@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{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{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{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{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{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{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{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{BhaskarMaLendleinetal.2015,
  author    = {Bhaskar, Thanga Bhuvanesh Vijaya and Ma, Nan and Lendlein, Andreas and Roch, Toralf},
  title     = {The interaction of human macrophage subsets with silicone as a biomaterial},
  series = {Clinical hemorheology and microcirculation : blood flow and vessels},
  volume    = {61},
  journal   = {Clinical hemorheology and microcirculation : blood flow and vessels},
  number    = {2},
  publisher = {IOS Press},
  address   = {Amsterdam},
  issn      = {1386-0291},
  doi       = {10.3233/CH-151991},
  pages     = {119 -- 133},
  year      = {2015},
  abstract  = {Silicones are widely used as biomaterials for medical devices such as extracorporeal equipments. However, there is often conflicting evidence about their supposed cell-and histocompatibility. Macrophages could mediate silicone-induced adverse responses such as foreign body reaction and fibrous encapsulation. The polarization behaviour of macrophages could determine the clinical outcome after implantation of biomaterials. Induction of classically activated macrophages (CAM) may induce and support uncontrolled inflammatory responses and undesired material degradation. In contrast, polarization into alternatively activated macrophages (AAM) is assumed to support healing processes and implant integration. This study compared the interaction of non-polarized macrophages (M0), CAM, and AAM with commercially available tissue culture polystyrene (TCP) and a medical grade silicone-based biomaterial, regarding the secretion of inflammatory mediators such as cytokines and chemokines. Firstly, by using the Limulus amoebocyte lysate (LAL) test the silicone films were shown to be free of soluble endotoxins, which is the prerequisite to investigate their interaction with primary immune cells. Primary human monocyte-derived macrophages (M0) were polarized into CAM and AAM by addition of suitable differentiation factors. These macrophage subsets were incubated on the materials for 24 hours and their viability and cytokine secretion was assessed. In comparison to TCP, cell adhesion was lower on silicone after 24 hours for all three macrophage subsets. However, compared to TCP, silicone induced higher levels of certain inflammatory and chemotactic cytokines in M0, CAM, and AAM macrophage subsets. Conclusively, it was shown that silicone has the ability to induce a pro-inflammatory state to different magnitudes dependent on the macrophage subsets. This priming of the macrophage phenotype by silicone could explain the incidence of severe foreign body complications observed in vivo.},
  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{BhuvaneshSaretiaRochetal.2017,
  author    = {Bhuvanesh, Thanga and Saretia, Shivam and Roch, Toralf and Sch{\"o}ne, Anne-Christin and Rottke, Falko O. and Kratz, Karl and Wang, Weiwei and Ma, Nan and Schulz, Burkhard and Lendlein, Andreas},
  title     = {Langmuir-Schaefer films of fibronectin as designed biointerfaces for culturing stem cells},
  series = {Polymers for advanced technologies},
  volume    = {28},
  journal   = {Polymers for advanced technologies},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1042-7147},
  doi       = {10.1002/pat.3910},
  pages     = {1305 -- 1311},
  year      = {2017},
  abstract  = {Glycoproteins adsorbing on an implant upon contact with body fluids can affect the biological response in vitro and in vivo, depending on the type and conformation of the adsorbed biomacromolecules. However, this process is poorly characterized and so far not controllable. Here, protein monolayers of high molecular cohesion with defined density are transferred onto polymeric substrates by the Langmuir-Schaefer (LS) technique and were compared with solution deposition (SO) method. It is hypothesized that on polydimethylsiloxane (PDMS), a substrate with poor cell adhesion capacity, the fibronectin (FN) layers generated by the LS and SO methods will differ in their organization, subsequently facilitating differential stem cell adhesion behavior. Indeed, atomic force microscopy visualization and immunofluorescence images indicated that organization of the FN layer immobilized on PDMS was uniform and homogeneous. In contrast, FN deposited by SO method was rather heterogeneous with appearance of structures resembling protein aggregates. Human mesenchymal stem cells showed reduced absolute numbers of adherent cells, and the vinculin expression seemed to be higher and more homogenously distributed after seeding on PDMS equipped with FN by LS in comparison with PDMS equipped with FN by SO. These divergent responses could be attributed to differences in the availability of adhesion molecule ligands such as the Arg-Gly-Asp (RGD) peptide sequence presented at the interface. The LS method allows to control the protein layer characteristics, including the thickness and the protein orientation or conformation, which can be harnessed to direct stem cell responses to defined outcomes, including migration and differentiation. Copyright (c) 2016 John Wiley \& Sons, Ltd.},
  language  = {en}
}
@article{BinzenLendleinKelchetal.2004,
  author    = {Binzen, Eva and Lendlein, Andreas and Kelch, S. and Rickert, D. and Franke, R. P.},
  title     = {Biomaterial-microvasculature interaction on polymers after implantation in mice},
  year      = {2004},
  language  = {en}
}
@article{BlockiLoewenbergJiangetal.2017,
  author    = {Blocki, Anna and L{\"o}wenberg, Candy and Jiang, Yi and Kratz, Karl and Neffe, Axel T. and Jung, Friedrich and Lendlein, Andreas},
  title     = {Response of encapsulated cells to a gelatin matrix with varied bulk and microenvironmental elastic properties},
  series = {Polymers for advanced technologies},
  volume    = {28},
  journal   = {Polymers for advanced technologies},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1042-7147},
  doi       = {10.1002/pat.3947},
  pages     = {1245 -- 1251},
  year      = {2017},
  abstract  = {Gelatin-based hydrogels offer various biochemical cues that support encapsulated cells and are therefore suitable as cell delivery vehicles in regenerative medicine. However, besides the biochemical signals, biomechanical cues are crucial to ensure an optimal support of encapsulated cells. Hence, we aimed to correlate the cellular response of encapsulated cells to macroscopic and microscopic elastic properties of glycidylmethacrylate (GMA)-functionalized gelatin-based hydrogels. To ensure that different observations in cellular behavior could be attributed to differences in elastic properties, an identical concentration as well as degree of functionalization of biopolymers was utilized to form covalently crosslinked hydrogels. Elastic properties were merely altered by varying the average gelatin-chain length. Hydrogels exhibited an increased degree of swelling and a decreased bulk elastic modulus G with prolonged autoclaving of the starting solution. This was accompanied by an increase of hydrogel mesh size and thus by a reduction of crosslinking density. Tougher hydrogels retained the largest amount of cells; however, they also interfered with cell viability. Softer gels contained a lower cell density, but supported cell elongation and viability. Observed differences could be partially attributed to differences in bulk properties, as high crosslinking densities interfere with diffusion and cell spreading and thus can impede cell viability. Interestingly, a microscopic elastic modulus in the range of native soft tissue supported cell viability and elongation best while ensuring a good cell entrapment. In conclusion, gelatin-based hydrogels providing a soft tissue-like microenvironment represent adequate cell delivery vehicles for tissue engineering approaches. Copyright (c) 2016 John Wiley \& Sons, Ltd.},
  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{BrauneFroehlichLendleinetal.2016,
  author    = {Braune, Steffen and Froehlich, G. M. and Lendlein, Andreas and Jung, Friedrich},
  title     = {Effect of temperature on platelet adherence},
  series = {Clinical hemorheology and microcirculation : blood flow and vessels},
  volume    = {61},
  journal   = {Clinical hemorheology and microcirculation : blood flow and vessels},
  publisher = {IOS Press},
  address   = {Amsterdam},
  issn      = {1386-0291},
  doi       = {10.3233/CH-152028},
  pages     = {681 -- 688},
  year      = {2016},
  abstract  = {BACKGROUND: Thrombogenicity is one of the main parameters tested in vitro to evaluate the hemocompatibility of artificial surfaces. While the influence of the temperature on platelet aggregation has been addressed by several studies, the temperature influence on the adherence of platelets to body foreign surfaces as an important aspect of biomedical device handling has not yet been explored. Therefore, we analyzed the influence of two typically applied incubation-temperatures (22 degrees C and 37 degrees C) on the adhesion of platelets to biomaterials. MATERIAL AND METHODS: Thrombogenicity of three different polymers - medical grade poly(dimethyl siloxane) (PDMS), polytetrafluoroethylene (PTFE) and polyethylene terephthalate (PET) - were studied in an in vitro static test. Platelet adhesion was studied with stringently characterized blood from apparently healthy subjects. Collection of whole blood and preparation of platelet rich plasma (PRP) was carried out at room temperature (22 degrees C). PRP was incubated with the polymers either at 22 degrees C or 37 degrees C. Surface adherent platelets were fixed, fluorescently labelled and assessed by an image-based approach. RESULTS AND DISCUSSION: Differences in the density of adherent platelets after incubation at 22 degrees C and 37 degrees C occurred on PDMS and PET. Similar levels of adherent platelets were observed on the very thrombogenic PTFE. The covered surface areas per single platelet were analyzed to measure the state of platelet activation and revealed no differences between the two incubation temperatures for any of the analyzed polymers. Irrespective of the observed differences between the low and medium thrombogenic PDMS and PET and the higher variability at 22 degrees C, the thrombogenicity of the three investigated polymers was evaluated being comparable at both incubation temperatures.},
  language  = {en}
}
@article{BrauneGrossWalteretal.2016,
  author    = {Braune, Steffen and Gross, M. and Walter, M. and Zhou, Shengqiang and Dietze, Siegfried and Rutschow, S. and Lendlein, Andreas and Tschoepe, C. and Jung, Friedrich},
  title     = {Adhesion and activation of platelets from subjects with coronary artery disease and apparently healthy individuals on biomaterials},
  series = {Journal of biomedical materials research : an official journal of the Society for Biomaterials, the Japanese Society for Biomaterials; the Australian Society for Biomaterials},
  volume    = {104},
  journal   = {Journal of biomedical materials research : an official journal of the Society for Biomaterials, the Japanese Society for Biomaterials; the Australian Society for Biomaterials},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {1552-4973},
  doi       = {10.1002/jbm.b.33366},
  pages     = {210 -- 217},
  year      = {2016},
  abstract  = {On the basis of the clinical studies in patients with coronary artery disease (CAD) presenting an increased percentage of activated platelets, we hypothesized that hemocompatibility testing utilizing platelets from healthy individuals may result in an underestimation of the materials' thrombogenicity. Therefore, we investigated the interaction of polymer-based biomaterials with platelets from CAD patients in comparison to platelets from apparently healthy individuals. In vitro static thrombogenicity tests revealed that adherent platelet densities and total platelet covered areas were significantly increased for the low (polydimethylsiloxane, PDMS) and medium (Collagen) thrombogenic surfaces in the CAD group compared to the healthy subjects group. The area per single platelet—indicating the spreading and activation of the platelets—was markedly increased on PDMS treated with PRP from CAD subjects. This could not be observed for collagen or polytetrafluoroethylene (PTFE). For the latter material, platelet adhesion and surface coverage did not differ between the two groups. Irrespective of the substrate, the variability of these parameters was increased for CAD patients compared to healthy subjects. This indicates a higher reactivity of platelets from CAD patients compared to the healthy individuals. Our results revealed, for the first time, that utilizing platelets from apparently healthy donors bears the risk of underestimating the thrombogenicity of polymer-based biomaterials.},
  language  = {en}
}
@article{BrauneWalterSchulzeetal.2014,
  author    = {Braune, Steffen and Walter, M. and Schulze, F. and Lendlein, Andreas and Jung, Friedrich},
  title     = {Changes in platelet morphology and function during 24 hours of storage},
  series = {Clinical hemorheology and microcirculation : blood flow and vessels},
  volume    = {58},
  journal   = {Clinical hemorheology and microcirculation : blood flow and vessels},
  number    = {1},
  publisher = {IOS Press},
  address   = {Amsterdam},
  issn      = {1386-0291},
  doi       = {10.3233/CH-141876},
  pages     = {159 -- 170},
  year      = {2014},
  abstract  = {For in vitro studies assessing the interaction of platelets with implant materials, common and standardized protocols for the preparation of platelet rich plasma (PRP) are lacking, which may lead to non-matching results due to the diversity of applied protocols. Particularly, the aging of platelets during prolonged preparation and storage times is discussed to lead to an underestimation of the material thrombogenicity. Here, we study the influence of whole blood-and PRP-storage times on changes in platelet morphology and function. Whole blood PFA100 closure times increased after stimulation with collagen/ADP and collagen/epinephrine. Twenty four hours after blood collection, both parameters were prolonged pathologically above the upper limit of the reference range. Numbers of circulating platelets, measured in PRP, decreased after four hours, but no longer after twenty four hours. Mean platelet volumes (MPV) and platelet large cell ratios (P-LCR, 12 fL - 40 fL) decreased over time. Immediately after blood collection, no debris or platelet aggregates could be visualized microscopically. After four hours, first debris and very small aggregates occurred. After 24 hours, platelet aggregates and also debris progressively increased. In accordance to this, the CASY system revealed an increase of platelet aggregates (up to 90 mu m diameter)with increasing storage time. The percentage of CD62P positive platelets and PF4 increased significantly with storage time in resting PRP. When soluble ADP was added to stored PRP samples, the number of activatable platelets decreased significantly over storage time. The present study reveals the importance of a consequent standardization in the preparation of WB and PRP. Platelet morphology and function, particularly platelet reactivity to adherent or soluble agonists in their surrounding milieu, changed rapidly outside the vascular system. This knowledge is of crucial interest, particularly in the field of biomaterial development for cardiovascular applications, and may help to define common standards in the in vitro hemocompatibility testing of biomaterials.},
  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{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}
}
@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}
}