TY - JOUR A1 - Balk, Maria A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Quadruple-shape hydrogels JF - Smart materials and structures N2 - 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. KW - shape-memory KW - hydrogels KW - semi-crystalline Y1 - 2019 U6 - https://doi.org/10.1088/1361-665X/ab0e91 SN - 0964-1726 SN - 1361-665X VL - 28 IS - 5 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Balk, Maria A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Hydrolytic Degradation of Actuators Based on Copolymer Networks From Oligo(epsilon-caprolactone) Dimethacrylate and n-Butyl Acrylate JF - MRS advances N2 - 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. Y1 - 2019 U6 - https://doi.org/10.1557/adv.2019.202 SN - 2059-8521 VL - 4 IS - 21 SP - 1193 EP - 1205 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Balk, Maria A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Actuators based on oligo[(epsilon-caprolactone)-co-glycolide] with accelerated hydrolytic degradation JF - MRS advances : a journal of the Materials Research Society (MRS) N2 - 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. KW - actuation KW - shape memory KW - polymer KW - crystalline Y1 - 2020 U6 - https://doi.org/10.1557/adv.2019.447 SN - 2059-8521 VL - 5 IS - 12-13 SP - 655 EP - 666 PB - Cambridge University Press CY - New York, NY ER - TY - JOUR A1 - Balk, Maria A1 - Behl, Marc A1 - Nöchel, Ulrich A1 - Lendlein, Andreas T1 - Enzymatically triggered Jack-in-the-box-like hydrogels JF - ACS applied materials & interfaces / American Chemical Society N2 - 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. KW - enzyme KW - hydrogels KW - stimuli-sensitive materials KW - shape change KW - poly(e-caprolactone) KW - switch KW - microporous Y1 - 2021 U6 - https://doi.org/10.1021/acsami.1c00466 SN - 1944-8244 SN - 1944-8252 VL - 13 IS - 7 SP - 8095 EP - 8101 PB - American Chemical Society CY - Washington, DC ER - TY - GEN A1 - Balk, Maria A1 - Grijpma, Dirk W. A1 - Lendlein, Andreas T1 - Design and processing of advanced functional polymers for medicine T2 - Polymers for advanced technologies Y1 - 2017 U6 - https://doi.org/10.1002/pat.3980 SN - 1042-7147 SN - 1099-1581 VL - 28 SP - 1203 EP - 1205 PB - Wiley CY - Hoboken ER - TY - INPR A1 - Baudis, Stefan A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Smart polymers for biomedical applications T2 - Macromolecular chemistry and physics Y1 - 2014 U6 - https://doi.org/10.1002/macp.201400561 SN - 1022-1352 SN - 1521-3935 VL - 215 IS - 24 SP - 2399 EP - 2402 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Behl, Marc A1 - Balk, Maria A1 - Lützow, Karola A1 - Lendlein, Andreas T1 - Impact of block sequence on the phase morphology of multiblock copolymers obtained by high-throughput robotic synthesis JF - European polymer journal : EPJ N2 - 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. KW - Multiblock copolymers KW - Sequence structure KW - Phase morphology KW - Polymer KW - library KW - Robotic synthesis KW - High-throughput Y1 - 2021 U6 - https://doi.org/10.1016/j.eurpolymj.2020.110207 SN - 0014-3057 SN - 1873-1945 VL - 143 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Behl, Marc A1 - Balk, Maria A1 - Mansfeld, Ulrich A1 - Lendlein, Andreas T1 - Phase morphology of multiblock copolymers differing in sequence of blocks JF - Macromolecular materials and engineering N2 - 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. KW - electron microscopy KW - multiblock copolymers KW - phase morphology KW - polymer KW - libraries KW - sequence structures KW - wide angle x‐ ray scattering Y1 - 2021 U6 - https://doi.org/10.1002/mame.202000672 SN - 1439-2054 VL - 306 IS - 3 PB - Wiley-VCH CY - Weinheim ER - TY - CHAP A1 - Behl, Marc A1 - Kratz, Karl A1 - Nöchel, Ulrich A1 - Sauter, Tilman A1 - Lendlein, Andreas T1 - Polymer networks capable of reversible shape-memory-effects T2 - Abstracts of papers : joint conference / The Chemical Institute of Cananda, CIC, American Chemical Society, ACS Y1 - 2014 SN - 0065-7727 VL - 248 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Behl, Marc A1 - Razzaq, Muhammad Yasar A1 - Mazurek-Budzynska, Magdalena A1 - Lendlein, Andreas T1 - Polyetheresterurethane based porous scaffolds with tailorable architectures by supercritical CO2 foaming JF - MRS advances N2 - 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. Y1 - 2020 U6 - https://doi.org/10.1557/adv.2020.345 SN - 2059-8521 VL - 5 IS - 45 SP - 2317 EP - 2330 PB - Cambridge University Press CY - New York, NY ER - TY - JOUR A1 - Behl, Marc A1 - Zhao, Qian A1 - Lendlein, Andreas T1 - Glucose-responsive shape-memory cryogels JF - Journal of materials research : JMR N2 - 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. KW - shape memory KW - polymer KW - porosity Y1 - 2020 U6 - https://doi.org/10.1557/jmr.2020.204 SN - 0884-2914 SN - 2044-5326 VL - 35 IS - 18 SP - 2396 EP - 2404 PB - Springer CY - Berlin ER - TY - JOUR A1 - Bhaskar, Thanga Bhuvanesh Vijaya A1 - Ma, Nan A1 - Lendlein, Andreas A1 - Roch, Toralf T1 - The interaction of human macrophage subsets with silicone as a biomaterial JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - 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. KW - Biomaterials KW - silicone KW - macrophage subsets KW - cytokines/chemokines Y1 - 2015 U6 - https://doi.org/10.3233/CH-151991 SN - 1386-0291 SN - 1875-8622 VL - 61 IS - 2 SP - 119 EP - 133 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Bhuvanesh, Thanga A1 - Machatschek, Rainhard Gabriel A1 - Lysyakova, Liudmila A1 - Kratz, Karl A1 - Schulz, Burkhard A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Collagen type-IV Langmuir and Langmuir-Schafer layers as model biointerfaces to direct stem cell adhesion JF - Biomedical materials : materials for tissue engineering and regenerative medicine N2 - 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. KW - collagen-IV KW - basement membrane KW - Langmuir-Schafer films KW - stem cell adhesion KW - protein KW - ellipsometry Y1 - 2019 U6 - https://doi.org/10.1088/1748-605X/aaf464 SN - 1748-6041 SN - 1748-605X VL - 14 IS - 2 PB - Inst. of Physics Publ. CY - Bristol ER - TY - JOUR A1 - Bhuvanesh, Thanga A1 - Saretia, Shivam A1 - Roch, Toralf A1 - Schöne, Anne-Christin A1 - Rottke, Falko O. A1 - Kratz, Karl A1 - Wang, Weiwei A1 - Ma, Nan A1 - Schulz, Burkhard A1 - Lendlein, Andreas T1 - Langmuir-Schaefer films of fibronectin as designed biointerfaces for culturing stem cells JF - Polymers for advanced technologies N2 - 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. KW - Langmuir-Schaefer method KW - protein adsorption KW - stem cell adhesion KW - cell culture KW - fibronectin Y1 - 2017 U6 - https://doi.org/10.1002/pat.3910 SN - 1042-7147 SN - 1099-1581 VL - 28 SP - 1305 EP - 1311 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Binzen, Eva A1 - Lendlein, Andreas A1 - Kelch, S. A1 - Rickert, D. A1 - Franke, R. P. T1 - Biomaterial-microvasculature interaction on polymers after implantation in mice Y1 - 2004 ER - TY - JOUR A1 - Blocki, Anna A1 - Löwenberg, Candy A1 - Jiang, Yi A1 - Kratz, Karl A1 - Neffe, Axel T. A1 - Jung, Friedrich A1 - Lendlein, Andreas T1 - Response of encapsulated cells to a gelatin matrix with varied bulk and microenvironmental elastic properties JF - Polymers for advanced technologies N2 - 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. KW - mechanotransduction KW - hydrogel KW - gelatin KW - cell encapsulation KW - matrix elasticity Y1 - 2017 U6 - https://doi.org/10.1002/pat.3947 SN - 1042-7147 SN - 1099-1581 VL - 28 SP - 1245 EP - 1251 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Bochove, Bas van A1 - Grijpma, Dirk W. A1 - Lendlein, Andreas A1 - Seppälä, Jukka T1 - Designing advanced functional polymers for medicine JF - European polymer journal : EPJ Y1 - 2021 U6 - https://doi.org/10.1016/j.eurpolymj.2021.110573 SN - 0014-3057 VL - 155 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Braune, Steffen A1 - Froehlich, G. M. A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Effect of temperature on platelet adherence JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - 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. KW - Biomaterial KW - thrombogenicity KW - platelet adhesion KW - platelet activation KW - temperature Y1 - 2016 U6 - https://doi.org/10.3233/CH-152028 SN - 1386-0291 SN - 1875-8622 VL - 61 SP - 681 EP - 688 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Braune, Steffen A1 - Gross, M. A1 - Walter, M. A1 - Zhou, Shengqiang A1 - Dietze, Siegfried A1 - Rutschow, S. A1 - Lendlein, Andreas A1 - Tschoepe, C. A1 - Jung, Friedrich T1 - Adhesion and activation of platelets from subjects with coronary artery disease and apparently healthy individuals on biomaterials JF - Journal of biomedical materials research : an official journal of the Society for Biomaterials, the Japanese Society for Biomaterials; the Australian Society for Biomaterials N2 - 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. KW - platelets KW - biomaterials KW - hemocompatibility KW - cardiovascular disease KW - cardiovascular implant Y1 - 2016 U6 - https://doi.org/10.1002/jbm.b.33366 SN - 1552-4973 SN - 1552-4981 VL - 104 SP - 210 EP - 217 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Braune, Steffen A1 - Latour, Robert A. A1 - Reinthaler, Markus A1 - Landmesser, Ulf A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - In Vitro Thrombogenicity Testing of Biomaterials JF - Advanced healthcare materials N2 - The short- and long-term thrombogenicity of implant materials is still unpredictable, which is a significant challenge for the treatment of cardiovascular diseases. A knowledge-based approach for implementing biofunctions in materials requires a detailed understanding of the medical device in the biological system. In particular, the interplay between material and blood components/cells as well as standardized and commonly acknowledged in vitro test methods allowing a reproducible categorization of the material thrombogenicity requires further attention. Here, the status of in vitro thrombogenicity testing methods for biomaterials is reviewed, particularly taking in view the preparation of test materials and references, the selection and characterization of donors and blood samples, the prerequisites for reproducible approaches and applied test systems. Recent joint approaches in finding common standards for a reproducible testing are summarized and perspectives for a more disease oriented in vitro thrombogenicity testing are discussed. KW - biomaterials KW - blood tests KW - implants KW - in vitro KW - thrombogenicity Y1 - 2019 U6 - https://doi.org/10.1002/adhm.201900527 SN - 2192-2640 SN - 2192-2659 VL - 8 IS - 21 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Braune, Steffen A1 - Walter, M. A1 - Schulze, F. A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Changes in platelet morphology and function during 24 hours of storage JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - 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. KW - Platelet KW - platelet function KW - platelet rich plasma KW - whole blood KW - platelet aging KW - platelet storage KW - hemocompatibility KW - biomaterials Y1 - 2014 U6 - https://doi.org/10.3233/CH-141876 SN - 1386-0291 SN - 1875-8622 VL - 58 IS - 1 SP - 159 EP - 170 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Brunacci, Nadia A1 - Neffe, Axel T. A1 - Wischke, Christian A1 - Naolou, Toufik A1 - Nöchel, Ulrich A1 - Lendlein, Andreas T1 - Oligodepsipeptide (nano)carriers BT - computational design and analysis of enhanced drug loading JF - Journal of controlled release N2 - 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. KW - Oligodepsipeptide KW - Drug loading KW - Nanoparticles KW - Docking study KW - Molecular interaction design Y1 - 2019 U6 - https://doi.org/10.1016/j.jconrel.2019.03.004 SN - 0168-3659 SN - 1873-4995 VL - 301 SP - 146 EP - 156 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Brunacci, Nadia A1 - Wischke, Christian A1 - Naolou, Toufik A1 - Neffe, Axel T. A1 - Lendlein, Andreas T1 - Influence of surfactants on depsipeptide submicron particle formation JF - European Journal of Pharmaceutics and Biopharmaceutics N2 - 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. KW - Depsipeptide KW - Particle size KW - Surfactants KW - Submicron particles Y1 - 2017 U6 - https://doi.org/10.1016/j.ejpb.2016.11.011 SN - 0939-6411 SN - 1873-3441 VL - 116 SP - 61 EP - 65 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bäckemo, Johan Dag Valentin A1 - Liu, Yue A1 - Lendlein, Andreas T1 - Bio-inspired and computer-supported design of modulated shape changes in polymer materials JF - MRS communications / a publication of the Materials Research Society N2 - 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. KW - Additive manufacturing KW - Biomimetic KW - Shape memory KW - Modelling KW - Polymer Y1 - 2021 U6 - https://doi.org/10.1557/s43579-021-00056-6 SN - 2159-6867 VL - 11 IS - 4 SP - 462 EP - 469 PB - Springer CY - Berlin ER - TY - JOUR A1 - Dal Bianco, Andrea A1 - Wischke, Christian A1 - Zhou, Shuo A1 - Lendlein, Andreas T1 - Controlling surface properties and permeability of polyglycerol network films JF - Polymers for advanced technologies N2 - While branched polyglycerol (PG)-based molecules are well established as hydrophilic particles, the capacity of utilizing PG in bulk materials and opportunities arising by their further surface functionalization have only recently been considered. Here we investigated how the mold used in PG network synthesis may affect surface composition and how the permeability of substances through PG can be controlled by altering network structure, i.e. introducing 20mol% oligoethylene glycol (OEG) bifunctional spacer molecules. Overall, PG-based bulk network materials were shown to be tailorable, hydrophilic, low swelling and relatively stiff polyether-based materials, with low impact of salt onto material properties. Based on these features, but also on the principal capacity of free hydroxyl groups to be used for functionalization reactions, these materials may be an interesting platform for medical and technical applications, e.g. as diffusion-rate controlling membrane in aqueous environment. Copyright (c) 2016 John Wiley & Sons, Ltd. KW - polyglycerol KW - surface properties KW - diffusion KW - network structure Y1 - 2017 U6 - https://doi.org/10.1002/pat.3917 SN - 1042-7147 SN - 1099-1581 VL - 28 SP - 1263 EP - 1268 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Deng, Zijun A1 - Wang, Weiwei A1 - Xu, Xun A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Modulation of mesenchymal stem cell migration using programmable polymer sheet actuators JF - MRS advances N2 - 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. Y1 - 2020 U6 - https://doi.org/10.1557/adv.2020.235 SN - 2059-8521 VL - 5 IS - 46-47 SP - 2381 EP - 2390 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Deng, Zijun A1 - Wang, Weiwei A1 - Xu, Xun A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Polydopamine-based biofunctional substrate coating promotes mesenchymal stem cell migration JF - MRS advances : a journal of the Materials Research Society (MRS) N2 - 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. Y1 - 2021 U6 - https://doi.org/10.1557/s43580-021-00091-4 SN - 2059-8521 VL - 6 IS - 31 SP - 739 EP - 744 PB - Springer Nature Switzerland AG CY - Cham ER - TY - JOUR A1 - Deng, Zijun A1 - Wang, Weiwei A1 - Xua, Xun A1 - Gould, Oliver E. C. A1 - Kratz, Karl A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Polymeric sheet actuators with programmable bioinstructivity JF - PNAS N2 - 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. KW - reversible shape-memory actuator KW - mesenchymal stem cells KW - calcium influx KW - HDAC1 KW - RUNX2 Y1 - 2020 U6 - https://doi.org/10.1073/pnas.1910668117 SN - 1091-6490 VL - 117 IS - 4 SP - 1895 EP - 1901 PB - National Academy of Sciences CY - Washington, DC ER - TY - GEN A1 - Deng, Zijun A1 - Wang, Weiwei A1 - Xua, Xun A1 - Gould, Oliver E. C. A1 - Kratz, Karl A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Polymeric sheet actuators with programmable bioinstructivity T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1441 KW - reversible shape-memory actuator KW - mesenchymal stem cells KW - calcium influx KW - HDAC1 KW - RUNX2 Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-515490 SN - 1866-8372 IS - 4 ER - TY - JOUR A1 - Deng, Zijun A1 - Zou, Jie A1 - Wang, Weiwei A1 - Nie, Yan A1 - Tung, Wing-Tai A1 - Ma, Nan A1 - Lendlein, Andreas T1 - Dedifferentiation of mature adipocytes with periodic exposure to cold JF - Clinical hemorheology and microcirculation : blood flow and vessels N2 - 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. KW - Adipocyte KW - dedifferentiation KW - cold KW - lipid Y1 - 2019 U6 - https://doi.org/10.3233/CH-199005 SN - 1386-0291 SN - 1875-8622 VL - 71 IS - 4 SP - 415 EP - 424 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Fang, Liang A1 - Gould, Oliver E. C. A1 - Lysyakova, Liudmila A1 - Jiang, Yi A1 - Sauter, Tilman A1 - Frank, Oliver A1 - Becker, Tino A1 - Schossig, Michael A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Implementing and quantifying the shape-memory effect of single polymeric micro/nanowires with an atomic force microscope JF - ChemPhysChem : a European journal of chemical physics and physical chemistry N2 - 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. KW - cyclic thermomechanical testing KW - atomic force microscopy KW - soft matter micro- and nanowires KW - shape-memory effect KW - materials science Y1 - 2018 U6 - https://doi.org/10.1002/cphc.201701362 SN - 1439-4235 SN - 1439-7641 VL - 19 IS - 16 SP - 2078 EP - 2084 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Fang, Liang A1 - Yan, Wan A1 - Nöchel, Ulrich A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Programming structural functions in phase-segregated polymers by implementing a defined thermomechanical history JF - Polymer : the international journal for the science and technology of polymers N2 - Unwanted shrinkage behaviors or failure in structural functions such as mechanical strength or deformability of polymeric products related to their thermomechanical history are a major challenge in production of plastics. Here, we address the question whether we can turn this challenge into an opportunity by creating defined thermomechanical histories in polymers, represented by a specific morphology and nanostructure, to equip polymeric shaped bodies with desired functions, e.g. a temperature-memory, by hot, warm or cold deformation into multiblock copolymers having two partially overlapping melting transitions. A copolyesterurethane named PDLCL, consisting of poly(epsilon-caprolactone) (PCL) and poly(omega-pentadecalactone) (PPDL) crystalline domains, exhibiting a pronounced phase-segregated morphology and partially overlapping melting transitions was selected for this study. Different types of PCL and PPDL crystals as well as distinct degrees of orientation in both amorphous and crystalline domains were obtained after deformation at 20 or 40 degrees C and to a lower extent at 60 degrees C. The generated non-isotropic structures were stable at ambient temperature and represent the different stresses stored. Stress-free heating experiments showed that the relaxation in both amorphous and crystalline phases occurred predominantly with melting of PCL crystals. When the switching temperature, which was similar to the applied deformation temperature (temperature-memory), was exceeded in stress-free heating experiments, the implemented thermomechanical history could be reversed. In contrast, during constant-strain heating to 60 degrees C the generated structural features remained almost unchanged. These findings provide insights about the structure function relation in multiblock copolymers with two crystalline phases exhibiting a temperature-memory effect by implementation of specific thermomechanical histories, which might be a general principle for tailoring other functions like mechanical strength or deformability in polymers. (C) 2016 Elsevier Ltd. All rights reserved. KW - Temperature-memory effect KW - Phase morphology KW - Thermomechanical history Y1 - 2016 U6 - https://doi.org/10.1016/j.polymer.2016.08.105 SN - 0032-3861 SN - 1873-2291 VL - 102 SP - 54 EP - 62 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Farhan, Muhammad A1 - Behl, Marc A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Origami hand for soft robotics driven by thermally controlled polymeric fiber actuators JF - MRS communications / a publication of the Materials Research Society N2 - 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. KW - Robotics KW - Polymer KW - Fiber KW - Actuation KW - Shape-memory Y1 - 2021 U6 - https://doi.org/10.1557/s43579-021-00058-4 SN - 2159-6859 SN - 2159-6867 VL - 11 IS - 4 SP - 476 EP - 482 PB - Springer CY - Berlin ER - TY - JOUR A1 - Farhan, Muhammad A1 - Chaudhary, Deeptangshu A1 - Nöchel, Ulrich A1 - Behl, Marc A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Electrical actuation of coated and composite fibers based on poly[ethylene-co-(vinyl acetate)] JF - Macromolecular materials and engineering N2 - 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. KW - artificial muscles KW - fiber actuators KW - resistive heating KW - shape‐memory polymer actuators KW - soft robotics Y1 - 2020 U6 - https://doi.org/10.1002/mame.202000579 SN - 1438-7492 SN - 1439-2054 VL - 306 IS - 2 PB - Wiley-VCH CY - Weinheim ER - TY - GEN A1 - Farhan, Muhammad A1 - Chaudhary, Deeptangshu A1 - Nöchel, Ulrich A1 - Behl, Marc A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Electrical actuation of coated and composite fibers based on poly[ethylene-co-(vinyl acetate)] T2 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1375 KW - artificial muscles KW - fiber actuators KW - resistive heating KW - shape‐memory polymer actuators KW - soft robotics Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-571679 SN - 1866-8372 IS - 2 ER - TY - JOUR A1 - Farhan, Muhammad A1 - Rudolph, Tobias A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Torsional Fiber Actuators from Shape-memory Polymer JF - MRS Advances N2 - Humanoid robots, prosthetic limbs and exoskeletons require soft actuators to perform their primary function, which is controlled movement. In this wont we explored whether crosslinked poly[ethylene-co-(vinyl acetate)] (cPEVA) fibers, with different vinyl acetate (VA) content can serve as torsional fiber actuators. exhibiting temperature controlled reversible rotational changes. Broad melting transitions ranging from 50 to 90 degrees C for cPEVA18-165 or from 40 to 80 degrees C for cPEVA28-165 fibers in combination with complete crystallization at temperatures around 10 degrees C make them suitable actuating materials with adjustable actuation temperature ranges between 10 and 70 degrees C during repetitive cooling and heating. The obtained fibers exhibited a circular cross section with diameters around 0.4 +/- 0.1 mm, while a length of 4 cm was employed for the investigation of reversible rotational actuation after programming by twist insertion using 30 complete rotations at a temperature above melting transition. Repetitive heating and cooling between 10 to 60 degrees C or 70 degrees C of one-end-tethered programmed fibers revealed reversible rotations and torsional force. During cooling 3 +/- 1 complete rotations (Delta theta(r) = + 1080 +/- 360 degrees) in twisting direction were observed, while 4 +/- 1 turns in the opposite direction (Delta theta(r) = - 1440 +/- 1360 degrees) were found during heating. Such torsional fiber actuators, which are capable of approximately one rotation per cm fiber length, can serve as miniaturized rotary motors to provide rotational actuation in futuristic humanoid robots. Y1 - 2018 U6 - https://doi.org/10.1557/adv.2018.621 SN - 2059-8521 VL - 3 IS - 63 SP - 3861 EP - 3868 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Farhan, Muhammad A1 - Rudolph, Tobias A1 - Nöchel, Ulrich A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Extractable Free Polymer Chains Enhance Actuation Performance of Crystallizable Poly(epsilon-caprolactone) Networks and Enable Self-Healing JF - Polymers N2 - 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. KW - shape-memory polymer actuators KW - soft actuators KW - self-healing KW - poly(epsilon-caprolactone) KW - thermoplastics Y1 - 2018 U6 - https://doi.org/10.3390/polym10030255 SN - 2073-4360 VL - 10 IS - 3 PB - MDPI CY - Basel ER - TY - JOUR A1 - Farhan, Muhammad A1 - Rudolph, Tobias A1 - Nöchel, Ulrich A1 - Yan, Wan A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Noncontinuously Responding Polymeric Actuators JF - ACS applied materials & interfaces N2 - Reversible movements of current polymeric actuators stem from the continuous response to signals from a controlling unit, and subsequently cannot be interrupted without stopping or eliminating the input trigger. Here, we present actuators based on cross-linked blends of two crystallizable polymers capable of pausing their movements in a defined manner upon continuous cyclic heating and cooling. This noncontinuous actuation can be adjusted by varying the applied heating and cooling rates. The feasibility of these devices for technological applications was shown in a 140 cycle experiment of free-standing noncontinuous shape shifts, as well as by various demonstrators. KW - soft robotics KW - polymer actuators KW - thermo-sensitivity KW - shape shifting materials KW - crystallization behavior Y1 - 2017 U6 - https://doi.org/10.1021/acsami.7b11316 SN - 1944-8244 VL - 9 SP - 33559 EP - 33564 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Federico, Stefania A1 - Nöchel, Ulrich A1 - Löwenberg, Candy A1 - Lendlein, Andreas A1 - Neffe, Axel T. T1 - Supramolecular hydrogel networks formed by molecular recognition of collagen and a peptide grafted to hyaluronic acid JF - Acta biomaterialia N2 - The extracellular matrix (ECM) is a nano-structured, highly complex hydrogel, in which the macromolecules are organized primarily by non-covalent interactions. Here, in a biomimetic approach, the decorin-derived collagen-binding peptide LSELRLHNN was grafted to hyaluronic acid (HA) in order to enable the formation of a supramolecular hydrogel network together with collagen. The storage modulus of a mixture of collagen and HA was increased by more than one order of magnitude (G′ = 157 Pa) in the presence of the HA-grafted peptide compared to a mixture of collagen and HA (G′ = 6 Pa). The collagen fibril diameter was decreased, as quantified using electron microscopy, in the presence of the HA-grafted peptide. Here, the peptide mimicked the function of decorin by spatially organizing collagen. The advantage of this approach is that the non-covalent crosslinks between collagen molecules and the HA chains created by the peptide form a reversible and dynamic hydrogel, which could be employed for a diverse range of applications in regenerative medicine. Statement of Significance Biopolymers of the extracellular matrix (ECM) like collagen or hyaluronan are attractive starting materials for biomaterials. While in biomaterial science covalent crosslinking is often employed, in the native ECM, stabilization and macromolecular organization is primarily based on non-covalent interactions, which allows dynamic changes of the materials. Here, we show that collagen-binding peptides, derived from the small proteoglycan decorin, grafted to hyaluronic acid enable supramolecular stabilization of collagen hydrogels. These hydrogels have storage moduli more than one order of magnitude higher than mixtures of collagen and hyaluronic acid. Furthermore, the peptide supported the structural organization of collagen. Such hydrogels could be employed for a diverse range of applications in regenerative medicine. Furthermore, the rational design helps in the understanding ECM structuring. KW - Biopolymers KW - Collagen-binding peptide KW - Hyaluronic acid KW - Hydrogels KW - Mechanical properties Y1 - 2016 U6 - https://doi.org/10.1016/j.actbio.2016.04.018 SN - 1742-7061 SN - 1878-7568 VL - 38 SP - 1 EP - 10 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Federico, Stefania A1 - Pierce, Benjamin F. A1 - Piluso, Susanna A1 - Wischke, Christian A1 - Lendlein, Andreas A1 - Neffe, Axel T. T1 - Design of Decorin-Based Peptides That Bind to CollagenI and their Potential as Adhesion Moieties in Biomaterials JF - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition N2 - Mimicking the binding epitopes of protein-protein interactions by using small peptides is important for generating modular biomimetic systems. A strategy is described for the design of such bioactive peptides without accessible structural data for the targeted interaction, and the effect of incorporating such adhesion peptides in complex biomaterial systems is demonstrated. The highly repetitive structure of decorin was analyzed to identify peptides that are representative of the inner and outer surface, and it was shown that only peptides based on the inner surface of decorin bind to collagen. The peptide with the highest binding affinity for collagenI, LHERHLNNN, served to slow down the diffusion of a conjugated dye in a collagen gel, while its dimer could physically crosslink collagen, thereby enhancing the elastic modulus of the gel by one order of magnitude. These results show the potential of the identified peptides for the design of biomaterials for applications in regenerative medicine. KW - biomaterials KW - collagen KW - gels KW - peptides KW - protein-protein interactions Y1 - 2015 U6 - https://doi.org/10.1002/anie.201505227 SN - 1433-7851 SN - 1521-3773 VL - 54 IS - 37 SP - 10980 EP - 10984 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Folikumah, Makafui Y. A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Reaction behaviour of peptide-based single thiol-thioesters exchange reaction substrate in the presence of externally added thiols JF - MRS communications / a publication of the Materials Research Society N2 - 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. KW - Biomaterials KW - Biomimetic KW - Mass spectrometry KW - Nuclear magnetic resonance KW - (NMR) Y1 - 2021 U6 - https://doi.org/10.1557/s43579-021-00041-z SN - 2159-6859 SN - 2159-6867 VL - 11 IS - 4 SP - 402 EP - 410 PB - Springer CY - Berlin ER - TY - JOUR A1 - Folikumah, Makafui Yao A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Thiol-Thioester exchange reactions in precursors enable pH-triggered hydrogel formation JF - Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences N2 - 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. Y1 - 2021 U6 - https://doi.org/10.1021/acs.biomac.0c01690 SN - 1525-7797 SN - 1526-4602 VL - 22 IS - 5 SP - 1875 EP - 1884 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Folikumah, Makafui Yao A1 - Neffe, Axel T. A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Thiol Michael-Type reactions of optically active mercapto-acids in aqueous medium JF - MRS advances : a journal of the Materials Research Society N2 - 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. KW - biomaterial KW - biomedical KW - biomimetic (chemical reaction) KW - chemical synthesis Y1 - 2019 U6 - https://doi.org/10.1557/adv.2019.308 SN - 2059-8521 VL - 4 IS - 46-47 SP - 2515 EP - 2525 PB - Springer Nature Switzerland AG CY - Cham ER - TY - JOUR A1 - Friess, Fabian A1 - Lendlein, Andreas A1 - Wischke, Christian T1 - Photoinduced synthesis of polyester networks from methacrylate functionalized precursors: analysis of side reactions JF - Polymers for advanced technologies N2 - Polyester networks can be prepared by ultraviolet (UV)-light-induced radical polymerization of methacrylate functionalized oligo(epsilon-caprolactone)s. The properties and functions of the obtained materials depend on defined network structures and may be altered, if crosslinking would occur by side reactions in other positions than the methacrylate endgroups. In order to explore whether and to which extent such side reactions occur, network synthesis as well as related model reactions were performed in the absence of photoinitiator. Hereby precursor structures (linear and four-arm star-shaped) and reaction conditions (in solution and in the melt) were varied. Unspecific side reactions were found only upon extensive UV irradiation for 60min (26 mW cm(-2)) with minor but detectable alterations of physicochemical properties of the networks. The analysis of model reactions suggested minor photolytic cleavage of ester bonds during polymer network synthesis. However, the effect of these side reactions on network properties and functions appeared to be less relevant than an incomplete precursor integration because of a too short UV irradiation for crosslinking. Copyright (c) 2014 John Wiley & Sons, Ltd. KW - poly(epsilon-caprolactone) methacrylate KW - crosslinking KW - excimer UV light KW - side reaction KW - photoinduced radical polymerization Y1 - 2014 U6 - https://doi.org/10.1002/pat.3313 SN - 1042-7147 SN - 1099-1581 VL - 25 IS - 11 SP - 1285 EP - 1292 PB - Wiley-Blackwell CY - Hoboken ER - TY - CHAP A1 - Friess, Fabian A1 - Lendlein, Andreas A1 - Wischke, Christian T1 - Investigating side-reactions during UV-induced preparation of oligo(epsilon-caprolactone) based shape-memory polymer networks T2 - Abstracts of papers : joint conference / The Chemical Institute of Cananda, CIC, American Chemical Society, ACS Y1 - 2013 SN - 0065-7727 VL - 245 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Friess, Fabian A1 - Lendlein, Andreas A1 - Wischke, Christian T1 - Size control of shape switchable micronetworks by fast two-step microfluidic templating JF - Journal of materials research N2 - 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. Y1 - 2021 U6 - https://doi.org/10.1557/s43578-021-00295-2 SN - 0884-2914 SN - 2044-5326 VL - 36 IS - 16 SP - 3248 EP - 3257 PB - Springer CY - Berlin ER - TY - JOUR A1 - Friess, Fabian A1 - Roch, Toralf A1 - Seifert, Barbara A1 - Lendlein, Andreas A1 - Wischke, Christian T1 - Phagocytosis of spherical and ellipsoidal micronetwork colloids from crosslinked poly(epsilon-caprolactone) JF - International Journal of Pharmaceutics N2 - The effect of non-spherical particle shapes on cellular uptake has been reported as a general design parameter to control cellular recognition of particulate drug carriers. Beside shape, also size and cell-particle ratio should mutually effect phagocytosis. Here, the capability to control cellular uptake of poly(epsilon-caprolactone) (PCL) based polymer micronetwork colloids (MNC), a carrier system that can be transferred to various shapes, is explored in vitro at test conditions allowing multiple cell-particle contacts. PCL-based MNC were synthesized as spheres with a diameter of similar to 6, similar to 10, and 13 mu m, loaded with a fluorescent dye by a specific technique of swelling, redispersion and drying, and transferred into different ellipsoidal shapes by a phantom stretching method. The boundaries of MNC deformability to prolate ellipsoid target shapes were systematically analyzed and found to be at an aspect ratio AR of similar to 4 as obtained by a phantom elongation epsilon(ph) of similar to 150%. Uptake studies with a murine macrophages cell line showed shape dependency of phagocytosis for selected conditions when varying particle sizes (similar to 6 and 10 mu m),and shapes (epsilon(ph): 0, 75 or 150%), cell-particle ratios (1:1, 1:2, 1:10, 1:50), and time points (1-24 h). For larger-sized MNC, there was no significant shape effect on phagocytosis as these particles may associate with more than one cell, thus increasing the possibility of phagocytosis by any of these cells. Accordingly, controlling shape effects on phagocytosis for carriers made from degradable polymers relevant for medical applications requires considering further parameters besides shape, such as kinetic aspects of the exposure and uptake by cells. KW - Particle shape KW - Phagocytosis KW - Macrophage KW - Polymer micronetwork colloids KW - Poly(epsilon-caprolactone) Y1 - 2019 U6 - https://doi.org/10.1016/j.ijpharm.2019.118461 SN - 0378-5173 SN - 1873-3476 VL - 567 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Friess, Fabian A1 - Wischke, Christian A1 - Behl, Marc A1 - Lendlein, Andreas T1 - Oligo(epsilon-caprolactone)-based polymer networks prepared by photocrosslinking in solution JF - Journal of applied biomaterials & functional materials N2 - Purpose: Polymer networks with adjustable properties prepared from endgroup-functionalized oligoesters by UV-crosslinking in melt have evolved into versatile multifunctional biomaterials. In addition to the molecular weight or architecture of precursors, the reaction conditions for crosslinking are pivotal for the polymer network properties. Crosslinking of precursors in solution may facilitate low-temperature processes and are compared here to networks synthesized in melt. Methods: Oligo(epsilon-caprolactone)-(z) methacrylate (oCL-(z) IEMA) precursors with a linear (z = di) or a four-armed star-shaped (z = tetra) architecture were crosslinked by radical polymerization in melt or in solution with UV irradiation. The thermal, mechanical, and swelling properties of the polymer networks obtained were characterized. Results: Crosslinking in solution resulted in materials with lower Young's moduli (E), lower maximum stress (sigma(max)), and higher elongation at break (epsilon(B)) as determined at 70 degrees C. Polymer networks from 8 kDa star-shaped precursors exhibited poor elasticity when synthesized in the melt, but can be established as stretchable materials with a semi-crystalline morphology, a high gel-content, and a high elongation at break when prepared in solution. Conclusions: The crosslinking condition of methacrylate functionalized precursors significantly affected network properties. For some types of precursors such as star-shaped telechelics, synthesis in solution provided semi-crystalline elastic materials that were not accessible from crosslinking in melt. KW - Crosslinking KW - Methacrylate KW - Multifunctional polyester networks KW - Poly(epsilon-caprolactone) KW - Polymer network properties Y1 - 2012 U6 - https://doi.org/10.5301/JABFM.2012.10372 SN - 2280-8000 VL - 10 IS - 3 SP - 273 EP - 279 PB - Wichtig CY - Milano ER - TY - JOUR A1 - Friess, Fabian A1 - Wischke, Christian A1 - Lendlein, Andreas T1 - Microscopic analysis of shape-shiftable oligo(epsilon-caprolactone)-based particles JF - MRS advances N2 - 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. KW - biomaterial KW - particulate KW - shape memory KW - responsive Y1 - 2019 U6 - https://doi.org/10.1557/adv.2019.392 SN - 2059-8521 VL - 4 IS - 59-60 SP - 3199 EP - 3206 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Frieß, Fabian A1 - Lendlein, Andreas A1 - Wischke, Christian T1 - Switching microobjects from low to high aspect ratios using a shape-memory effect JF - Soft matter N2 - 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. Y1 - 2021 U6 - https://doi.org/10.1039/d1sm00947h SN - 1744-6848 VL - 17 IS - 41 SP - 9326 EP - 9331 PB - Royal Society of Chemistry CY - London ER -