a better phase segregation. In addition, the elongation at break of MBCsalt was almost half as high when compared to MBCsran. In this way this study elucidates role of the block length and sequence structure in MBCs and enables a quantitative discussion of the structure-function relationship when two semi-crystalline block segments are utilized for the design of block copolymers.}, language = {en} } @article{MachatschekLendlein2019, author = {Machatschek, Rainhard Gabriel and Lendlein, Andreas}, title = {Fundamental insights in PLGA degradation from thin film studies}, series = {Journal of controlled release : official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems}, volume = {319}, journal = {Journal of controlled release : official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems}, publisher = {Elsevier}, address = {New York}, issn = {0168-3659}, doi = {10.1016/j.jconrel.2019.12.044}, pages = {276 -- 284}, year = {2019}, abstract = {Poly(lactide-co-glycolide)s are commercially available degradable implant materials, which are typically selected based on specifications given by the manufacturer, one of which is their molecular weight. Here, we address the question whether variations in the chain length and their distribution affect the degradation behavior of Poly[(rac-lactide)-co-glycolide]s (PDLLGA). The hydrolysis was studied in ultrathin films at the air-water interface in order to rule out any morphological effects. We found that both for purely hydrolytic degradation as well as under enzymatic catalysis, the molecular weight has very little effect on the overall degradation kinetics of PDLLGAs. The quantitative analysis suggested a random scission mechanism. The monolayer experiments showed that an acidic micro-pH does not accelerate the degradation of PDLLGAs, in contrast to alkaline conditions. The degradation experiments were combined with interfacial rheology measurements, which showed a drastic decrease of the viscosity at little mass loss. The extrapolated molecular weight behaved similar to the viscosity, dropping to a value near to the solubility limit of PDLLGA oligomers before mass loss set in. This observation suggests a solubility controlled degradation of PDLLGA. Conclusively, the molecular weight affects the degradation of PDLLGA devices mostly in indirect ways, e.g. by determining their morphology and porosity during fabrication. Our study demonstrates the relevance of the presented Langmuir degradation method for the design of controlled release systems.}, language = {en} } @article{FriessLendleinWischke2021, author = {Frieß, Fabian and Lendlein, Andreas and Wischke, Christian}, title = {Switching microobjects from low to high aspect ratios using a shape-memory effect}, series = {Soft matter}, volume = {17}, journal = {Soft matter}, number = {41}, publisher = {Royal Society of Chemistry}, address = {London}, issn = {1744-6848}, doi = {10.1039/d1sm00947h}, pages = {9326 -- 9331}, year = {2021}, abstract = {Spherical particles from shape-memory polymers (SMP) can be stretched to ellipsoids with high aspect ratio (AR) and temporarily stabilized. They can switch back to low AR upon thermal stimulation. Here, the creation of an alternative shape-switching capability of particles from low to high AR is introduced, where a SMP matrix from polyvinyl alcohol (PVA) is used to create crosslinked high AR particles and to program the embedded micrometer-sized particles from a second SMP (oligo(epsilon-caprolactone) micronetworks, MN) with a low switching temperature T-sw. This programming proceeds through shape-recovery of the PVA matrix, from which the MN are harvested by PVA matrix dissolution. The use of a dissolvable SMP matrix may be a general strategy to efficiently create systems with complex moving capabilities.}, language = {en} } @article{LauGossenLendlein2021, author = {Lau, Skadi and Gossen, Manfred and Lendlein, Andreas}, title = {Designing cardiovascular implants taking in view the endothelial basement membrane}, series = {International journal of molecular sciences}, volume = {22}, journal = {International journal of molecular sciences}, number = {23}, publisher = {MDPI}, address = {Basel}, issn = {1422-0067}, doi = {10.3390/ijms222313120}, pages = {26}, year = {2021}, abstract = {Insufficient endothelialization of cardiovascular grafts is a major hurdle in vascular surgery and regenerative medicine, bearing a risk for early graft thrombosis. Neither of the numerous strategies pursued to solve these problems were conclusive. Endothelialization is regulated by the endothelial basement membrane (EBM), a highly specialized part of the vascular extracellular matrix. Thus, a detailed understanding of the structure-function interrelations of the EBM components is fundamental for designing biomimetic materials aiming to mimic EBM functions. In this review, a detailed description of the structure and functions of the EBM are provided, including the luminal and abluminal interactions with adjacent cell types, such as vascular smooth muscle cells. Moreover, in vivo as well as in vitro strategies to build or renew EBM are summarized and critically discussed. The spectrum of methods includes vessel decellularization and implant biofunctionalization strategies as well as tissue engineering-based approaches and bioprinting. Finally, the limitations of these methods are highlighted, and future directions are suggested to help improve future design strategies for EBM-inspired materials in the cardiovascular field.}, language = {en} } @article{BalkBehlNoecheletal.2021, author = {Balk, Maria and Behl, Marc and N{\"o}chel, Ulrich and Lendlein, Andreas}, title = {Enzymatically triggered Jack-in-the-box-like hydrogels}, series = {ACS applied materials \& interfaces / American Chemical Society}, volume = {13}, journal = {ACS applied materials \& interfaces / American Chemical Society}, number = {7}, publisher = {American Chemical Society}, address = {Washington, DC}, issn = {1944-8244}, doi = {10.1021/acsami.1c00466}, pages = {8095 -- 8101}, year = {2021}, abstract = {Enzymes can support the synthesis or degradation of biomacromolecules in natural processes. Here, we demonstrate that enzymes can induce a macroscopic-directed movement of microstructured hydrogels following a mechanism that we call a "Jack-in-the-box" effect. The material's design is based on the formation of internal stresses induced by a deformation load on an architectured microscale, which are kinetically frozen by the generation of polyester locking domains, similar to a Jack-in-thebox toy (i.e., a compressed spring stabilized by a closed box lid). To induce the controlled macroscopic movement, the locking domains are equipped with enzyme-specific cleavable bonds (i.e., a box with a lock and key system). As a result of enzymatic reaction, a transformed shape is achieved by the release of internal stresses. There is an increase in entropy in combination with a swelling-supported stretching of polymer chains within the microarchitectured hydrogel (i.e., the encased clown pops-up with a pre-stressed movement when the box is unlocked). This utilization of an enzyme as a physiological stimulus may offer new approaches to create interactive and enzyme-specific materials for different applications such as an optical indicator of the enzyme's presence or actuators and sensors in biotechnology and in fermentation processes.}, language = {en} } @article{LoewenbergTripodoJulichGruneretal.2020, author = {L{\"o}wenberg, Candy and Tripodo, Giuseppe and Julich-Gruner, Konstanze K. and Neffe, Axel T. and Lendlein, Andreas}, title = {Supramolecular gelatin networks based on inclusion complexes}, series = {Macromolecular bioscience}, volume = {20}, journal = {Macromolecular bioscience}, number = {10}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1616-5187}, doi = {10.1002/mabi.202000221}, pages = {8}, year = {2020}, abstract = {Hydrogel forming physical networks based on gelatin are an attractive approach toward multifunctional biomaterials with the option of reshaping, self-healing, and stimuli-sensitivity. However, it is challenging to design such gelatin-based hydrogels to be stable at body temperature. Here, gelatin functionalized with desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) side chains is crosslinked with cyclodextrin (CD) dimers under formation of inclusions complexes. The supramolecular networks displayed at room temperature decreased water uptake (200-600 wt\% for DAT-based systems, 200 wt\% for DATT based systems), and increased storage moduli up to 25.6 kPa determined by rheology compared to DAT(T) gelatin. The gel-sol transition temperature increased from 33 up to 42 degrees C. The presented system that is completely based on natural building blocks may form the basis for materials that may potentially respond by dissolution or changes of properties to changes in environmental conditions or to the presence of CD guest molecules.}, language = {en} } @article{FolikumahBehlLendlein2021, author = {Folikumah, Makafui Yao and Behl, Marc and Lendlein, Andreas}, title = {Thiol-Thioester exchange reactions in precursors enable pH-triggered hydrogel formation}, series = {Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences}, volume = {22}, journal = {Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences}, number = {5}, publisher = {American Chemical Society}, address = {Washington}, issn = {1525-7797}, doi = {10.1021/acs.biomac.0c01690}, pages = {1875 -- 1884}, year = {2021}, abstract = {Bio-interactive hydrogel formation in situ requires sensory capabilities toward physiologically relevant stimuli. Here, we report on pH-controlled in situ hydrogel formation relying on latent cross-linkers, which transform from pH sensors to reactive molecules. In particular, thiopeptolide/thio-depsipeptides were capable of pH-sensitive thiol-thioester exchange reactions to yield a,co-dithiols, which react with maleimide-functionalized multi-arm polyethylene glycol to polymer networks. Their water solubility and diffusibility qualify thiol/thioester-containing peptide mimetics as sensory precursors to drive in situ localized hydrogel formation with potential applications in tissue regeneration such as treatment of inflamed tissues of the urinary tract.}, language = {en} } @article{FriessLendleinWischke2021, author = {Friess, Fabian and Lendlein, Andreas and Wischke, Christian}, title = {Size control of shape switchable micronetworks by fast two-step microfluidic templating}, series = {Journal of materials research}, volume = {36}, journal = {Journal of materials research}, number = {16}, publisher = {Springer}, address = {Berlin}, issn = {0884-2914}, doi = {10.1557/s43578-021-00295-2}, pages = {3248 -- 3257}, year = {2021}, abstract = {Shape-memory polymer micronetworks (MN) are micrometer-sized objects that can switch their outer shape upon external command.This study aims to scale MN sizes to the low micrometer range at very narrow size distributions. In a two-step microfluidic strategy, the specific design of coaxial class capillary devices allowed stabilizing the thread of the dispersed phase to efficiently produce precursor particles in the tip-streaming regime at rates up to similar to 170 kHz and final sizes down to 4 mu m. In a subsequent melt-based microfluidic photocrosslinking of the methacrylate-functionalized oligo(epsilon-caprolactone) precursor material, MN could be produced without particle aggregation. A comprehensive analysis of MN properties illustrated successful crosslinking, semi-crystalline morphology, and a shape-switching functionality for all investigated MN sizes (4, 6, 9, 12, 22 mu m). Such functional micronetworks tailored to and below the dimension of cells can enable future applications in technology and medicine like controlling cell interaction.}, language = {en} } @article{LiangBehlLendlein2021, author = {Liang, Xiao and Behl, Marc and Lendlein, Andreas}, title = {Dihydroxy terminated teroligomers from morpholine-2,5-diones}, series = {European polymer journal : EPJ}, volume = {143}, journal = {European polymer journal : EPJ}, publisher = {Elsevier}, address = {Oxford}, issn = {0014-3057}, doi = {10.1016/j.eurpolymj.2020.110189}, pages = {9}, year = {2021}, abstract = {Oligodepsipeptides (ODPs) attract increasing attention as degradable materials in controlled drug delivery or as building blocks for nano-carriers. Their strong intermolecular interactions provide high stability. Tailoring the side groups of the amino acid repeating units to achieve a strong affinity to particular drugs allows a high drug-loading capacity. Here we describe synthesis and characterization of dihydroxy terminated teroligodepsipeptides (ter-ODPs) by ring-opening copolymerization (ROP) of three different morpholine-2,5-diones (MDs) in bulk in order to provide a set of teroligomers with structural variation for drug release or transfection. Ter-ODPs with equivalent co-monomer feed ratios were prepared as well as ter-ODPs, in which the co-monomer feed ratio was varied between 9 mol\% and 78 mol\%. Ter-ODPs were synthesized by ROP using 1,1,10,10-tetra-n-butyl-1,10-distanna-2,9,11,18-tetraoxa-5,6,14,15-tetrasulfur-cyclodecane (tin(IV) alkoxide) that was obtained by the reaction of dibutyl tin(II) oxide with 2-hydroxyethyl disulfide. The number average molecular weight (M-n) of ter-ODPs, determined by H-1 NMR and gel permeation chromatography (GPC), ranged between 4000 g center dot mol(-1) and 8600 g center dot mol(-1). Co-monomer compositions in ter-ODPs could be controlled by changing the feed ratio of co-monomers as observed by H-1 NMR spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The amount of remaining monomers as determined by H-1 NMR could be kept below 1 wt\%. Macrocycles as main sources of byproducts as determined from MALDI-TOF-MS measurements were significantly lower as compared to polymerization by Sn(Oct)(2). Glass-transition temperature (T-g) of ter-ODPs ranged between 59 degrees C and 70 degrees C.}, language = {en} } @article{LuetzowWeigelLendlein2020, author = {L{\"u}tzow, Karola and Weigel, Thomas and Lendlein, Andreas}, title = {Solvent-based fabrication method for magnetic, shape-memory nanocomposite foams}, series = {MRS advances}, volume = {5}, journal = {MRS advances}, number = {14-15}, publisher = {Cambridge Univ. Press}, address = {Cambridge}, issn = {2059-8521}, doi = {10.1557/adv.2019.422}, pages = {785 -- 795}, year = {2020}, abstract = {This paper presents shape-memory foams that can be temporarily fixed in their compressed state and be expanded on demand. Highly porous, nanocomposite foams were prepared from a solution of polyetherurethane with suspended nanoparticles (mean aggregate size 90 nm) which have an iron(III) oxide core with a silica shell. The polymer solution with suspended nanoparticles was cooled down to -20 degrees C in a two-stage process, which was followed by freeze-drying. The average pore size increases with decreasing concentration of nanoparticles from 158 mu m to 230 mu m while the foam porosity remained constant. After fixation of a temporary form of the nanocomposite foams, shape recovery can be triggered either by heat or by exposure to an alternating magnetic field. Compressed foams showed a recovery rate of up to 76 +/- 4\% in a thermochamber at 80 degrees C, and a slightly lower recovery rate of up to 65 +/- 4\% in a magnetic field.}, language = {en} } @article{HoffmannMachatschekLendlein2020, author = {Hoffmann, Falk and Machatschek, Rainhard Gabriel and Lendlein, Andreas}, title = {Understanding the impact of crystal lamellae organization on small molecule diffusion using a Monte Carlo approach}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {5}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, number = {52-53}, publisher = {Cambridge University Press}, address = {Cambridge}, issn = {2059-8521}, doi = {10.1557/adv.2020.386}, pages = {2737 -- 2749}, year = {2020}, abstract = {Many physicochemical processes depend on the diffusion of small molecules through solid materials. While crystallinity in polymers is advantageous with respect to structure performance, diffusion in such materials is difficult to predict. Here, we investigate the impact of crystal morphology and organization on the diffusion of small molecules using a lattice Monte Carlo approach. Interestingly, diffusion determined with this model does not depend on the internal morphology of the semi-crystalline regions. The obtained insight is highly valuable for developing predictive models for all processes in semi-crystalline polymers involving mass transport, like polymer degradation or drug release, and provide design criteria for the time-dependent functional behavior of multifunctional polymer systems.}, language = {en} } @article{IzraylitGouldKratzetal.2020, author = {Izraylit, Victor and Gould, Oliver E. C. and Kratz, Karl and Lendlein, Andreas}, title = {Investigating the phase-morphology of PLLA-PCL multiblock copolymer/PDLA blends cross-linked using stereocomplexation}, series = {MRS advances}, volume = {5}, journal = {MRS advances}, number = {14-15}, publisher = {Cambridge Univ. Press}, address = {New York}, issn = {2059-8521}, doi = {10.1557/adv.2019.465}, pages = {699 -- 707}, year = {2020}, abstract = {The macroscale function of multicomponent polymeric materials is dependent on their phase-morphology. Here, we investigate the morphological structure of a multiblock copolymer consisting of poly(L-lactide) and poly(epsilon-caprolactone) segments (PLLA-PCL), physically cross-linked by stereocomplexation with a low molecular weight poly(D-lactide) oligomer (PDLA). The effects of blend composition and PLLA-PCL molecular structure on the morphology are elucidated by AFM, TEM and SAXS. We identify the formation of a lattice pattern, composed of PLA domains within a PCL matrix, with an average domain spacing d0 = 12 - 19 nm. The size of the PLA domains were found to be proportional to the block length of the PCL segment of the copolymer and inversely proportional to the PDLA content of the blend. Changing the PLLA-PCL / PDLA ratio caused a shift in the melt transition Tm attributed to the PLA stereocomplex crystallites, indicating partial amorphous phase dilution of the PLA and PCL components within the semicrystalline material. By elucidating the phase structure and thermal character of multifunctional PLLA-PCL / PDLA blends, we illustrate how composition affects the internal structure and thermal properties of multicomponent polymeric materials. This study should facilitate the more effective incorporation of a variety of polymeric structural units capable of stimuli responsive phase transitions, where an understanding the phase-morphology of each component will enable the production of multifunctional soft-actuators with enhanced performance.}, language = {en} } @article{SauterKratzHeucheletal.2021, author = {Sauter, Tilman and Kratz, Karl and Heuchel, Matthias and Lendlein, Andreas}, title = {Fiber diameter as design parameter for tailoring the macroscopic shape-memory performance of electrospun meshes}, series = {Materials and design}, volume = {202}, journal = {Materials and design}, publisher = {Elsevier}, address = {Amsterdam [u.a.]}, issn = {1873-4197}, doi = {10.1016/j.matdes.2021.109546}, pages = {10}, year = {2021}, abstract = {Fibrous shape-memory polymer (SMP) scaffolds were investigated considering the fiber as basic microstructural feature. By reduction of the fiber diameter in randomly oriented electrospun polyetherurethane (PEU) meshes from the micro-to the nano-scale, we observed changes in the molecular orientation within the fibers and its impact on the structural and shape-memory performance. It was assumed that a spatial restriction by reduction of the fiber diameter increases molecular orientation along the orientation of the fiber. The stress-strain relation of random PEU scaffolds is initially determined by the 3D arrangement of the fibers and thus is independent of the molecular orientation. Increasing the molecular orientation with decreasing single fiber diameter in scaffolds composed of randomly arranged fibers did not alter the initial stiffness and peak stress but strongly influenced the elongation at break and the stress increase above the Yield point. Reduction of the single fiber diameter also distinctly improved the shape-memory performance of the scaffolds. Fibers with nanoscale diameters (< 100 nm) possessed an almost complete shape recovery, high recovery stresses and fast relaxation kinetics, while the shape fixity was found to decrease with decreasing fiber diameter. Hence, the fiber diameter is a relevant design parameter for SMP.}, language = {en} } @article{TarazonaMachatschekLendlein2020, author = {Tarazona, Natalia A. and Machatschek, Rainhard Gabriel and Lendlein, Andreas}, title = {Influence of depolymerases and lipases on the degradation of polyhydroxyalkanoates determined in Langmuir degradation studies}, series = {Advanced materials interfaces}, volume = {7}, journal = {Advanced materials interfaces}, number = {17}, publisher = {Wiley}, address = {Hoboken}, issn = {2196-7350}, doi = {10.1002/admi.202000872}, pages = {9}, year = {2020}, abstract = {Microbially produced polyhydroxyalkanoates (PHAs) are polyesters that are degradable by naturally occurring enzymes. Albeit PHAs degrade slowly when implanted in animal models, their disintegration is faster compared to abiotic hydrolysis under simulated physiological environments. Ultrathin Langmuir-Blodgett (LB) films are used as models for fast in vitro degradation testing, to predict enzymatically catalyzed hydrolysis of PHAs in vivo. The activity of mammalian enzymes secreted by pancreas and liver, potentially involved in biomaterials degradation, along with microbial hydrolases is tested toward LB-films of two model PHAs, poly(3-R-hydroxybutyrate) (PHB) and poly[(3-R-hydroxyoctanoate)-co-(3-R-hydroxyhexanoate)] (PHOHHx). A specific PHA depolymerase fromStreptomyces exfoliatus, used as a positive control, is shown to hydrolyze LB-films of both polymers regardless of their side-chain-length and phase morphology. From amorphous PHB and PHOHHx, approximate to 80\% is eroded in few hours, while mass loss for semicrystalline PHB is 25\%. Surface potential and interfacial rheology measurements show that material dissolution is consistent with a random-chain-scission mechanism. Degradation-induced crystallization of semicrystalline PHB LB-films is also observed. Meanwhile, the surface and the mechanical properties of both LB-films remain intact throughout the experiments with lipases and other microbial hydrolases, suggesting that non-enzymatic hydrolysis could be the predominant factor for acceleration of PHAs degradation in vivo.}, language = {en} } @article{BehlBalkMansfeldetal.2021, author = {Behl, Marc and Balk, Maria and Mansfeld, Ulrich and Lendlein, Andreas}, title = {Phase morphology of multiblock copolymers differing in sequence of blocks}, series = {Macromolecular materials and engineering}, volume = {306}, journal = {Macromolecular materials and engineering}, number = {3}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1439-2054}, doi = {10.1002/mame.202000672}, pages = {9}, year = {2021}, abstract = {The chemical nature, the number length of integrated building blocks, as well as their sequence structure impact the phase morphology of multiblock copolymers (MBC) consisting of two non-miscible block types. It is hypothesized that a strictly alternating sequence should impact phase segregation. A library of well-defined MBC obtained by coupling oligo(epsilon-caprolactone) (OCL) of different molecular weights (2, 4, and 8 kDa) with oligotetrahydrofuran (OTHF, 2.9 kDa) via Steglich esterification results in strictly alternating (MBCalt) or random (MBCran) MBC. The three different series has a weight average molecular weight (M-w) of 65 000, 165 000, and 168 000 g mol(-1) for MBCalt and 80 500, 100 000, and 147 600 g mol(-1) for MBCran. When the chain length of OCL building blocks is increased, the tendency for phase segregation is facilitated, which is attributed to the decrease in chain mobility within the MBC. Furthermore, it is found that the phase segregation disturbs the crystallization by causing heterogeneities in the semi-crystalline alignment, which is attributed to an increase of the disorder of the OCL semi-crystalline alignment.}, language = {en} } @article{DengWangXuetal.2020, author = {Deng, Zijun and Wang, Weiwei and Xu, Xun and Ma, Nan and Lendlein, Andreas}, title = {Modulation of mesenchymal stem cell migration using programmable polymer sheet actuators}, series = {MRS advances}, volume = {5}, journal = {MRS advances}, number = {46-47}, publisher = {Cambridge Univ. Press}, address = {New York}, issn = {2059-8521}, doi = {10.1557/adv.2020.235}, pages = {2381 -- 2390}, year = {2020}, abstract = {Recruitment of mesenchymal stem cells (MSCs) to damaged tissue is a crucial step to modulate tissue regeneration. Here, the migration of human adipose-derived stem cells (hADSCs) responding to thermal and mechanical stimuli was investigated using programmable shape-memory polymer actuator (SMPA) sheets. Changing the temperature repetitively between 10 and 37 degrees C, the SMPA sheets are capable of reversibly changing between two different pre-defined shapes like an artificial muscle. Compared to non-actuating sheets, the cells cultured on the programmed actuating sheets presented a higher migration velocity (0.32 +/- 0.1 vs. 0.57 +/- 0.2 mu m/min). These results could motivate the next scientific steps, for example, to investigate the MSCs pre-loaded in organoids towards their migration potential.}, language = {en} } @article{BehlZhaoLendlein2020, author = {Behl, Marc and Zhao, Qian and Lendlein, Andreas}, title = {Glucose-responsive shape-memory cryogels}, series = {Journal of materials research : JMR}, volume = {35}, journal = {Journal of materials research : JMR}, number = {18}, publisher = {Springer}, address = {Berlin}, issn = {0884-2914}, doi = {10.1557/jmr.2020.204}, pages = {2396 -- 2404}, year = {2020}, abstract = {Boronic ester bonds can be reversibly formed between phenylboronic acid (PBA) and triol moieties. Here, we aim at a glucose-induced shape-memory effect by implementing such bonds as temporary netpoints, which are cleavable by glucose and by minimizing the volume change upon stimulation by a porous cryogel structure. The polymer system consisted of a semi-interpenetrating network (semi-IPN) architecture, in which the triol moieties were part of the permanent network and the PBA moieties were located in the linear polymer diffused into the semi-IPN. In an alkaline medium (pH = 10), the swelling ratio was approximately 35, independent of C-glu varied between 0 and 300 mg/dL. In bending experiments, shape fixity R-f approximate to 80\% and shape recovery R-r approximate to 100\% from five programming/recovery cycles could be determined. R-r was a function of C-glu in the range from 0 to 300 mg/dL, which accords with the fluctuation range of C-glu in human blood. In this way, the shape-memory hydrogels could play a role in future diabetes treatment options.}, language = {en} } @article{LendleinHeuchel2021, author = {Lendlein, Andreas and Heuchel, Matthias}, title = {Shape-memory polymers designed in view of thermomechanical energy storage and conversion systems}, series = {ACS central science}, volume = {7}, journal = {ACS central science}, number = {10}, publisher = {American Chemical Society}, address = {Washington}, issn = {2374-7951}, doi = {10.1021/acscentsci.1c01032}, pages = {1599 -- 1601}, year = {2021}, language = {en} } @article{BalkBehlLendlein2020, author = {Balk, Maria and Behl, Marc and Lendlein, Andreas}, title = {Actuators based on oligo[(epsilon-caprolactone)-co-glycolide] with accelerated hydrolytic degradation}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {5}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, number = {12-13}, publisher = {Cambridge University Press}, address = {New York, NY}, issn = {2059-8521}, doi = {10.1557/adv.2019.447}, pages = {655 -- 666}, year = {2020}, abstract = {Polyester-based shape-memory polymer actuators are multifunctional materials providing reversible macroscopic shape shifts as well as hydrolytic degradability. Here, the function-function interdependencies (between shape shifts and degradation behaviour) will determine actuation performance and its life time. In this work, glycolide units were incorporated in poly(epsilon-caprolactone) based actuator materials in order to achieve an accelerated hydrolytic degradation and to explore the function-function relationship. Three different oligo[(epsilon-caprolactone)-co-glycolide] copolymers (OCGs) with similar molecular weights (10.5 +/- 0.5 kg center dot mol(-1)) including a glycolide content of 8, 16, and 26 mol\% (ratio 1:1:1 wt\%) terminated with methacrylated moieties were crosslinked. The obtained actuators provided a broad melting transition in the range from 27 to 44 degrees C. The hydrolytic degradation of programmed OCG actuators (200\% of elongation) resulted in a reduction of sample mass to 51 wt\% within 21 days at pH = 7.4 and 40 degrees C. Degradation results in a decrease of T-m associated to the actuating units and increasing T-m associated to the skeleton forming units. The actuation capability decreased almost linear as function of time. After 11 days of hydrolytic degradation the shape-memory functionality was lost. Accordingly, a fast degradation behaviour as required, e.g., for actuator materials intended as implant material can be realized.}, language = {en} } @article{LiangBehlLuetzowetal.2021, author = {Liang, Xiao and Behl, Marc and L{\"u}tzow, Karola and Lendlein, Andreas}, title = {Cooligomers from morpholine-2,5-dione and para-dioxanone and catalyst complex SnOct(2)/2-hydroxyethyl sulfide}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {6}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, number = {32}, publisher = {Springer}, address = {Heidelberg}, issn = {2059-8521}, doi = {10.1557/s43580-021-00082-5}, pages = {764 -- 768}, year = {2021}, abstract = {Complexes from catalysts and initiator can be used to insert a specific number of additional chemical functional groups in (co)polymers prepared by ring-opening polymerization (ROP) of lactones. We report on the synthesis of cooligomers from sec-butyl-morpholine-2,5-dione (SBMD) and para-dioxanone (PDX) by ROP with varied feed ratios in the bulk using the catalyst complex SnOct(2)/2-hydroxyethyl sulfide. M-n of the cooligomers (determined by GPC) decreased with decreasing SBMD feed ratio from 4200 +/- 420 to 800 +/- 80 g mol(-1). When the feed ratio was reduced from 80 to 50 mol\% the molar ratio of SBMD of the cooligomers (determined by H-1-NMR) remained nearly unchanged between 81 and 86 mol\% and was attributed to a higher reactivity of SBMD. This assumption was confirmed by fractionation of GPC, in which an increase of SBMD with increasing molecular weight was observed. The catalyst/initiator system provides a high potential to create orthogonal building blocks by cleavage of the sulfide bond.}, language = {en} } @article{IzraylitHommesSchattmannNeffeetal.2020, author = {Izraylit, Victor and Hommes-Schattmann, Paul J. and Neffe, Axel T. and Gould, Oliver E. C. and Lendlein, Andreas}, title = {Polyester urethane functionalizable through maleimide side-chains and cross-linkable by polylactide stereocomplexes}, series = {European polymer journal}, volume = {137}, journal = {European polymer journal}, publisher = {Elsevier}, address = {Oxford}, issn = {0014-3057}, doi = {10.1016/j.eurpolymj.2020.109916}, pages = {8}, year = {2020}, abstract = {Sustainable multifunctional alternatives to fossil-derived materials, which can be functionalized and are degradable, can be envisioned by combining naturally derived starting materials with an established polymer design concept. Modularity and chemical flexibility of polyester urethanes (PEU) enable the combination of segments bearing functionalizable moieties and the tailoring of the mechanical and thermal properties. In this work, a PEU multiblock structure was synthesized from naturally derived L-lysine diisocyanate ethyl ester (LDI), poly(L-lactide) diol (PLLA) and N-(2,3-dihydroxypropyl)-maleimide (MID) in a one-step reaction. A maleimide side-chain (MID) provided a reactive site for the catalyst-free coupling of thiols shown for L-cysteine with a yield of 94\%. Physical cross-links were generated by blending the PEU with poly(D-lactide) (PDLA), upon which the PLLA segments of the PEU and the PDLA formed stereocomplexes. Stereocomplexation occurred spontaneously during solution casting and was investigated with WAXS and DSC. Stereocomplex crystallites were observed in the blends, while isotactic PLA crystallization was not observed. The presented material platform with tailorable mechanical properties by blending is of specific interest for engineering biointerfaces of implants or carrier systems for bioactive molecules.}, language = {en} } @article{IzraylitHommesSchattmannNeffeetal.2020, author = {Izraylit, Victor and Hommes-Schattmann, Paul Jacob and Neffe, Axel T. and Gould, Oliver E. C. and Lendlein, Andreas}, title = {Alkynyl-functionalized chain-extended PCL for coupling to biological molecules}, series = {European polymer journal}, volume = {136}, journal = {European polymer journal}, publisher = {Elsevier}, address = {Oxford}, issn = {0014-3057}, doi = {10.1016/j.eurpolymj.2020.109908}, pages = {11}, year = {2020}, abstract = {Chemical functionalization of poly(epsilon-caprolactone) (PCL) enables a molecular integration of additional function. Here, we report an approach to incorporate reactive alkynyl side-groups by synthesizing a chain-extended PCL, where the reactive site is introduced through the covalently functionalizable chain extender 3 (prop-2-yn-1-yloxy)propane-1,2-diol (YPD). Chain-extended PCL with M-w of 101 to 385 kg.mol(-1) were successfully synthesized in a one-pot reaction from PCL-diols with various molar masses, L-lysine ethyl ester diisocyanate (LDI) or trimethyl(hexamethylene)diisocyanate (TMDI), and YPD, in which the density of functionalizable groups and spacing between them can be controlled by the composition of the polymer. The employed diisocyanate compounds and YPD possess an asymmetric structure and form a non-crystallizable segment leaving the PCL crystallites to dominate the material's mechanical properties. The mixed glass transition temperature T-g = - 60 to - 46 degrees C of the PCL/polyurethane amorphous phase maintains the synthesized materials in a highly elastic state at ambient and physiological conditions. Reaction conditions for covalent attachment in copper(I)-catalyzed azide-alkyne-cycloaddition reactions (CuAAC) in solution were optimized in a series of model reactions between the alkyne moieties of the chain-extended PCL and benzyl azide, reaching conversions over 95\% of the alkyne moieties and with yields of up to 94\% for the purified functionalized PCL. This methodology was applied for reaction with the azide-functionalized cell adhesion peptide GRGDS. The required modification of the peptide provides selectivity in the coupling reactions. The obtained results suggest that YPD could potentially be employed as versatile molecular unit for the creation of a variety of functionalizable polyesters as well as polyurethanes and polycarbonates offering efficient and selective click-reactions.}, language = {en} } @article{LiuGouldKratzetal.2022, author = {Liu, Yue and Gould, Oliver E. C. and Kratz, Karl and Lendlein, Andreas}, title = {On demand sequential release of (sub)micron particles controlled by size and temperature}, series = {Small : nano micro}, volume = {18}, journal = {Small : nano micro}, number = {5}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1613-6810}, doi = {10.1002/smll.202104621}, pages = {8}, year = {2022}, abstract = {Polymeric devices capable of releasing submicron particles (subMP) on demand are highly desirable for controlled release systems, sensors, and smart surfaces. Here, a temperature-memory polymer sheet with a programmable smooth surface served as matrix to embed and release polystyrene subMP controlled by particle size and temperature. subMPs embedding at 80 degrees C can be released sequentially according to their size (diameter D of 200 nm, 500 nm, 1 mu m) when heated. The differences in their embedding extent are determined by the various subMPs sizes and result in their distinct release temperatures. Microparticles of the same size (D approximate to 1 mu m) incorporated in films at different programming temperatures T-p (50, 65, and 80 degrees C) lead to a sequential release based on the temperature-memory effect. The change of apparent height over the film surface is quantified using atomic force microscopy and the realization of sequential release is proven by confocal laser scanning microscopy. The demonstration and quantification of on demand subMP release are of technological impact for assembly, particle sorting, and release technologies in microtechnology, catalysis, and controlled release.}, language = {en} } @article{MoradianGossenLendlein2022, author = {Moradian, Hanieh and Gossen, Manfred and Lendlein, Andreas}, title = {Co-delivery of genes can be confounded by bicistronic vector design}, series = {MRS Communications}, volume = {12}, journal = {MRS Communications}, number = {2}, publisher = {Springer}, address = {Heidelberg}, issn = {2159-6859}, doi = {10.1557/s43579-021-00128-7}, pages = {145 -- 153}, year = {2022}, abstract = {Maximizing the efficiency of nanocarrier-mediated co-delivery of genes for co-expression in the same cell is critical for many applications. Strategies to maximize co-delivery of nucleic acids (NA) focused largely on carrier systems, with little attention towards payload composition itself. Here, we investigated the effects of different payload designs: co-delivery of two individual "monocistronic" NAs versus a single bicistronic NA comprising two genes separated by a 2A self-cleavage site. Unexpectedly, co-delivery via the monocistronic design resulted in a higher percentage of co-expressing cells, while predictive co-expression via the bicistronic design remained elusive. Our results will aid the application-dependent selection of the optimal methodology for co-delivery of genes.}, language = {en} } @article{BehlRazzaqMazurekBudzynskaetal.2020, author = {Behl, Marc and Razzaq, Muhammad Yasar and Mazurek-Budzynska, Magdalena and Lendlein, Andreas}, title = {Polyetheresterurethane based porous scaffolds with tailorable architectures by supercritical CO2 foaming}, series = {MRS advances}, volume = {5}, journal = {MRS advances}, number = {45}, publisher = {Cambridge University Press}, address = {New York, NY}, issn = {2059-8521}, doi = {10.1557/adv.2020.345}, pages = {2317 -- 2330}, year = {2020}, abstract = {Porous three-dimensional (3D) scaffolds are promising treatment options in regenerative medicine. Supercritical and dense-phase fluid technologies provide an attractive alternative to solvent-based scaffold fabrication methods. In this work, we report on the fabrication of poly-etheresterurethane (PPDO-PCL) based porous scaffolds with tailorable pore size, porosity, and pore interconnectivity by using supercritical CO2(scCO(2)) fluid-foaming. The influence of the processing parameters such as soaking time, soaking temperature and depressurization on porosity, pore size, and interconnectivity of the foams were investigated. The average pore diameter could be varied between 100-800 mu m along with a porosity in the range from (19 +/- 3 to 61 +/- 6)\% and interconnectivity of up to 82\%. To demonstrate their applicability as scaffold materials, selected foams were sterilized via ethylene oxide sterilization. They showed negligible cytotoxicity in tests according to DIN EN ISO 10993-5 and 10993-12 using L929 cells. The study demonstrated that the pore size, porosity and the interconnectivity of this multi-phase semicrystalline polymer could be tailored by careful control of the processing parameters during the scCO(2)foaming process. In this way, PPDO-PCL scaffolds with high porosity and interconnectivity are potential candidate materials for regenerative treatment options.}, language = {en} } @article{LiuGouldKratzetal.2020, author = {Liu, Yue and Gould, Oliver E. C. and Kratz, Karl and Lendlein, Andreas}, title = {Shape-memory actuation of individual micro-/nanofibers}, series = {MRS Advances}, volume = {5}, journal = {MRS Advances}, number = {46-47}, publisher = {Cambridge Univ. Press}, address = {New York}, issn = {2059-8521}, doi = {10.1557/adv.2020.276}, pages = {2391 -- 2399}, year = {2020}, abstract = {Advances in the fabrication and characterization of polymeric nanomaterials has greatly advanced the miniaturization of soft actuators, creating materials capable of replicating the functional physical behavior previously limited to the macroscale. Here, we demonstrate how a reversible shape-memory polymer actuation can be generated in a single micro/nano object, where the shape change during actuation of an individual fiber can be dictated by programming using an AFM-based method. Electrospinning was used to prepare poly(epsilon-caprolactone) micro-/nanofibers, which were fixed and crosslinked on a structured silicon wafer. The programming as well as the observation of recovery and reversible displacement of the fiber were performed by vertical three point bending, using an AFM testing platform introduced here. A plateau tip was utilized to improve the stability of the fiber contact and working distance, enabling larger deformations and greater rbSMPA performance. Values for the reversible elongation of epsilon(rev)= 3.4 +/- 0.1\% and 10.5 +/- 0.1\% were obtained for a single micro (d = 1.0 +/- 0.2 mu m) and nanofiber (d = 300 +/- 100 nm) in cyclic testing between the temperatures 10 and 60 degrees C. The reversible actuation of the nanofiber was successfully characterized for 10 cycles. The demonstration and characterization of individual shape-memory nano and microfiber actuators represents an important step in the creation of miniaturized robotic devices capable of performing complex physical functions at the length scale of cells and structural component of the extracellular matrix.}, language = {en} } @article{NeffeIzraylitHommesSchattmannetal.2021, author = {Neffe, Axel T. and Izraylit, Victor and Hommes-Schattmann, Paul J. and Lendlein, Andreas}, title = {Soft, formstable (Co)polyester blend elastomers}, series = {Nanomaterials : open access journal}, volume = {11}, journal = {Nanomaterials : open access journal}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {2079-4991}, doi = {10.3390/nano11061472}, pages = {18}, year = {2021}, abstract = {High crystallization rate and thermomechanical stability make polylactide stereocomplexes effective nanosized physical netpoints. Here, we address the need for soft, form-stable degradable elastomers for medical applications by designing such blends from (co)polyesters, whose mechanical properties are ruled by their nanodimensional architecture and which are applied as single components in implants. By careful controlling of the copolymer composition and sequence structure of poly[(L-lactide)-co-(epsilon-caprolactone)], it is possible to prepare hyperelastic polymer blends formed through stereocomplexation by adding poly(D-lactide) (PDLA). Low glass transition temperature T-g <= 0 degrees C of the mixed amorphous phase contributes to the low Young's modulus E. The formation of stereocomplexes is shown in DSC by melting transitions T-m > 190 degrees C and in WAXS by distinct scattering maxima at 2 theta = 12 degrees and 21 degrees. Tensile testing demonstrated that the blends are soft (E = 12-80 MPa) and show an excellent hyperelastic recovery R-rec = 66-85\% while having high elongation at break epsilon(b) up to >1000\%. These properties of the blends are attained only when the copolymer has 56-62 wt\% lactide content, a weight average molar mass >140 kg center dot mol(-1), and number average lactide sequence length >= 4.8, while the blend is formed with a content of 5-10 wt\% of PDLA. The devised strategy to identify a suitable copolymer for stereocomplexation and blend formation is transferable to further polymer systems and will support the development of thermoplastic elastomers suitable for medical applications.}, language = {en} } @article{BaeckemoLiuLendlein2021, author = {B{\"a}ckemo, Johan Dag Valentin and Liu, Yue and Lendlein, Andreas}, title = {Bio-inspired and computer-supported design of modulated shape changes in polymer materials}, series = {MRS communications / a publication of the Materials Research Society}, volume = {11}, journal = {MRS communications / a publication of the Materials Research Society}, number = {4}, publisher = {Springer}, address = {Berlin}, issn = {2159-6867}, doi = {10.1557/s43579-021-00056-6}, pages = {462 -- 469}, year = {2021}, abstract = {The Venus flytrap is a fascinating plant with a finely tuned mechanical bi-stable system, which can switch between mono- and bi-stability. Here, we combine geometrical design of compliant mechanics and the function of shape-memory polymers to enable switching between bi- and mono-stable states. Digital design and modelling using the Chained Beam Constraint Model forecasted two geometries, which were experimentally realized as structured films of cross-linked poly[ethylene-co-(vinyl acetate)] supported by digital manufacturing. Mechanical evaluation confirmed our predicted features. We demonstrated that a shape-memory effect could switch between bi- and mono-stability for the same construct, effectively imitating the Venus flytrap.}, language = {en} } @article{FarhanBehlKratzetal.2021, author = {Farhan, Muhammad and Behl, Marc and Kratz, Karl and Lendlein, Andreas}, title = {Origami hand for soft robotics driven by thermally controlled polymeric fiber actuators}, series = {MRS communications / a publication of the Materials Research Society}, volume = {11}, journal = {MRS communications / a publication of the Materials Research Society}, number = {4}, publisher = {Springer}, address = {Berlin}, issn = {2159-6859}, doi = {10.1557/s43579-021-00058-4}, pages = {476 -- 482}, year = {2021}, abstract = {Active fibers can serve as artificial muscles in robotics or components of smart textiles. Here, we present an origami hand robot, where single fibers control the reversible movement of the fingers. A recovery/contracting force of 0.2 N with a work capacity of 0.175 kJ kg(-1) was observed in crosslinked poly[ethylene-co-(vinyl acetate)] (cPEVA) fibers, which could enable the bending movement of the fingers by contraction upon heating. The reversible opening of the fingers was attributed to a combination of elastic recovery force of the origami structure and crystallization-induced elongation of the fibers upon cooling.}, language = {en} } @article{LiuGouldRudolphetal.2020, author = {Liu, Yue and Gould, Oliver E. C. and Rudolph, Tobias and Fang, Liang and Kratz, Karl and Lendlein, Andreas}, title = {Polymeric microcuboids programmable for temperature-memory}, series = {Macromolecular materials and engineering}, volume = {305}, journal = {Macromolecular materials and engineering}, number = {10}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1438-7492}, doi = {10.1002/mame.202000333}, pages = {7}, year = {2020}, abstract = {Microobjects with programmable mechanical functionality are highly desirable for the creation of flexible electronics, sensors, and microfluidic systems, where fabrication/programming and quantification methods are required to fully control and implement dynamic physical behavior. Here, programmable microcuboids with defined geometries are prepared by a template-based method from crosslinked poly[ethylene-co-(vinyl acetate)] elastomers. These microobjects could be programmed to exhibit a temperature-memory effect or a shape-memory polymer actuation capability. Switching temperaturesT(sw)during shape recovery of 55 +/- 2, 68 +/- 2, 80 +/- 2, and 86 +/- 2 degrees C are achieved by tuning programming temperatures to 55, 70, 85, and 100 degrees C, respectively. Actuation is achieved with a reversible strain of 2.9 +/- 0.2\% to 6.7 +/- 0.1\%, whereby greater compression ratios and higher separation temperatures induce a more pronounced actuation. Micro-geometry change is quantified using optical microscopy and atomic force microscopy. The realization and quantification of microparticles, capable of a tunable temperature responsive shape-change or reversible actuation, represent a key development in the creation of soft microscale devices for drug delivery or microrobotics.}, language = {en} } @article{IzraylitLiuTarazonaetal.2021, author = {Izraylit, Victor and Liu, Yue and Tarazona, Natalia A. and Machatschek, Rainhard Gabriel and Lendlein, Andreas}, title = {Crystallization and degradation behaviour of multiblock copolyester blends in Langmuir monolayers}, series = {MRS communications / a publication of the Materials Research Society}, volume = {11}, journal = {MRS communications / a publication of the Materials Research Society}, number = {6}, publisher = {Springer}, address = {Berlin}, issn = {2159-6859}, doi = {10.1557/s43579-021-00107-y}, pages = {850 -- 855}, year = {2021}, abstract = {Supporting the wound healing of soft tissues requires fixation devices becoming more elastic while degrading. To address this unmet need, we designed a blend of degradable multiblock copolymers, which is cross-linked by PLA stereocomplexation combining two soft segments differing substantially in their hydrolytic degradation rate. The degradation path and concomitant structural changes are predicted by Langmuir monolayer technique. The fast hydrolysis of one soft segment leads to a decrease of the total polymer mass at constant physical cross-linking density. The corresponding increase of the average spacing between the network nodes suggests the targeted increase of the blend's flexibility.}, language = {en} } @article{IzraylitHeuchelKratzetal.2021, author = {Izraylit, Victor and Heuchel, Matthias and Kratz, Karl and Lendlein, Andreas}, title = {Non-woven shape-memory polymer blend actuators}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {6}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, number = {33}, publisher = {Springer Nature Switzerland AG}, address = {Cham}, issn = {2059-8521}, doi = {10.1557/s43580-021-00063-8}, pages = {781 -- 785}, year = {2021}, abstract = {The hierarchical design approach provides various opportunities to adjust the structural performance of polymer materials. Electrospinning processing techniques give access to molecular orientation as a design parameter, which we consider here in view of the shape-memory actuation performance. The aim of this work is to investigate how the reversible strain epsilon'(rev) can be affected by a morphology change from a bulk material to an electrospun mesh. epsilon'(rev) could be increased from 5.5 +/- 0.5\% to 15 +/- 1.8\% for a blend from a multiblock copolymer with poly(epsilon-caprolactone) (PCL) and poly(L-lactide) (PLLA) segments with oligo(D-lactide) (ODLA). This study demonstrates an effective design approach for enhancing soft actuator performance, which can be broadly applied in soft robotics and medicine.}, language = {en} } @article{MazurekBudzyńskaBehlNeumannetal.2022, author = {Mazurek-Budzyńska, Magdalena and Behl, Marc and Neumann, Richard and Lendlein, Andreas}, title = {4D-actuators by 3D-printing combined with water-based curing}, series = {Materials today. Communications}, volume = {30}, journal = {Materials today. Communications}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2352-4928}, doi = {10.1016/j.mtcomm.2021.102966}, pages = {7}, year = {2022}, abstract = {The shape and the actuation capability of state of the art robotic devices typically relies on multimaterial systems from a combination of geometry determining materials and actuation components. Here, we present multifunctional 4D-actuators processable by 3D-printing, in which the actuator functionality is integrated into the shaped body. The materials are based on crosslinked poly(carbonate-urea-urethane) networks (PCUU), synthesized in an integrated process, applying reactive extrusion and subsequent water-based curing. Actuation capability could be added to the PCUU, prepared from aliphatic oligocarbonate diol, isophorone diisocyanate (IPDI) and water, in a thermomechanical programming process. When programmed with a strain of epsilon(prog) = 1400\% the PCUU networks exhibited actuation apparent by reversible elongation epsilon'(rev) of up to 22\%. In a gripper a reversible bending epsilon'(rev)((be)(nd)()) in the range of 37-60\% was achieved when the actuation temperature (T-high) was varied between 45 degrees C and 49 degrees C. The integration of actuation and shape formation could be impressively demonstrated in two PCUU-based reversible fastening systems, which were able to hold weights of up to 1.1 kg. In this way, the multifunctional materials are interesting candidate materials for robotic applications where a freedom in shape design and actuation is required as well as for sustainable fastening systems.}, language = {en} } @article{NeffeZhangHommesSchattmannetal.2021, author = {Neffe, Axel T. and Zhang, Quanchao and Hommes-Schattmann, Paul J. and Lendlein, Andreas}, title = {Ethylene oxide sterilization of electrospun poly(L-lactide)/poly(D-lactide) core/shell nanofibers}, series = {MRS advances}, volume = {6}, journal = {MRS advances}, number = {33}, publisher = {Springer}, address = {Cham}, issn = {2059-8521}, doi = {10.1557/s43580-021-00058-5}, pages = {786 -- 789}, year = {2021}, abstract = {The application of polymers in medicine requires sterilization while retaining material structure and properties. This demands detailed analysis, which we show exemplarily for the sterilization of PLLA/PDLA core-shell nanofibers with ethylene oxide (EtO). The electrospun patch was exposed to EtO gas (6 vol\% in CO2, 1.7 bar) for 3 h at 45 degrees C and 75\% rel. humidity, followed by degassing under pressure/vacuum cycles for 12 h. GC-MS analysis showed that no residual EtO was retained. Fiber diameters (similar to 520 +/- 130 nm) of the patches remained constant as observed by electron microscopy. Young's modulus slightly increased and the elongation at break slightly decreased, determined at 37 degrees C. No changes were detected in H-1-NMR spectra, in molar mass distribution (GPC) or in crystallinity measured for annealed samples with comparable thermal history (Wide Angle X-Ray Scattering). Altogether, EtO emerged as suitable sterilization method for polylactide nanofibers with core-shell morphology.}, language = {en} } @article{FarhanChaudharyNoecheletal.2020, author = {Farhan, Muhammad and Chaudhary, Deeptangshu and N{\"o}chel, Ulrich and Behl, Marc and Kratz, Karl and Lendlein, Andreas}, title = {Electrical actuation of coated and composite fibers based on poly[ethylene-co-(vinyl acetate)]}, series = {Macromolecular materials and engineering}, volume = {306}, journal = {Macromolecular materials and engineering}, number = {2}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1438-7492}, doi = {10.1002/mame.202000579}, pages = {8}, year = {2020}, abstract = {Robots are typically controlled by electrical signals. Resistive heating is an option to electrically trigger actuation in thermosensitive polymer systems. In this study electrically triggerable poly[ethylene-co-(vinyl acetate)] (PEVA)-based fiber actuators are realized as composite fibers as well as polymer fibers with conductive coatings. In the coated fibers, the core consists of crosslinked PEVA (cPEVA), while the conductive coating shell is achieved via a dip coating procedure with a coating thickness between 10 and 140 mu m. The conductivity of coated fibers sigma = 300-550 S m(-1) is much higher than that of the composite fibers sigma = 5.5 S m(-1). A voltage (U) of 110 V is required to heat 30 cm of coated fiber to a targeted temperature of approximate to 65 degrees C for switching in less than a minute. Cyclic electrical actuation investigations reveal epsilon '(rev) = 5 +/- 1\% reversible change in length for coated fibers. The fabrication of such electro-conductive polymeric actuators is suitable for upscaling so that their application potential as artificial muscles can be explored in future studies.}, language = {en} } @article{YouBehlLoewenbergetal.2017, author = {You, Zewang and Behl, Marc and L{\"o}wenberg, Candy and Lendlein, Andreas}, title = {pH-sensitivity and conformation change of the n-terminal methacrylated peptide VK20}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {2}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, publisher = {Cambridge University Press}, address = {Cambridge}, issn = {2059-8521}, doi = {10.1557/adv.2017.491}, pages = {2571 -- 2579}, year = {2017}, abstract = {N-terminal methacrylation of peptide MAXI, which is capable of conformational changes variation of the pH, results in a peptide, named VK20. Increasing the reactivity of this terminal group enables further coupling reactions or chemical modifications of the peptidc. However, this end group functionalization may influence the ability of confonnational changes of VK20; as well as its properties. In this paper; the influence of pH on the transition between random coil and beta-sheet conformation of VK20; including the transition kinetics, were investigated. At pH values of 9 and higher, the kinetics beta-sheet formation increased tor VK(2 0, compared to MAXI. The self-assembly into beta-sheets recognized by the formation of a physically crosslinked gel was furthermore indicated by a significant increase of G. An increase in pH (from 9 to 9.5) led to a faster gelation of the peptide VK20. Simultaneously, G was increased from 460 +/- 70 Pa (at pH 9) to 1520 +/- 180 Pa (at pH 9.5). At the nanoscale, the gel showed a highly interconnected fibrillar/network structure with uniform fibril widths of approximately 3.4 +/- 0.5 nm (N=30). The recovery of the peptide conformation back to random coil resulted in the dissolution of the gel; whereby the kinetics of the recovery depended on the pH. Conclusively, the ability of MAXI to undergo confommtional changes was not affected by N-terminal methacrylation whereas the kinetics of pH-sensitive beta-sheet formations has been increased.}, language = {en} } @article{PengBehlZhangetal.2017, author = {Peng, Xingzhou and Behl, Marc and Zhang, Pengfei and Mazurek-Budzyńska, Magdalena and Feng, Yakai and Lendlein, Andreas}, title = {Synthesis and characterization of multiblock poly(ester-amide-urethane)s}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {2}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, publisher = {Cambridge University Press}, address = {Cambridge}, issn = {2059-8521}, doi = {10.1557/adv.2017.486}, pages = {2551 -- 2559}, year = {2017}, abstract = {In this study, a multiblock copolymer containing oligo(3-methyl-morpholine-2, 5-dione) (oMMD) and oligo(3-sec-butyl-morpholine-2, 5-dione) (oBMD) building blocks obtained by ring-opening polymerization (ROP) of the corresponding monomers, was synthesized in a polyaddition reaction using an aliphatic diisocyanate. The multiblock copolymer (pBMD-MMD) provided a molecular weight of 40, 000 g·mol-1, determined by gel permeation chromatography (GPC). Incorporation of both oligodepsipeptide segments in multiblock copolymers was confirmed by 1H NMR and Matrix Assisted Laser Desorption/Ionization Time Of Flight Mass Spectroscopy (MALDI-TOF MS) analysis. pBMD-MMD showed two separated glass transition temperatures (61 °C and 74 °C) indicating a microphase separation. Furthermore, a broad glass transition was observed by DMTA, which can be attributed to strong physical interaction i.e. by H-bonds formed between amide, ester, and urethane groups of the investigated copolymers. The obtained multiblock copolymer is supposed to own the capability to exhibit strong physical interactions.}, language = {en} } @article{LiuRazzaqRudolphetal.2017, author = {Liu, Yue and Razzaq, Muhammad Yasar and Rudolph, Tobias and Fang, Liang and Kratz, Karl and Lendlein, Andreas}, title = {Two-Level Shape Changes of Polymeric Microcuboids Prepared from Crystallizable Copolymer Networks}, series = {Macromolecules : a publication of the American Chemical Society}, volume = {50}, journal = {Macromolecules : a publication of the American Chemical Society}, publisher = {American Chemical Society}, address = {Washington}, issn = {0024-9297}, doi = {10.1021/acs.macromol.6b02237}, pages = {2518 -- 2527}, year = {2017}, abstract = {Polymeric microdevices bearing features like nonspherical shapes or spatially segregated surface properties are of increasing importance in biological and medical analysis, drug delivery, and bioimaging or microfluidic systems as well as in micromechanics, sensors, information storage, or data carrier devices. Here, a method to fabricate programmable microcuboids with shape-memory capability and the quantification of their recovery at different levels is reported. The method uses the soft lithographic technique to create microcuboids with well-defined sizes and surface properties. Microcuboids having an edge length of 25 mu m and a height of 10 mu m were prepared from cross-linked poly[ethylene-co-(vinyl acetate)] (cPEVA) with different vinyl acetate contents and were programmed by compression with various deformation degrees at elevated temperatures. The microlevel shape-recovery of the cuboidal geometry during heating was monitored by optical microscopy (OM) and atomic force microscopy (AFM) studying the related changes in the projected area (PA) or height, while the nanolevel changes of the nanosurface roughness were investigated by in situ AFM. The shape-memory effect at the microlevel was quantified by the recovery ratio of cuboids (R-r,R-micro), while at the. nanolevel, the recovery ratio of the nanoroughness (R-r,R-nano) was measured. The values of R-r,R-micro,,micro could be tailored in a range from 42 +/- 1\% to 102 +/- 1\% and Rr,nano from 89 +/- 6\% to 136 +/- 21\% depending on the applied compression ratio and the amount of vinyl acetate content in the cPEVA microcuboids.}, language = {en} } @article{BrunacciWischkeNaolouetal.2017, author = {Brunacci, Nadia and Wischke, Christian and Naolou, Toufik and Neffe, Axel T. and Lendlein, Andreas}, title = {Influence of surfactants on depsipeptide submicron particle formation}, series = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {116}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2016.11.011}, pages = {61 -- 65}, year = {2017}, abstract = {Surfactants are required for the formation and stabilization of hydrophobic polymeric particles in aqueous environment. In order to form submicron particles of varying sizes from oligo[3-(S)-sec-butylmorpholine-2,5-dione]diols ((OBMD)-diol), different surfactants were investigated. As new surfactants, four-armed star-shaped oligo(ethylene glycol)s of molecular weights of 5-20 kDa functionalized with desamino-tyrosine (sOEG-DAT) resulted in smaller particles with lower PDI than with desaminotyrosyl tyrosine (sOEG-DATT) in an emulsion/solvent evaporation method. In a second set of experiments, sOEG-DAT of M-n= 10 kDa was compared with the commonly employed emulsifiers polyvinylalcohol (PVA), polyoxyethylene (20) sorbitan monolaurate (Tween 20), and D-alpha-tocopherol polyethylene glycol succinate (VIT E-TPGS) for OBMD particle preparation. sOEG-DAT allowed to systematically change sizes in a range of 300 up to 900 nm with narrow polydispersity, while in the other cases, a lower size range (250-400 nm, PVA; 300 nm, Tween 20) or no effective particle formation was observed. The ability of tailoring particle size in a broad range makes sOEG-DAT of particular interest for the formation of oligodepsipeptide particles, which can further be investigated as drug carriers for controlled delivery. (C) 2016 Elsevier B.V. All rights reserved.}, language = {en} } @misc{NaolouRuehlLendlein2017, author = {Naolou, Toufik and R{\"u}hl, Eckart and Lendlein, Andreas}, title = {Nanocarriers}, series = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {116}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2017.03.004}, pages = {1 -- 3}, year = {2017}, language = {en} } @article{KruegerGengeSchulzKratzetal.2018, author = {Kr{\"u}ger-Genge, Anne and Schulz, Christian and Kratz, Karl and Lendlein, Andreas and Jung, Friedrich}, title = {Comparison of two substrate materials used as negative control in endothelialization studies}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {69}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {3}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-189904}, pages = {437 -- 445}, year = {2018}, abstract = {The endothelialization of synthetic surfaces applied as cardiovascular implant materials is an important issue to ensure the anti-thrombotic quality of a biomaterial. However, the rapid and constant development of a functionallycon-fluent endothelial cell monolayer is challenging. In order to investigate the compatibility of potential implant materials with endothelial cells several in vitro studies are performed. Here, glass and tissue culture plates (TCP) are often used as reference materials for in vitro pre-testing. However, a direct comparison of both substrates is lacking. Therefore, a comparison of study results is difficult, since results are often related to various reference materials. In this study, the endothelialization of glass and TCP was investigated in terms of adherence, morphology, integrity, viability and function using human umbilical vein endothelial cells (HUVEC). On both substrates an almost functionally confluent HUVEC monolayer was developed after nine days of cell seeding with clearly visible cell rims, decreased stress fiber formation and a pronounced marginal filament band. The viability of HUVEC was comparable for both substrates nine days after cell seeding with only a few dead cells. According to that, the cell membrane integrity as well as the metabolic activity showed no differences between TCP and glass. However, a significant difference was observed for the secretion of IL-6 and IL-8. The concentration of both cytokines, which are associated with migratory activity, was increased in the supernatant of HUVEC seeded on TCP. This result matches well with the slightly increased number of adherent HUVEC on TCP. In conclusion, these findings indicate that both reference materials are almost comparable and can be used equivalently as control materials in in vitro endothelialization studies.}, language = {en} } @article{KruegerGengeBrauneWalteretal.2018, author = {Kr{\"u}ger-Genge, A. and Braune, S. and Walter, M. and Krengel, M. and Kratz, K. and K{\"u}pper, J. H. and Lendlein, Andreas and Jung, Friedrich}, title = {Influence of different surface treatments of poly(n-butyl acrylate) networks on fibroblasts adhesion, morphology and viability}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {69}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {1-2}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-189130}, pages = {305 -- 316}, year = {2018}, abstract = {BACKGROUND: Physical and chemical characteristics of implant materials determine the fate of long-term cardiovascular devices. However, there is still a lack of fundamental understanding of the molecular mechanisms occurring in the material-tissue interphase. In a previous study, soft covalently crosslinked poly(n-butyl acrylate) networks (cPnBA) were introduced as sterilizable, non-toxic and immuno-compatible biomaterials with mechanical properties adjustable to blood vessels. Here we study the influence of different surface treatments in particular oxygen plasma modification and fibrinogen deposition as well as a combinatorial approach on the adhesion and viability of fibroblasts. RESULTS: Compared to non-treated cPnBAs the advancing water-contact angles were found to be reduced after all surface modifications (p<0.05, each), while lowest values were observed after the combined surface treatment (OPT+FIB). The latter differed significantly from the single OPT and FIB. The number of adherent fibroblasts and their adherence behavior differed on both pristine cPnBA networks. The fibroblast density on cPnBA04 was 743 +/- 434 cells. mm(-2), was about 6.5 times higher than on cPnBA73 with 115 +/- 73 cells. mm(-2). On cPnBA04 about 20\% of the cells were visible as very small, round and buckled cells while all other cells were in a migrating status. On cPnBA73, nearly 50\% of fibroblasts were visible as very small, round and buckled cells. The surface functionalization either using oxygen plasma treatment or fibrinogen coating led to a significant increase of adherent fibroblasts, particularly the combination of both techniques, for both cPnBA networks. It is noteworthy to mention that the fibrinogen coating overruled the characteristics of the pristine surfaces; here, the fibroblast densities after seeding were identical for both cPnBAnetworks. Thus, the binding rather depended on the fibrinogen coating than on the substrate characteristics anymore. While the integrity of the fibroblasts membrane was comparable for both polymers, the MTS tests showed a decreased metabolic activity of the fibroblasts on cPnBA. CONCLUSION: The applied surface treatments of cPnBA successfully improved the adhesion of viable fibroblasts. Under resting conditions as well as after shearing the highest fibroblast densities were found on surfaces with combined post-treatment.}, language = {en} } @article{KumarHeuchelKratzetal.2018, author = {Kumar, Reddi K. and Heuchel, Matthias and Kratz, Karl and Lendlein, Andreas and Jankowski, Joachim and Tetali, Sarada D.}, title = {Effects of extracts prepared from modified porous poly(ether imide) microparticulate absorbers on cytotoxicity, macrophage differentiation and proinflammatory behavior of human monocytic (THP-1) cells}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {69}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {1-2}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-189112}, pages = {175 -- 185}, year = {2018}, abstract = {Remaining uremic toxins in the blood of chronic renal failure patients represent one central challenge in hemodialysis therapies. Highly porous poly(ether imide) (PEI) microparticles have been recently introduced as candidate absorber materials, which show a high absorption capacity for uremic toxins and allow hydrophilic surface modification suitable for minimization of serum protein absorption. In this work, the effects of extracts prepared from PEI microparticles modified by nucleophilic reaction with low molecular weight polyethylene imine (Pei) or potassium hydroxide (KOH), on human monocytic (THP-1) cells are studied. The obtained results suggested that the extracts of Pei and KOH modified PEI absorbers have no negative effect on THP-1 cell viability and do not initiate the critical differentiation towards macrophages. The extracts did not enhance transcript or protein levels of investigated proinflammatory markers in THP-1 cells, namely, TNF alpha, MCP1, IL6 and IL8. Based on these findings such modified PEI microparticles should be qualified for further pre-clinical evaluation i.e. in an in vivo animal experiment.}, language = {en} } @article{NieWangXuetal.2019, author = {Nie, Yan and Wang, Weiwei and Xu, Xun and Zou, Jie and Bhuvanesh, Thanga and Schulz, Burkhard and Ma, Nan and Lendlein, Andreas}, title = {Enhancement of human induced pluripotent stem cells adhesion through multilayer laminin coating}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {70}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {4}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-189318}, pages = {531 -- 542}, year = {2019}, abstract = {Bioengineered cell substrates are a highly promising tool to govern the differentiation of stem cells in vitro and to modulate the cellular behavior in vivo. While this technology works fine for adult stem cells, the cultivation of human induced pluripotent stem cells (hiPSCs) is challenging as these cells typically show poor attachment on the bioengineered substrates, which among other effects causes substantial cell death. Thus, very limited types of surfaces have been demonstrated suitable for hiPSC cultures. The multilayer coating approach that renders the surface with diverse chemical compositions, architectures, and functions can be used to improve the adhesion of hiPSCs on the bioengineered substrates. We hypothesized that a multilayer formation based on the attraction of molecules with opposite charges could functionalize the polystyrene (PS) substrates to improve the adhesion of hiPSCs. Polymeric substrates were stepwise coated, first with dopamine to form a polydopamine (PDA) layer, second with polylysine and last with Laminin-521. The multilayer formation resulted in the variation of hydrophilicity and chemical functionality of the surfaces. Hydrophilicity was detected using captive bubble method and the amount of primary and secondary amines on the surface was quantified by fluorescent staining. The PDA layer effectively immobilized the upper layers and thereby improved the attachment of hiPSCs. Cell adhesion was enhanced on the surfaces coated with multilayers, as compared to those without PDA and/or polylysine. Moreover, hiPSCs spread well over this multilayer laminin substrate. These cells maintained their proliferation capacity and differentiation potential. The multilayer coating strategy is a promising attempt for engineering polymer-based substrates for the cultivation of hiPSCs and of interest for expanding the application scope of hiPSCs.}, language = {en} } @article{RazzaqBehlLendlein2018, author = {Razzaq, Muhammad Yasar and Behl, Marc and Lendlein, Andreas}, title = {Thermally-induced actuation of magnetic nanocomposites based on Oligo(ω-pentadecalactone) and covalently integrated magnetic nanoparticles}, series = {MRS advances: a journal of the Materials Research Society (MRS)}, volume = {3}, journal = {MRS advances: a journal of the Materials Research Society (MRS)}, number = {63}, publisher = {Cambridge University Press}, address = {New York}, issn = {2059-8521}, doi = {10.1557/adv.2018.613}, pages = {3783 -- 3791}, year = {2018}, abstract = {The incorporation of inorganic particles in a polymer matrix has been established as a method to adjust the mechanical performance of composite materials. We report on the influence of covalent integration of magnetic nanoparticles (MNP) on the actuation behavior and mechanical performance of hybrid nanocomposite (H-NC) based shape-memory polymer actuators (SMPA). The H-NC were synthesized by reacting two types of oligo(ω-pentadecalactone) (OPDL) based precursors with terminal hydroxy groups, a three arm OPDL (3 AOPDL, Mn = 6000 g mol•1-1 ) and an OPDL (Mn =3300 g • mol-1 ) coated magnetite nanoparticle ({\O} = 10 ± 2 nm), with a diisocyanate. These H-NC were compared to the homopolymer network regarding the actuation performance, contractual stress (σcontr) as well as thermal and mechanical properties. The melting range of the OPDL crystals (ΔTm,OPDL) was shifted in homo polymer networks from 36 ºC - 76 ºC to 41ºC - 81 °C for H-NC with 9 wt\% of MNP content. The actuators were explored by variation of separating temperature (Tsep), which splits the OPDL crystalline domain into actuating and geometry determining segments. Tsep was varied in the melting range of the nanocomposites and the actuation capability and contractual stress (σcontr) of the nanocomposite actuators could be adjusted. The reversible strain (εrev) was decreased from 11 ± 0.3\% for homo polymer network to 3.2±0.3\% for H-NC9 with 9 wt\% of MNP indicating a restraining effect of the MNP on chain mobility. The results show that the performance of H-NCs in terms of thermal and elastic properties can be tailored by MNP content, however for higher reversible actuation, lower MNP contents are preferable.}, language = {en} } @article{FarhanRudolphNoecheletal.2018, author = {Farhan, Muhammad and Rudolph, Tobias and N{\"o}chel, Ulrich and Kratz, Karl and Lendlein, Andreas}, title = {Extractable Free Polymer Chains Enhance Actuation Performance of Crystallizable Poly(epsilon-caprolactone) Networks and Enable Self-Healing}, series = {Polymers}, volume = {10}, journal = {Polymers}, number = {3}, publisher = {MDPI}, address = {Basel}, issn = {2073-4360}, doi = {10.3390/polym10030255}, pages = {15}, year = {2018}, abstract = {Crosslinking of thermoplastics is a versatile method to create crystallizable polymer networks, which are of high interest for shape-memory actuators. Here, crosslinked poly(epsilon-caprolactone) thermosets (cPCLs) were prepared from linear starting material, whereby the amount of extractable polymer was varied. Fractions of 5-60 wt \% of non-crosslinked polymer chains, which freely interpenetrate the crosslinked network, were achieved leading to differences in the resulting phase of the bulk material. This can be described as "sponge-like" with open or closed compartments depending on the amount of interpenetrating polymer. The crosslinking density and the average network chain length remained in a similar range for all network structures, while the theoretical accessible volume for reptation of the free polymer content is affected. This feature could influence or introduce new functions into the material created by thermomechanical treatment. The effect of interpenetrating PCL in cPCLs on the reversible actuation was analyzed by cyclic, uniaxial tensile tests. Here, high reversible strains of up to Delta epsilon = 24\% showed the enhanced actuation performance of networks with a non-crosslinked PCL content of 30 wt \% resulting from the crystal formation in the phase of the non-crosslinked PCL and co-crystallization with network structures. Additional functionalities are reprogrammability and self-healing capabilities for networks with high contents of extractable polymer enabling reusability and providing durable actuator materials.}, language = {en} } @article{PilusoVukicevieNoecheletal.2018, author = {Piluso, Susanna and Vukicevie, Radovan and N{\"o}chel, Ulrich and Braune, Steffen and Lendlein, Andreas and Neffe, Axel T.}, title = {Sequential alkyne-azide cycloadditions for functionalized gelatin hydrogel formation}, series = {European polymer journal}, volume = {100}, journal = {European polymer journal}, publisher = {Elsevier}, address = {Oxford}, issn = {0014-3057}, doi = {10.1016/j.eurpolymj.2018.01.017}, pages = {77 -- 85}, year = {2018}, abstract = {While click chemistry reactions for biopolymer network formation are attractive as the defined reactions may allow good control of the network formation and enable subsequent functionalization, tailoring of gelatin network properties over a wide range of mechanical properties has yet to be shown. Here, it is demonstrated that copper-catalyzed alkyne-azide cycloaddition of alkyne functionalized gelatin with diazides gave hydrogel networks with properties tailorable by the ratio of diazide to gelatin and diazide rigidity. 4,4′-diazido-2,2′-stilbenedisulfonic acid, which has been used as rigid crosslinker, yielded hydrogels with Young's moduli E of 50-390 kPa and swelling degrees Q of 150-250 vol.\%, while the more flexible 1,8-diazidooctane resulted in hydrogels with E = 125-280 kPa and Q = 225-470 vol.\%. Storage moduli could be varied by two orders of magnitude (G′ = 100-20,000 Pa). An indirect cytotoxicity test did not show cytotoxic properties. Even when employing 1:1 ratios of alkyne and azide moieties, the hydrogels were shown to contain both, unreacted alkyne groups on the gelatin backbone as well as dangling chains carrying azide groups as shown by reaction with functionalized fluorescein. The free groups, which can be tailored by the employed ratio of the reactants, are accessible for covalent attachment of drugs, as was demonstrated by functionalization with dexamethasone. The sequential network formation and functionalization with click chemistry allows access to multifunctional materials relevant for medical applications.}, language = {en} } @article{SaremAryaHeizmannetal.2018, author = {Sarem, Melika and Arya, Neha and Heizmann, Miriam and Neffe, Axel T. and Barbero, Andrea and Gebauer, Tim P. and Martin, Ivan and Lendlein, Andreas and Shastri, V. Prasad}, title = {Interplay between stiffness and degradation of architectured gelatin hydrogels leads to differential modulation of chondrogenesis in vitro and in vivo}, series = {Acta biomaterialia}, volume = {69}, journal = {Acta biomaterialia}, publisher = {Elsevier}, address = {Oxford}, issn = {1742-7061}, doi = {10.1016/j.actbio.2018.01.025}, pages = {83 -- 94}, year = {2018}, abstract = {The limited capacity of cartilage to heal large lesions through endogenous mechanisms has led to extensive effort to develop materials to facilitate chondrogenesis. Although physical-chemical properties of biomaterials have been shown to impact in vitro chondrogenesis, whether these findings are translatable in vivo is subject of debate. Herein, architectured 3D hydrogel scaffolds (ArcGel) (produced by crosslinking gelatin with ethyl lysine diisocyanate (LDI)) were used as a model system to investigate the interplay between scaffold mechanical properties and degradation on matrix deposition by human articular chondrocytes (HAC) from healthy donors in vitro and in vivo. Using ArcGel scaffolds of different tensile and shear modulus, and degradation behavior; in this study, we compared the fate of ex vivo engineeredArcGels-chondrocytes constructs, i.e. the traditional tissue engineering approach, with the de novo formation of cartilaginous tissue in HAC laden ArcGels in an ectopic nude mouse model. While the softer and fast degrading ArcGel (LNCO3) was more efficient at promoting chondrogenic differentiation in vitro, upon ectopic implantation, the stiffer and slow degrading ArcGel (LNCO8) was superior in maintaining chondrogenic phenotype in HAC and retention of cartilaginous matrix. Furthermore, surprisingly the de novo formation of cartilage tissue was promoted only in LNCO8. Since HAC cultured for only three days in the LNCO8 environment showed upregulation of hypoxia-associated genes, this suggests a potential role for hypoxia in the observed in vivo outcomes. In summary, this study sheds light on how immediate environment (in vivo versus in vitro) can significantly impact the outcomes of cell-laden biomaterials. Statement of Significance In this study, 3D architectured hydrogels (ArcGels) with different mechanical and biodegradation properties were investigated for their potential to promote formation of cartilaginous matrix by human articular chondrocytes in vitro and in vivo. Two paradigms were explored (i) ex vivo engineering followed by in vivo implantation in ectopic site of nude mice and (ii) short in vitro culture (3 days) followed by implantation to induce de novo cartilage formation. Softer and fast degrading ArcGel were better at promoting chondrogenesis in vitro, while stiffer and slow degrading ArcGel were strikingly superior in both maintaining chondrogenesis in vivo and inducing de novo formation of cartilage. Our findings highlight the importance of the interplay between scaffold mechanics and degradation in chondrogenesis.}, language = {en} } @misc{Lendlein2018, author = {Lendlein, Andreas}, title = {Fabrication of reprogrammable shape-memory polymer actuators for robotics}, series = {Science robotics}, volume = {3}, journal = {Science robotics}, number = {18}, publisher = {American Assoc. for the Advancement of Science}, address = {Washington}, issn = {2470-9476}, doi = {10.1126/scirobotics.aat9090}, pages = {2}, year = {2018}, abstract = {Shape-memory polymer actuators, whose actuation geometry and switching temperatures are reprogrammable by physical fabrication schemes, were recently suggested for robotics with the option for self-healing and degradability.}, language = {en} } @article{YanRudolphNoecheletal.2018, author = {Yan, Wan and Rudolph, Tobias and N{\"o}chel, Ulrich and Gould, Oliver E. C. and Behl, Marc and Kratz, Karl and Lendlein, Andreas}, title = {Reversible actuation of thermoplastic multiblock copolymers with overlapping thermal transitions of crystalline and glassy domains}, series = {Macromolecules : a publication of the American Chemical Society}, volume = {51}, journal = {Macromolecules : a publication of the American Chemical Society}, number = {12}, publisher = {American Chemical Society}, address = {Washington}, issn = {0024-9297}, doi = {10.1021/acs.macromol.8b00322}, pages = {4624 -- 4632}, year = {2018}, abstract = {Polymeric materials possessing specific features like programmability, high deformability, and easy processability are highly desirable for creating modern actuating systems. In this study, thermoplastic shape-memory polymer actuators obtained by combining crystallizable poly(epsilon-caprolactone) (PCL) and poly(3S-isobutylmorpholin-2,5-dione) (PIBMD) segments in multiblock copolymers are described. We designed these materials according to our hypothesis that the confinement of glassy PIBMD domains present at the upper actuation temperature contribute to the stability of the actuator skeleton, especially at large programming strains. The copolymers have a phase-segregated morphology, indicated by the well-separated melting and glass transition temperatures for PIBMD and PCL, but possess a partially overlapping T-m of PCL and T-g of PIBMD in the temperature interval from 40 to 60 degrees C. Crystalline PIBMD hard domains act as strong physical netpoints in the PIBMD-PCL bulk material enabling high deformability (up to 2000\%) and good elastic recoverability (up to 80\% at 50 degrees C above T-m,T-PCL). In the programmed thermoplastic actuators a high content of crystallizable PCL actuation domains ensures pronounced thermoreversible shape changes upon repetitive cooling and heating. The programmed actuator skeleton, composed of PCL crystals present at the upper actuation temperature T-high and the remaining glassy PIBMD domains, enabled oriented crystallization upon cooling. The actuation performance of PIBMD-PCL could be tailored by balancing the interplay between actuation and skeleton, but also by varying the quantity of crystalline PIBMD hard domains via the copolymer composition, the applied programming strain, and the choice of T-high. The actuator with 17 mol\% PIBMD showed the highest reversible elongation of 11.4\% when programmed to a strain of 900\% at 50 degrees C. It is anticipated that the presented thermoplastic actuator materials can be applied as modern compression textiles.}, language = {en} } @article{FangGouldLysyakovaetal.2018, author = {Fang, Liang and Gould, Oliver E. C. and Lysyakova, Liudmila and Jiang, Yi and Sauter, Tilman and Frank, Oliver and Becker, Tino and Schossig, Michael and Kratz, Karl and Lendlein, Andreas}, title = {Implementing and quantifying the shape-memory effect of single polymeric micro/nanowires with an atomic force microscope}, series = {ChemPhysChem : a European journal of chemical physics and physical chemistry}, volume = {19}, journal = {ChemPhysChem : a European journal of chemical physics and physical chemistry}, number = {16}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1439-4235}, doi = {10.1002/cphc.201701362}, pages = {2078 -- 2084}, year = {2018}, abstract = {The implementation of shape-memory effects (SME) in polymeric micro- or nano-objects currently relies on the application of indirect macroscopic manipulation techniques, for example, stretchable molds or phantoms, to ensembles of small objects. Here, we introduce a method capable of the controlled manipulation and SME quantification of individual micro- and nano-objects in analogy to macroscopic thermomechanical test procedures. An atomic force microscope was utilized to address individual electro-spun poly(ether urethane) (PEU) micro- or nanowires freely suspended between two micropillars on a micro-structured silicon substrate. In this way, programming strains of 10 +/- 1\% or 21 +/- 1\% were realized, which could be successfully fixed. An almost complete restoration of the original free-suspended shape during heating confirmed the excellent shape-memory performance of the PEU wires. Apparent recovery stresses of sigma(max,app)=1.2 +/- 0.1 and 33.3 +/- 0.1MPa were obtained for a single microwire and nanowire, respectively. The universal AFM test platform described here enables the implementation and quantification of a thermomechanically induced function for individual polymeric micro- and nanosystems.}, language = {en} } @article{TuncaboyluFriessWischkeetal.2018, author = {Tuncaboylu, Deniz Ceylan and Friess, Fabian and Wischke, Christian and Lendlein, Andreas}, title = {A multifunctional multimaterial system for on-demand protein release}, series = {Journal of controlled release}, volume = {284}, journal = {Journal of controlled release}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0168-3659}, doi = {10.1016/j.jconrel.2018.06.022}, pages = {240 -- 247}, year = {2018}, abstract = {In order to provide best control of the regeneration process for each individual patient, the release of protein drugs administered during surgery may need to be timely adapted and/or delayed according to the progress of healing/regeneration. This study aims to establish a multifunctional implant system for a local on-demand release, which is applicable for various types of proteins. It was hypothesized that a tubular multimaterial container kit, which hosts the protein of interest as a solution or gel formulation, would enable on-demand release if equipped with the capacity of diameter reduction upon external stimulation. Using devices from poly(epsilon-caprolactone) networks, it could be demonstrated that a shape-memory effect activated by heat or NIR light enabled on-demand tube shrinkage. The decrease of diameter of these shape-memory tubes (SMT) allowed expelling the payload as demonstrated for several proteins including SDF-1 alpha, a therapeutically relevant chemotactic protein, to achieve e.g. continuous release with a triggered add-on dosing (open tube) or an on-demand onset of bolus or sustained release (sealed tube). Considering the clinical relevance of protein factors in (stem) cell attraction to lesions and the progress in monitoring biomarkers in body fluids, such on-demand release systems may be further explored e.g. in heart, nerve, or bone regeneration in the future.}, language = {en} } @article{WangRazzaqRudolphetal.2018, author = {Wang, Li and Razzaq, Muhammad Yasar and Rudolph, Tobias and Heuchel, Matthias and N{\"o}chel, Ulrich and Mansfeld, Ulrich and Jiang, Yi and Gould, Oliver E. C. and Behl, Marc and Kratz, Karl and Lendlein, Andreas}, title = {Reprogrammable, magnetically controlled polymeric nanocomposite actuators}, series = {Material horizons}, volume = {5}, journal = {Material horizons}, number = {5}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {2051-6347}, doi = {10.1039/c8mh00266e}, pages = {861 -- 867}, year = {2018}, abstract = {Soft robots and devices with the advanced capability to perform adaptive motions similar to that of human beings often have stimuli-sensitive polymeric materials as the key actuating component. The external signals triggering the smart polymers' actuations can be transmitted either via a direct physical connection between actuator and controlling unit (tethered) or remotely without a connecting wire. However, the vast majority of such polymeric actuator materials are limited to one specific type of motion as their geometrical information is chemically fixed. Here, we present magnetically driven nanocomposite actuators, which can be reversibly reprogrammed to different actuation geometries by a solely physical procedure. Our approach is based on nanocomposite materials comprising spatially segregated crystallizable actuation and geometry determining units. Upon exposure to a specific magnetic field strength the actuators' geometric memory is erased by the melting of the geometry determining units allowing the implementation of a new actuator shape. The actuation performance of the nanocomposites can be tuned and the technical significance was demonstrated in a multi-cyclic experiment with several hundreds of repetitive free-standing shape shifts without losing performance.}, language = {en} } @article{PengBehlZhangetal.2018, author = {Peng, Xingzhou and Behl, Marc and Zhang, Pengfei and Mazurek-Budzynska, Magdalena and Feng, Yakai and Lendlein, Andreas}, title = {Synthesis of Well-Defined Dihydroxy Telechelics by (Co)polymerization of Morpholine-2,5-Diones Catalyzed by Sn(IV) Alkoxide}, series = {Macromolecular bioscience}, volume = {18}, journal = {Macromolecular bioscience}, number = {12}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1616-5187}, doi = {10.1002/mabi.201800257}, pages = {11}, year = {2018}, abstract = {Well-defined dihydroxy telechelic oligodepsipeptides (oDPs), which have a high application potential as building blocks for scaffold materials for tissue engineering applications or particulate carrier systems for drug delivery applications are synthesized by ring-opening polymerization (ROP) of morpholine-2,5-diones (MDs) catalyzed by 1,1,6,6-tetra-n-butyl-1,6-distanna-2,5,7,10-tetraoxacyclodecane (Sn(IV) alkoxide). In contrast to ROP catalyzed by Sn(Oct)(2), the usage of Sn(IV) alkoxide leads to oDPs, with less side products and well-defined end groups, which is crucial for potential pharmaceutical applications. A slightly faster reaction of the ROP catalyzed by Sn(IV) alkoxide compared to the ROP initiated by Sn(Oct)(2)/EG is found. Copolymerization of different MDs resulted in amorphous copolymers with T(g)s between 44 and 54 degrees C depending on the molar comonomer ratios in the range from 25\% to 75\%. Based on the well-defined telechelic character of the Sn(IV) alkoxide synthesized oDPs as determined by matrix-assisted laser desorption/ionization time of flight measurements, they resemble interesting building blocks for subsequent postfunctionalization or multifunctional materials based on multiblock copolymer systems whereas the amorphous oDP-based copolymers are interesting building blocks for matrices of drug delivery systems.}, language = {en} } @article{SaretiaMachatschekSchulzetal.2019, author = {Saretia, Shivam and Machatschek, Rainhard Gabriel and Schulz, Burkhard and Lendlein, Andreas}, title = {Reversible 2D networks of oligo(epsilon-caprolactone) at the air-water interface}, series = {Biomedical Materials}, volume = {14}, journal = {Biomedical Materials}, number = {3}, publisher = {IOP Publ. Ltd.}, address = {Bristol}, issn = {1748-6041}, doi = {10.1088/1748-605X/ab0cef}, pages = {10}, year = {2019}, abstract = {Hydroxyl terminated oligo(epsilon-caprolactone) (OCL) monolayers were reversibly cross-linked forming two dimensional networks (2D) at the air-water interface. The equilibrium reaction with glyoxal as the cross-linker is pH-sensitive. Pronounced contraction in the area of the prepared 2DOCL films in dependence of surface pressure and time revealed the process of the reaction. Cross-linking inhibited crystallization and retarded enzymatic degradation of the OCLfilm. Altering the subphase pH led to a cleavage of the covalent acetal cross-links. The reversibility of the covalent acetal cross-links was proved by observing an identical isotherm as non-cross-linked sample. Besides as model systems, these customizable reversible OCL2D networks are intended for use as pHresponsive drug delivery systems or functionalized cell culture substrates.}, language = {en} } @article{HauserWodtkeTonderaetal.2019, author = {Hauser, Sandra and Wodtke, Robert and Tondera, Christoph and Wodtke, Johanna and Neffe, Axel T. and Hampe, Jochen and Lendlein, Andreas and L{\"o}ser, Reik and Pietzsch, Jens}, title = {Characterization of Tissue Transglutaminase as a Potential Biomarker for Tissue Response toward Biomaterials}, series = {ACS biomaterials science \& engineering}, volume = {5}, journal = {ACS biomaterials science \& engineering}, number = {11}, publisher = {American Chemical Society}, address = {Washington}, issn = {2373-9878}, doi = {10.1021/acsbiomaterials.9b01299}, pages = {5979 -- 5989}, year = {2019}, abstract = {Tissue transglutaminase (TGase 2) is proposed to be important for biomaterial-tissue interactions due to its presence and versatile functions in the extracellular environment. TGase 2 catalyzes the cross-linking of proteins through its Ca2+-dependent acyltransferase activity. Moreover, it enhances the interactions between fibronectin and integrins, which in turn mediates the adhesion, migration, and motility of the cells. TGase 2 is also a key player in the pathogenesis of fibrosis. In this study, we investigated whether TGase 2 is present at the biomaterial tissue interface and might serve as an informative biomarker for the visualization of tissue response toward gelatin-based biomaterials. Two differently cross-linked hydrogels were used, which were obtained by the reaction of gelatin with lysine diisocyanate ethyl ester. The overall expression of TGase 2 by endothelial cells, macrophages, and granulocytes was partly influenced by contact to the hydrogels or their degradation products, although no clear correlation was evidenced. In contrast, the secretion of TGase 2 differed remarkably between the different cells, indicating that it might be involved in the cellular reaction toward gelatin-based hydrogels. The hydrogels were implanted subcutaneously in immunocompetent, hairless SKH1-Elite mice. Ex vivo immunohistochemical analysis of tissue sections over 112 days revealed enhanced expression of TGase 2 around the hydrogels, in particular at days 14 and 21 post-implantation. The incorporation of fluorescently labeled cadaverine derivatives for the detection of active TGase 2 was in accordance with the results of the expression analysis. The presence of an irreversible inhibitor of TGase 2 led to attenuated incorporation of the cadaverines, which verified the catalytic action of TGase 2. Our in vitro and ex vivo results verified TGase 2 as a potential biomarker for tissue response toward gelatin-based hydrogels. In vivo, no TGase 2 activity was detectable, which is mainly attributed to the unfavorable physicochemical properties of the cadaverine probe used.}, language = {en} } @article{RazzaqBehlHeucheletal.2019, author = {Razzaq, Muhammad Yasar and Behl, Marc and Heuchel, Matthias and Lendlein, Andreas}, title = {Matching magnetic heating and thermal actuation for sequential coupling in hybrid composites by design}, series = {Macromolecular rapid communications}, volume = {41}, journal = {Macromolecular rapid communications}, number = {1}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1022-1336}, doi = {10.1002/marc.201900440}, pages = {7}, year = {2019}, abstract = {Sequentially coupling two material functions requires matching the output from the first with the input of the second function. Here, magnetic heating controls thermal actuation of a hybrid composite in a challenging system environment causing an elevated level of heat loss. The concept is a hierarchical design consisting of an inner actuator of nanocomposite material, which can be remotely heated by exposure to an alternating magnetic field (AMF) and outer layers of a porous composite system with a closed pore morphology. These porous layers act as heat insulators and as barriers to the surrounding water. By exposure to the AMF, a local bulk temperature of 71 degrees C enables the magnetic actuation of the device, while the temperature of the surrounding water is kept below 50 degrees C. Interestingly, the heat loss during magnetic heating leads to an increase of the water phase (small volume) temperature. The temperature increase is able to sequentially trigger an adjacent thermal actuator attached to the actuator composite. In this way it could be demonstrated how the AMF is able to initiate two kinds of independent actuations, which might be interesting for robotics operating in aqueous environments.}, language = {en} } @article{ReinthalerJohanssonBrauneetal.2019, author = {Reinthaler, Markus and Johansson, Johan Backemo and Braune, Steffen and Al-Hindwan, Haitham Saleh Ali and Lendlein, Andreas and Jung, Friedrich}, title = {Shear-induced platelet adherence and activation in an in-vitro dynamic multiwell-plate system}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {71}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {2}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-189410}, pages = {183 -- 191}, year = {2019}, abstract = {Circulating blood cells are prone to varying flow conditions when contacting cardiovascular devices. For a profound understanding of the complex interplay between the blood components/cells and cardiovascular implant surfaces, testing under varying shear conditions is required. Here, we study the influence of arterial and venous shear conditions on the in vitro evaluation of the thrombogenicity of polymer-based implant materials. Medical grade poly(dimethyl siloxane) (PDMS), polyethylene terephthalate (PET) and polytetrafluoroethylene (PTFE) films were included as reference materials. The polymers were exposed to whole blood from healthy humans. Blood was agitated orbitally at low (venous shear stress: 2.8 dyne. cm(-2)) and high (arterial shear stress: 22.2 dyne .cm(-2)) agitation speeds in a well-plate based test system. Numbers of non-adherent platelets, platelet activation (P-Selectin positive platelets), platelet function (PFA100 closure times) and platelet adhesion (laser scanning microscopy (LSM)) were determined. Microscopic data and counting of the circulating cells revealed increasing numbers of material-surface adherent platelets with increasing agitation speed. Also, activation of the platelets was substantially increased when tested under the high shear conditions (P-Selectin levels, PFA-100 closure times). At low agitation speed, the platelet densities did not differ between the three materials. Tested at the high agitation speed, lowest platelet densities were observed on PDMS, intermediate levels on PET and highest on PTFE. While activation of the circulating platelets was affected by the implant surfaces in a similar manner, PFA closure times did not reflect this trend. Differences in the thrombogenicity of the studied polymers were more pronounced when tested at high agitation speed due to the induced shear stresses. Testing under varying shear stresses, thus, led to a different evaluation of the implant thrombogenicity, which emphasizes the need for testing under various flow conditions. Our data further confirmed earlier findings where the same reference implants were tested under static (and not dynamic) conditions and with fresh human platelet rich plasma instead of whole blood. This supports that the application of common reference materials may improve inter-study comparisons, even under varying test conditions.}, language = {en} } @article{WangXuLietal.2019, author = {Wang, Weiwei and Xu, Xun and Li, Zhengdong and Kratz, Karl and Ma, Nan and Lendlein, Andreas}, title = {Modulating human mesenchymal stem cells using poly(n-butyl acrylate) networks in vitro with elasticity matching human arteries}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {71}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {2}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-189418}, pages = {277 -- 289}, year = {2019}, abstract = {Non-swelling hydrophobic poly(n-butyl acrylate) network (cPnBA) is a candidate material for synthetic vascular grafts owing to its low toxicity and tailorable mechanical properties. Mesenchymal stem cells (MSCs) are an attractive cell type for accelerating endothelialization because of their superior anti-thrombosis and immune modulatory function. Further, they can differentiate into smooth muscle cells or endothelial-like cells and secret pro-angiogenic factors such as vascular endothelial growth factor (VEGF). MSCs are sensitive to the substrate mechanical properties, with the alteration of their major cellular behavior and functions as a response to substrate elasticity. Here, we cultured human adipose-derived mesenchymal stem cells (hADSCs) on cPnBAs with different mechanical properties (cPnBA250, Young's modulus (E) = 250 kPa; cPnBA1100, E = 1100 kPa) matching the elasticity of native arteries, and investigated their cellular response to the materials including cell attachment, proliferation, viability, apoptosis, senescence and secretion. The cPnBA allowed high cell attachment and showed negligible cytotoxicity. F-actin assembly of hADSCs decreased on cPnBA films compared to classical tissue culture plate. The difference of cPnBA elasticity did not show dramatic effects on cell attachment, morphology, cytoskeleton assembly, apoptosis and senescence. Cells on cPnBA250, with lower proliferation rate, had significantly higher VEGF secretion activity. These results demonstrated that tuning polymer elasticity to regulate human stem cells might be a potential strategy for constructing stem cell-based artificial blood vessels.}, language = {en} } @article{RazzaqBehlLendlein2019, author = {Razzaq, Muhammad Yasar and Behl, Marc and Lendlein, Andreas}, title = {Magneto-Mechanical Actuators with Reversible Stretching and Torsional Actuation Capabilities}, series = {MRS Advances}, volume = {4}, journal = {MRS Advances}, number = {19}, publisher = {Cambridge Univ. Press}, address = {New York}, issn = {2059-8521}, doi = {10.1557/adv.2019.123}, pages = {1057 -- 1065}, year = {2019}, abstract = {Composite actuators consisting of magnetic nanoparticles dispersed in a crystallizable multiphase polymer system can be remotely controlled by alternating magnetic fields (AMF). These actuators contain spatially segregated crystalline domains with chemically different compositions. Here, the crystalline domain associated to low melting transition range is responsible for actuation while the crystalline domain associated to the higher melting transition range determines the geometry of the shape change. This paper reports magnetomechanical actuators which are based on a single crystalline domain of oligo(omega-pentadecalactone) (OPDL) along with covalently integrated iron(III) oxide nanoparticles (ioNPs). Different geometrical modes of actuation such as a reversible change in length or twisting were implemented by a magneto-mechanical programming procedure. For an individual actuation mode, the degree of actuation could be tailored by variation of the magnetic field strengths. This material design can be easily extended to other composites containing other magnetic nanoparticles, e.g. with a high magnetic susceptibility.}, language = {en} } @article{BalkBehlLendlein2019, author = {Balk, Maria and Behl, Marc and Lendlein, Andreas}, title = {Hydrolytic Degradation of Actuators Based on Copolymer Networks From Oligo(epsilon-caprolactone) Dimethacrylate and n-Butyl Acrylate}, series = {MRS advances}, volume = {4}, journal = {MRS advances}, number = {21}, publisher = {Cambridge Univ. Press}, address = {New York}, issn = {2059-8521}, doi = {10.1557/adv.2019.202}, pages = {1193 -- 1205}, year = {2019}, abstract = {Shape-memory polymer actuators often contain crystallizable polyester segments. Here, the influence of accelerated hydrolytic degradation on the actuation performance in copolymer networks based on oligo(epsilon-caprolactone) dimethacrylate (OCL) and n-butyl acrylate is studied The semi-crystalline OCL was utilized as crosslinker with molecular weights of 2.3 and 15.2 kg.mol(-1) (ratio: 1:1 wt\%) and n-butyl acrylate (25 wt\% relative to OCL content) acted as softening agent creating the polymer main chain segments within the network architecture. The copolymer networks were programmed by 50\% elongation and were degraded by means of alkaline hydrolysis utilizing sodium hydroxide solution (pH = 13). Experiments were performed in the range of the broad melting range of the actuators at 40 degrees C. The degradation of test specimen was monitored by the sample mass, which was reduced by 25 wt\% within 105 d .45 degradation products, fragments of OCL with molecular masses ranging from 400 to 50.000 g.mol(-1) could be detected by NMR spectroscopy and GPC measurements. The cleavage of ester groups included in OCL segments resulted in a decrease of the melting temperature (T-m) related to the actuator domains (amorphous at the temperature of degradation) and simultaneously, the T-m associated to the skeleton domain was increased (semi-crystalline at the temperature of degradation). The alkaline hydrolysis decreased the polymer chain orientation of OCL domains until a random alignment of crystalline domains was obtained. This result was confirmed by cyclic thermomechanical actuation tests. The performance of directed movements decreased almost linearly as function of degradation time resulting in the loss of functionality when the orientation of polymer chains disappeared. Here, actuators were able to provide reversible movements until 91 d when the accelerated bulk degradation procedure using alkaline hydrolysis (pH = 13) was applied. Accordingly, a lifetime of more than one year can be guaranteed under physiological conditions (pH = 7.4) when, e.g., artificial muscles for biomimetic robots as potential application for these kind of shape-memory polymer actuators will be addressed.}, language = {en} } @article{KuhnlaReinthalerBrauneetal.2019, author = {Kuhnla, A. and Reinthaler, Markus and Braune, Steffen and Maier, A. and Pindur, Gerhard and Lendlein, Andreas and Jung, Friedrich}, title = {Spontaneous and induced platelet aggregation in apparently healthy subjects in relation to age}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {71}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {4}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-199006}, pages = {425 -- 435}, year = {2019}, abstract = {Thrombotic disorders remain the leading cause of mortality and morbidity, despite the fact that anti-platelet therapies and vascular implants are successfully used today. As life expectancy is increasing in western societies, the specific knowledge about processes leading to thrombosis in elderly is essential for an adequate therapeutic management of platelet dysfunction and for tailoring blood contacting implants. This study addresses the limited available data on platelet function in apparently healthy subjects in relation to age, particularly in view of subjects of old age (80-98 years). Apparently healthy subjects between 20 and 98 years were included in this study. Platelet function was assessed by light transmission aggregometry and comprised experiments on spontaneous as well as ristocetin-, ADP- and collagen-induced platelet aggregation. The data of this study revealed a non-linear increase in the maximum spontaneous platelet aggregation (from 3.3\% +/- 3.3\% to 10.9\% +/- 5.9\%). The maximum induced aggregation decreased with age for ristocetin (from 85.8\% +/- 7.2\% to 75.0\% +/- 7.8\%), ADP (from 88.5\% +/- 4.6\% to 64.8\% +/- 7.3\%) and collagen (from 89.5\% +/- 3.0\% to 64.0\% +/- 4.0\%) in a non-linear manner (linear regression analysis). These observations indicate that during aging, circulating platelets become increasingly activated but lose their full aggregatory potential, a phenomenon that was earlier termed "platelet exhaustion". In this study we extended the limited existing data for spontaneous and induced platelet aggregation of apparently healthy donors above the age of 75 years. The presented data indicate that the extrapolation of data from a middle age group does not necessarily predict platelet function in apparently healthy subjects of old age. It emphasizes the need for respective studies to improve our understanding of thrombotic processes in elderly humans.}, language = {en} } @article{DengZouWangetal.2019, author = {Deng, Zijun and Zou, Jie and Wang, Weiwei and Nie, Yan and Tung, Wing-Tai and Ma, Nan and Lendlein, Andreas}, title = {Dedifferentiation of mature adipocytes with periodic exposure to cold}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {71}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {4}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-199005}, pages = {415 -- 424}, year = {2019}, abstract = {Lipid-containing adipocytes can dedifferentiate into fibroblast-like cells under appropriate culture conditions, which are known as dedifferentiated fat (DFAT) cells. However, the relative low dedifferentiation efficiency with the established protocols limit their widespread applications. In this study, we found that adipocyte dedifferentiation could be promoted via periodic exposure to cold (10 degrees C) in vitro. The lipid droplets in mature adipocytes were reduced by culturing the cells in periodic cooling/heating cycles (10-37 degrees C) for one week. The periodic temperature change led to the down-regulation of the adipogenic genes (FABP4, Leptin) and up-regulation of the mitochondrial uncoupling related genes (UCP1, PGC-1 alpha, and PRDM16). In addition, the enhanced expression of the cell proliferation marker Ki67 was observed in the dedifferentiated fibroblast-like cells after periodic exposure to cold, as compared to the cells cultured in 37 degrees C. Our in vitro model provides a simple and effective approach to promote lipolysis and can be used to improve the dedifferentiation efficiency of adipocytes towards multipotent DFAT cells.}, language = {en} } @article{MazurekBudzynskaRazzaqBehletal.2019, author = {Mazurek-Budzynska, Magdalena and Razzaq, Muhammad Yasar and Behl, Marc and Lendlein, Andreas}, title = {Shape-Memory Polymers}, series = {Functional Polymers}, journal = {Functional Polymers}, publisher = {Springer}, address = {Cham}, isbn = {978-3-319-95987-0}, issn = {2510-3458}, doi = {10.1007/978-3-319-95987-0_18}, pages = {605 -- 663}, year = {2019}, abstract = {Shape-memory polymers (SMPs) are stimuli-sensitive materials capable of changing their shape on demand. A shape-memory function is a result of the polymer architecture together with the application of a specific programming procedure. Various possible mechanisms to induce the shape-memory effect (SME) can be realized, which can be based on thermal transitions of switching domains or on reversible molecular switches (e.g., supramolecular interactions, reversible covalent bonds). Netpoints, which connect the switching domains and determine the permanent shape, can be either provided by covalent bonds or by physical intermolecular interactions, such as hydrogen bonds or crystallites. This chapter reviews different ways of implementing the phenomenon of programmable changes in the polymer shape, including the one-way shape-memory effect (1-W SME), triple-and multi-shape effects (TSE/ MSE), the temperature-memory effect (TME), and reversible shape-memory effects, which can be realized in constant stress conditions (rSME), or in stress-free conditions (reversible bidirectional shape-memory effect (rbSME)). Furthermore, magnetically actuated SMPs and shape-memory hydrogels (SMHs) are described to show the potential of the SMP technology in biomedical applications and multifunctional approaches.}, language = {en} } @article{FolikumahNeffeBehletal.2019, author = {Folikumah, Makafui Yao and Neffe, Axel T. and Behl, Marc and Lendlein, Andreas}, title = {Thiol Michael-Type reactions of optically active mercapto-acids in aqueous medium}, series = {MRS advances : a journal of the Materials Research Society}, volume = {4}, journal = {MRS advances : a journal of the Materials Research Society}, number = {46-47}, publisher = {Springer Nature Switzerland AG}, address = {Cham}, issn = {2059-8521}, doi = {10.1557/adv.2019.308}, pages = {2515 -- 2525}, year = {2019}, abstract = {Defined chemical reactions in a physiological environment are a prerequisite for the in situ synthesis of implant materials potentially serving as matrix for drug delivery systems, tissue fillers or surgical glues. 'Click' reactions like thiol Michael-type reactions have been successfully employed as bioorthogonal reaction. However, due to the individual stereo-electronic and physical properties of specific substrates, an exact understanding their chemical reactivity is required if they are to be used for in-situ biomaterial synthesis. The chiral (S)-2-mercapto-carboxylic acid analogues of L-phenylalanine (SH-Phe) and L-leucine (SH-Leu) which are subunits of certain collagenase sensitive synthetic peptides, were explored for their potential for in-situ biomaterial formation via the thiol Michael-type reaction. In model reactions were investigated the kinetics, the specificity and influence of stereochemistry of this reaction. We could show that only reactions involving SH-Leu yielded the expected thiol-Michael product. The inability of SH-Phe to react was attributed to the steric hindrance of the bulky phenyl group. In aqueous media, successful reaction using SH-Leu is thought to proceed via the sodium salt formed in-situ by the addition of NaOH solution, which was intented to aid the solubility of the mercapto-acid in water. Fast reaction rates and complete acrylate/maleimide conversion were only realized at pH 7.2 or higher suggesting the possible use of SH-Leu under physiological conditions for thiol Michael-type reactions. This method of in-situ formed alkali salts could be used as a fast approach to screen mercapto-acids for thio Michael-type reactions without the synthesis of their corresponding esters.}, language = {en} } @article{FriessWischkeLendlein2019, author = {Friess, Fabian and Wischke, Christian and Lendlein, Andreas}, title = {Microscopic analysis of shape-shiftable oligo(epsilon-caprolactone)-based particles}, series = {MRS advances}, volume = {4}, journal = {MRS advances}, number = {59-60}, publisher = {Cambridge Univ. Press}, address = {New York}, issn = {2059-8521}, doi = {10.1557/adv.2019.392}, pages = {3199 -- 3206}, year = {2019}, abstract = {Spherical particles are routinely monitored and described by hydrodynamic diameters determined, e.g., by light scattering techniques. Non-spherical particles such as prolate ellipsoids require alternative techniques to characterize particle size as well as particle shape. In this study, oligo(epsilon-caprolactone) (oCL) based micronetwork (MN) particles with a shape-shifting function based on their shape-memory capability were programmed from spherical to prolate ellipsoidal shape aided by incorporation and stretching in a water-soluble phantom matrix. By applying light microscopy with automated contour detection and aspect ratio analysis, differences in characteristic aspect ratio distributions of non-crosslinked microparticles (MPs) and crosslinked MNs were detected when the degrees of phantom elongation (30-290\%) are increased. The thermally induced shape recovery of programmed MNs starts in the body rather than from the tips of ellipsoids, which may be explained based on local differences in micronetwork deformation. By this approach, fascinating intermediate particle shapes with round bodies and two opposite sharp tips can be obtained, which could be of interest, e.g., in valves or other technical devices, in which the tips allow to temporarily encage the switchable particle in the desired position.}, language = {en} } @article{LendleinGould2019, author = {Lendlein, Andreas and Gould, Oliver E. C.}, title = {Reprogrammable recovery and actuation behaviour of shape-memory polymers}, series = {Nature reviews. Materials}, volume = {4}, journal = {Nature reviews. Materials}, number = {2}, publisher = {Nature Publ. Group}, address = {London}, issn = {2058-8437}, doi = {10.1038/s41578-018-0078-8}, pages = {116 -- 133}, year = {2019}, abstract = {Shape memory is the capability of a material to be deformed and fixed into a temporary shape. Recovery of the original shape can then be triggered only by an external stimulus. Shape-memory polymers are highly deformable materials that can be programmed to recover a memorized shape in response to a variety of environmental and spatially localized stimuli as a one-way effect. The shape-memory function can also be generated as a reversible effect enabling actuation behaviour through macroscale deformation and processing, specifically by dictating the macromolecular orientation of actuation units and of the skeleton structure of geometry-determining units in the polymers. Shape-memory polymers can be programmed and reprogrammed into arbitrary shapes. Both recovery and actuation behaviour are reprogrammable. In this Review, we outline the common basis and key differences between the two shape-memory behaviours of polymers in terms of mechanism, fabrication schemes and characterization methods. We discuss which combination of macromolecular architecture and macroscale processing is necessary for coordinated, decentralized and responsive physical behaviour. The extraction of relevant thermomechanical information is described, and design criteria are shown for microscale and macroscale morphologies to gain high levels of recovered or actuation strains as well as on-demand 2D-to-3D shape transformations. Finally, real-world applications and key future challenges are highlighted.}, language = {en} } @article{JiangMansfeldFangetal.2018, author = {Jiang, Yi and Mansfeld, Ulrich and Fang, Liang and Kratz, Karl and Lendlein, Andreas}, title = {Temperature-induced evolution of microstructures on poly[ethylene-co-(vinyl acetate)] substrates switches their underwater wettability}, series = {Materials \& design}, volume = {163}, journal = {Materials \& design}, publisher = {Elsevier}, address = {Oxford}, issn = {0264-1275}, doi = {10.1016/j.matdes.2018.12.002}, pages = {10}, year = {2018}, abstract = {Material surfaces with tailored aerophobicity are crucial for applications where gas bubble wettability has to be controlled, e.g., gas storage and transport, electrodes, bioreactors or medical devices. Here, we present switchable underwater aerophobicity of hydrophobic polymeric substrates, which respond to heat with multilevel micro-and nanotopographical changes. The cross-linked poly[ethylene-co-(vinyl acetate)] substrates possess arrays of microcylinders with a nanorough top surface. It is hypothesized that the specific micro-/nanotopography of the surface allows trapping of a water film at the micro interspace and in this way generates the aerophobic behavior. The structured substrates were programmed to a temporarily stable, nanoscale flat substrate showing aerophilic behavior. Upon heating, the topographical changes caused a switch in contact angle from aerophilic to aerophobic for approaching air bubbles. In this way, the initial adhesion of air bubbles to the programmed flat substrate could be turned into repellence for the recovered substrate surface. The temperature at which the repellence of air bubbles starts can be adjusted from 58 +/- 3 degrees C to 73 +/- 3 degrees C by varying the deformation temperature applied during the temperature-memory programming procedure. The presented actively switching polymeric substrates are attractive candidates for applications, where an on-demand gas bubble repellence is advantageous. (c) 2018 Helmholtz-Zentrum Geesthacht, Zentrum fur Material- und Kustenforschung. Published by Elsevier Ltd.}, language = {en} } @article{BhuvaneshMachatschekLysyakovaetal.2019, author = {Bhuvanesh, Thanga and Machatschek, Rainhard Gabriel and Lysyakova, Liudmila and Kratz, Karl and Schulz, Burkhard and Ma, Nan and Lendlein, Andreas}, title = {Collagen type-IV Langmuir and Langmuir-Schafer layers as model biointerfaces to direct stem cell adhesion}, series = {Biomedical materials : materials for tissue engineering and regenerative medicine}, volume = {14}, journal = {Biomedical materials : materials for tissue engineering and regenerative medicine}, number = {2}, publisher = {Inst. of Physics Publ.}, address = {Bristol}, issn = {1748-6041}, doi = {10.1088/1748-605X/aaf464}, pages = {17}, year = {2019}, abstract = {In biomaterial development, the design of material surfaces that mimic the extra-cellular matrix (ECM) in order to achieve favorable cellular instruction is rather challenging. Collagen-type IV (Col-IV), the major scaffolding component of Basement Membranes (BM), a specialized ECM with multiple biological functions, has the propensity to form networks by self-assembly and supports adhesion of cells such as endothelial cells or stem cells. The preparation of biomimetic Col-IV network-like layers to direct cell responses is difficult. We hypothesize that the morphology of the layer, and especially the density of the available adhesion sites, regulates the cellular adhesion to the layer. The Langmuir monolayer technique allows for preparation of thin layers with precisely controlled packing density at the air-water (A-W) interface. Transferring these layers onto cell culture substrates using the Langmuir-Schafer (LS) technique should therefore provide a pathway for preparation of BM mimicking layers with controlled cell adherence properties. In situ characterization using ellipsometry and polarization modulation-infrared reflection absorption spectroscopy of Col-IV layer during compression at the A-W interface reveal that there is linear increase of surface molecule concentration with negligible orientational changes up to a surface pressure of 25 mN m(-1). Smooth and homogeneous Col-IV network-like layers are successfully transferred by LS method at 15 mN m(-1) onto poly(ethylene terephthalate) (PET), which is a common substrate for cell culture. In contrast, the organization of Col-IV on PET prepared by the traditionally employed solution deposition method results in rather inhomogeneous layers with the appearance of aggregates and multilayers. Progressive increase in the number of early adherent mesenchymal stem cells (MSCs) after 24 h by controlling the areal Col-IV density by LS transfer at 10, 15 and 20 mN m(-1) on PET is shown. The LS method offers the possibility to control protein characteristics on biomaterial surfaces such as molecular density and thereby, modulate cell responses.}, language = {en} } @article{JiangMansfeldKratzetal.2019, author = {Jiang, Yi and Mansfeld, Ulrich and Kratz, Karl and Lendlein, Andreas}, title = {Programmable microscale stiffness pattern of flat polymeric substrates by temperature-memo technology}, series = {MRS Communications}, volume = {9}, journal = {MRS Communications}, number = {1}, publisher = {Cambridge Univ. Press}, address = {New York}, issn = {2159-6859}, doi = {10.1557/mrc.2019.24}, pages = {181 -- 188}, year = {2019}, abstract = {Temperature-memory technology was utilized to generate flat substrates with a programmable stiffness pattern from cross-linked poly(ethylene-co-vinyl acetate) substrates with cylindrical microstructures. Programmed substrates were obtained by vertical compression at temperatures in the range from 60 to 100 degrees C and subsequent cooling, whereby a flat substrate was achieved by compression at 72 degrees C, as documented by scanning electron microscopy and atomic force microscopy (AFM). AFM nanoindentation experiments revealed that all programmed substrates exhibited the targeted stiffness pattern. The presented technology for generating polymeric substrates with programmable stiffness pattern should be attractive for applications such as touchpads. optical storage, or cell instructive substrates.}, language = {en} } @article{MazurekBudzyńskaBehlRazzaqetal.2019, author = {Mazurek-Budzyńska, Magdalena and Behl, Marc and Razzaq, Muhammad Yasar and N{\"o}chel, Ulrich and Rokicki, Gabriel and Lendlein, Andreas}, title = {Hydrolytic stability of aliphatic poly(carbonate-urea-urethane)s: Influence of hydrocarbon chain length in soft segment}, series = {Polymer Degradation and Stability}, volume = {161}, journal = {Polymer Degradation and Stability}, publisher = {Elsevier}, address = {Oxford}, issn = {0141-3910}, pages = {283 -- 297}, year = {2019}, abstract = {Poly(carbonate-urethane)s (PCUs) exhibit improved resistance to hydrolytic degradation and in vivo stress cracking compared to poly(ester-urethane)s and their degradation leads to lower inflammation of the surrounding tissues. Therefore, PCUs are promising implant materials and are considered for devices such as artificial heart or spine implants. In this work, the hydrolytic stability of different poly(carbonate-urethane-urea)s (PCUUs) was studied under variation of the length of hydrocarbon chain (6, 9, 10, and 12 methylene units) between the carbonate linkages in the precursors. PCUUs were synthesized from isophorone diisocyanate and oligo(alkylene carbonate) diols using the moisture-cure method. The changes of sample weight, thermal and mechanical properties, morphology, as well as the degradation products after immersion in a buffer solution (PBS, pH = 7.4) for up to 10 weeks at 37 degrees C were monitored and analyzed. In addition, mechanical properties after 20 weeks (in PBS, 37 degrees C) were investigated. The gel content was determined based on swelling experiments in chloroform. Based on the DSC analysis, slight increases of melting transitions of PCUUs were observed, which were attributed to structure reorganization related to annealing at 37 degrees C rather than to the degradation of the PCUU. Tensile strength after 20 weeks of all investigated samples remained in the range of 29-39 MPa, whereas the elongation at break e(m) decreased only slightly and remained in the range between 670 and 800\%. Based on the characterization of degradation products after up to 10 weeks of immersion it was assessed that oligomers are mainly consisting of hard segments containing urea linkages, which could be assigned to hindered-urea dissociation mechanism. The investigations confirmed good resistance of PCUUs to hydrolysis. Only minor changes in the crystallinity, as well as thermal and mechanical properties were observed and depended on hydrocarbon chain length in soft segment of PCUUs. (C) 2019 Published by Elsevier Ltd.}, language = {en} } @article{LuetzowHommesSchattmannNeffeetal.2018, author = {L{\"u}tzow, Karola and Hommes-Schattmann, Paul J. and Neffe, Axel T. and Ahmad, Bilal and Williams, Gareth R. and Lendlein, Andreas}, title = {Perfluorophenyl azide functionalization of electrospun poly(para-dioxanone)}, series = {Polymers for advanced technologies}, volume = {30}, journal = {Polymers for advanced technologies}, number = {5}, publisher = {Wiley}, address = {Hoboken}, issn = {1042-7147}, doi = {10.1002/pat.4331}, pages = {1165 -- 1172}, year = {2018}, abstract = {Strategies to surface-functionalize scaffolds by covalent binding of biologically active compounds are of fundamental interest to control the interactions between scaffolds and biomolecules or cells. Poly(para-dioxanone) (PPDO) is a clinically established polymer that has shown potential as temporary implant, eg, for the reconstruction of the inferior vena cava, as a nonwoven fiber mesh. However, PPDO lacks suitable chemical groups for covalent functionalization. Furthermore, PPDO is highly sensitive to hydrolysis, reflected by short in vivo half-life times and degradation during storage. Establishing a method for covalent functionalization without degradation of this hydrolyzable polymer is therefore important to enable the surface tailoring for tissue engineering applications. It was hypothesized that treatment of PPDO with an N-hydroxysuccinimide ester group bearing perfluorophenyl azide (PFPA) under UV irradiation would allow efficient surface functionalization of the scaffold. X-ray photoelectron spectroscopy and attenuated total reflectance Fourier-transformed infrared spectroscopy investigation revealed the successful binding, while a gel permeation chromatography study showed that degradation did not occur under these conditions. Coupling of a rhodamine dye to the N-hydroxysuccinimide esters on the surface of a PFPA-functionalized scaffold via its amine linker showed a homogenous staining of the PPDO in laser confocal microscopy. The PFPA method is therefore applicable even to the surface functionalization of hydrolytically labile polymers, and it was demonstrated that PFPA chemistry may serve as a versatile tool for the (bio-)functionalization of PPDO scaffolds.}, language = {en} } @article{BalkBehlLendlein2019, author = {Balk, Maria and Behl, Marc and Lendlein, Andreas}, title = {Quadruple-shape hydrogels}, series = {Smart materials and structures}, volume = {28}, journal = {Smart materials and structures}, number = {5}, publisher = {IOP Publ. Ltd.}, address = {Bristol}, issn = {0964-1726}, doi = {10.1088/1361-665X/ab0e91}, pages = {10}, year = {2019}, abstract = {The capability of directed movements by two subsequent shape changes could be implemented in shape-memory hydrogels by incorporation of two types of crystallizable side chains While in non-swollen polymer networks even more directed movements could be realized, the creation of multi-shape hydrogels is still a challenge. We hypothesize that a quadruple-shape effect in hydrogels can be realized, when a swelling capacity almost independent of temperature is generated, whereby directed movements could be enabled, which are not related to swelling. In this case, entropy elastic recovery could be realized by hydrophilic segments and the fixation of different macroscopic shapes by means of three semi-crystalline side chains generating temporary crosslinks. Monomethacrylated semi-crystalline oligomers were connected as side chains in a hydrophilic polymer network via radical copolymerization. Computer assisted modelling was utilized to design a demonstrator capable of complex shape shifts by creating a casting mold via 3D printing from polyvinyl alcohol. The demonstrator was obtained after copolymerization of polymer network forming components within the mold, which was subsequently dissolved in water. A thermally-induced quadruple-shape effect was realized after equilibrium swelling of the polymer network in water. Three directed movements were successfully obtained when the temperature was continuously increased from 5 degrees C to 90 degrees C with a recovery ratio of the original shape above 90\%. Hence, a thermally-induced quadruple-shape effect as new record for hydrogels was realized. Here, the temperature range for the multi-shape effect was limited by water as swelling media (0 degrees C-100 degrees C), simultaneously distinctly separated thermal transitions were required, and the overall elasticity indispensable for successive deformations was reduced as result of partially chain segment orientation induced by swelling in water. Conclusively the challenges for penta- or hexa-shape gels are the design of systems enabling higher elastic deformability and covering a larger temperature range by switching to a different solvent.}, language = {en} } @article{ZhangRudolphBenitezetal.2019, author = {Zhang, Quanchao and Rudolph, Tobias and Benitez, Alejandro J. and Gould, Oliver E. C. and Behl, Marc and Kratz, Karl and Lendlein, Andreas}, title = {Temperature-controlled reversible pore size change of electrospun fibrous shape-memory polymer actuator based meshes}, series = {Smart materials and structures}, volume = {28}, journal = {Smart materials and structures}, number = {5}, publisher = {IOP Publ. Ltd.}, address = {Bristol}, issn = {0964-1726}, doi = {10.1088/1361-665X/ab10a1}, pages = {10}, year = {2019}, abstract = {Fibrous membranes capable of dynamically responding to external stimuli are highly desirable in textiles and biomedical materials, where adaptive behavior is required to accommodate complex environmental changes. For example, the creation of fabrics with temperature-dependent moisture permeability or self-regulating membranes for air filtration is dependent on the development of materials that exhibit a reversible stimuli-responsive pore size change. Here, by imbuing covalently crosslinked poly(ε-caprolactone) (cPCL) fibrous meshes with a reversible bidirectional shape-memory polymer actuation (rbSMPA) we create a material capable of temperature-controlled changes in porosity. Cyclic thermomechanical testing was used to characterize the mechanical properties of the meshes, which were composed of randomly arranged microfibers with diameters of 2.3 ± 0.6 μm giving an average pore size of approx. 10 μm. When subjected to programming strains of εm = 300\% and 100\% reversible strain changes of εʹrev = 22\% ± 1\% and 6\% ± 1\% were measured, with switching temperature ranges of 10 °C-30 °C and 45 °C-60 °C for heating and cooling, respectively. The rbSMPA of cPCL fibrous meshes generated a microscale reversible pore size change of 11\% ± 3\% (an average of 1.5 ± 0.6 μm), as measured by scanning electron microscopy. The incorporation of a two-way shape-memory actuation capability into fibrous meshes is anticipated to advance the development and application of smart membrane materials, creating commercially viable textiles and devices with enhanced performance and novel functionality.}, language = {en} } @article{BrunacciNeffeWischkeetal.2019, author = {Brunacci, Nadia and Neffe, Axel T. and Wischke, Christian and Naolou, Toufik and N{\"o}chel, Ulrich and Lendlein, Andreas}, title = {Oligodepsipeptide (nano)carriers}, series = {Journal of controlled release}, volume = {301}, journal = {Journal of controlled release}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0168-3659}, doi = {10.1016/j.jconrel.2019.03.004}, pages = {146 -- 156}, year = {2019}, abstract = {High drug loads of nanoparticles are essential to efficiently provide a desired dosage in the required timeframe, however, these conditions may not be reached with so far established degradable matrices. Our conceptual approach for increasing the drug load is based on strengthening the affinity between drug and matrix in combination with stabilizing drug-matrix-hybrids through strong intermolecular matrix interactions. Here, a method for designing such complex drug-matrix hybrids is introduced employing computational methods (molecular dynamics and docking) as well as experimental studies (affinity, drug loading and distribution, drug release from films and nanoparticles). As model system, dexamethasone (DXM), relevant for the treatment of inflammatory diseases, in combination with poly[(rac-lactide)-co-glycolide] (PLGA) as standard degradable matrix or oligo[(3-(S)-sec-butyl) morpholine-2,5-dione] diol (OBMD) as matrix with hypothesized stronger interaction with DXM were investigated. Docking studies predicted higher affinity of DXM to OBMD than PLGA and displayed amide bond participation in hydrogen bonding with OBMD. Experimental investigations on films and nanoparticles, i.e. matrices of different shapes and sizes, confirmed this phenomenon as shown e.g. by a similar to 10 times higher solid state solubility of DXM in OBMD than in PLGA. DXM-loaded particles of similar to 150 nm prepared by nanoprecipitation in aqueous environment had a drug loading (DL) up to 16 times higher when employing OBMD as matrix compared to PLGA carriers due to enhanced drug retention in the OBMD phase. Importantly, drug relase periods were not altered as the release from films and particles was mainly ruled by the diffusion length as well as matrix degradation rather than the matrix type, which can be assigned to water diffusing into the matrix and breaking up of drug-matrix hydrogen bonds. Overall, the presented design and fabrication scheme showed predictive power and might universally enable the screening of drug/matrix interactions particularly to expand the oligodepsipeptide platform technology, e.g. by varying the depsipeptide side chains, for drug carrier and release systems.}, language = {en} } @article{NaolouLendleinNeffe2019, author = {Naolou, Toufik and Lendlein, Andreas and Neffe, Axel T.}, title = {Amides as non-polymerizable catalytic adjuncts enable the ring-opening polymerization of lactide with ferrous acetate under mild conditions}, series = {Frontiers in Chemistry}, volume = {7}, journal = {Frontiers in Chemistry}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {2296-2646}, doi = {10.3389/fchem.2019.00346}, pages = {12}, year = {2019}, abstract = {Sn-based catalysts are effective in the ring-opening polymerization (ROP) but are toxic. Fe(OAc)(2) used as an alternative catalyst is suitable for the ROP of lactide only at higher temperatures (>170 degrees C), associated with racemization. In the ROP of ester and amide group containing morpholinediones with Fe(OAc)(2) to polydepsipeptides at 135 degrees C, ester bonds were selectively opened. Here, it was hypothesized that ROP of lactones is possible with Fe(OAc)(2) when amides are present in the reactions mixture as Fe-ligands could increase the solubility and activity of the metal catalytic center. The ROP of lactide in the melt with Fe(OAc)(2) is possible at temperatures as low as 105 degrees C, in the presence of N-ethylacetamide or N-rnethylbenzamide as non-polymerizable catalytic adjuncts (NPCA), with high conversion (up to 99 mol\%) and yield (up to 88 mol\%). Polydispersities of polylactide decreased with decreasing reaction temperature to <= 1.1. NMR as well as polarimetric studies showed that no racemization occurred at reaction temperatures <= 145 degrees C. A kinetic study demonstrated a living chain-growth mechanism. MALDI analysis revealed that no side reactions (e.g., cyclization) occurred, though transesterification took place.}, language = {en} } @article{YuanNeriZakrietal.2019, author = {Yuan, Jinkai and Neri, Wilfrid and Zakri, Cecile and Merzeau, Pascal and Kratz, Karl and Lendlein, Andreas and Poulin, Philippe}, title = {Shape memory nanocomposite fibers for untethered high-energy microengines}, series = {Science}, volume = {365}, journal = {Science}, number = {6449}, publisher = {American Assoc. for the Advancement of Science}, address = {Washington}, issn = {0036-8075}, doi = {10.1126/science.aaw3722}, pages = {155 -- 158}, year = {2019}, abstract = {Classic rotating engines are powerful and broadly used but are of complex design and difficult to miniaturize. It has long remained challenging to make large-stroke, high-speed, high-energy microengines that are simple and robust. We show that torsionally stiffened shape memory nanocomposite fibers can be transformed upon insertion of twist to store and provide fast and high-energy rotations. The twisted shape memory nanocomposite fibers combine high torque with large angles of rotation, delivering a gravimetric work capacity that is 60 times higher than that of natural skeletal muscles. The temperature that triggers fiber rotation can be tuned. This temperature memory effect provides an additional advantage over conventional engines by allowing for the tunability of the operation temperature and a stepwise release of stored energy.}, language = {en} }