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 - JOUR A1 - Izraylit, Victor A1 - Gould, Oliver E. C. A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Investigating the phase-morphology of PLLA-PCL multiblock copolymer/PDLA blends cross-linked using stereocomplexation JF - MRS advances N2 - The macroscale function of multicomponent polymeric materials is dependent on their phase-morphology. Here, we investigate the morphological structure of a multiblock copolymer consisting of poly(L-lactide) and poly(epsilon-caprolactone) segments (PLLA-PCL), physically cross-linked by stereocomplexation with a low molecular weight poly(D-lactide) oligomer (PDLA). The effects of blend composition and PLLA-PCL molecular structure on the morphology are elucidated by AFM, TEM and SAXS. We identify the formation of a lattice pattern, composed of PLA domains within a PCL matrix, with an average domain spacing d0 = 12 - 19 nm. The size of the PLA domains were found to be proportional to the block length of the PCL segment of the copolymer and inversely proportional to the PDLA content of the blend. Changing the PLLA-PCL / PDLA ratio caused a shift in the melt transition Tm attributed to the PLA stereocomplex crystallites, indicating partial amorphous phase dilution of the PLA and PCL components within the semicrystalline material. By elucidating the phase structure and thermal character of multifunctional PLLA-PCL / PDLA blends, we illustrate how composition affects the internal structure and thermal properties of multicomponent polymeric materials. This study should facilitate the more effective incorporation of a variety of polymeric structural units capable of stimuli responsive phase transitions, where an understanding the phase-morphology of each component will enable the production of multifunctional soft-actuators with enhanced performance. KW - polymer KW - blend KW - nanostructure KW - morphology Y1 - 2020 U6 - https://doi.org/10.1557/adv.2019.465 SN - 2059-8521 VL - 5 IS - 14-15 SP - 699 EP - 707 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Izraylit, Victor A1 - Hommes-Schattmann, Paul J. A1 - Neffe, Axel T. A1 - Gould, Oliver E. C. A1 - Lendlein, Andreas T1 - Polyester urethane functionalizable through maleimide side-chains and cross-linkable by polylactide stereocomplexes JF - European polymer journal N2 - Sustainable multifunctional alternatives to fossil-derived materials, which can be functionalized and are degradable, can be envisioned by combining naturally derived starting materials with an established polymer design concept. Modularity and chemical flexibility of polyester urethanes (PEU) enable the combination of segments bearing functionalizable moieties and the tailoring of the mechanical and thermal properties. In this work, a PEU multiblock structure was synthesized from naturally derived L-lysine diisocyanate ethyl ester (LDI), poly(L-lactide) diol (PLLA) and N-(2,3-dihydroxypropyl)-maleimide (MID) in a one-step reaction. A maleimide side-chain (MID) provided a reactive site for the catalyst-free coupling of thiols shown for L-cysteine with a yield of 94%. Physical cross-links were generated by blending the PEU with poly(D-lactide) (PDLA), upon which the PLLA segments of the PEU and the PDLA formed stereocomplexes. Stereocomplexation occurred spontaneously during solution casting and was investigated with WAXS and DSC. Stereocomplex crystallites were observed in the blends, while isotactic PLA crystallization was not observed. The presented material platform with tailorable mechanical properties by blending is of specific interest for engineering biointerfaces of implants or carrier systems for bioactive molecules. KW - Functionalization KW - Polylactide stereocomplex KW - Biomolecules coupling Y1 - 2020 U6 - https://doi.org/10.1016/j.eurpolymj.2020.109916 SN - 0014-3057 SN - 1873-1945 VL - 137 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Izraylit, Victor A1 - Hommes-Schattmann, Paul Jacob A1 - Neffe, Axel T. A1 - Gould, Oliver E. C. A1 - Lendlein, Andreas T1 - Alkynyl-functionalized chain-extended PCL for coupling to biological molecules JF - European polymer journal N2 - Chemical functionalization of poly(epsilon-caprolactone) (PCL) enables a molecular integration of additional function. Here, we report an approach to incorporate reactive alkynyl side-groups by synthesizing a chain-extended PCL, where the reactive site is introduced through the covalently functionalizable chain extender 3 (prop-2-yn-1-yloxy)propane-1,2-diol (YPD). Chain-extended PCL with M-w of 101 to 385 kg.mol(-1) were successfully synthesized in a one-pot reaction from PCL-diols with various molar masses, L-lysine ethyl ester diisocyanate (LDI) or trimethyl(hexamethylene)diisocyanate (TMDI), and YPD, in which the density of functionalizable groups and spacing between them can be controlled by the composition of the polymer. The employed diisocyanate compounds and YPD possess an asymmetric structure and form a non-crystallizable segment leaving the PCL crystallites to dominate the material's mechanical properties. The mixed glass transition temperature T-g = - 60 to - 46 degrees C of the PCL/polyurethane amorphous phase maintains the synthesized materials in a highly elastic state at ambient and physiological conditions. Reaction conditions for covalent attachment in copper(I)-catalyzed azide-alkyne-cycloaddition reactions (CuAAC) in solution were optimized in a series of model reactions between the alkyne moieties of the chain-extended PCL and benzyl azide, reaching conversions over 95% of the alkyne moieties and with yields of up to 94% for the purified functionalized PCL. This methodology was applied for reaction with the azide-functionalized cell adhesion peptide GRGDS. The required modification of the peptide provides selectivity in the coupling reactions. The obtained results suggest that YPD could potentially be employed as versatile molecular unit for the creation of a variety of functionalizable polyesters as well as polyurethanes and polycarbonates offering efficient and selective click-reactions. KW - copper-catalyzed alkyne-azide cycloaddition KW - chain-extended KW - polycaprolactone KW - RGD-peptide KW - side-chains functionalization Y1 - 2020 U6 - https://doi.org/10.1016/j.eurpolymj.2020.109908 SN - 0014-3057 SN - 1873-1945 VL - 136 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Liu, Yue A1 - Gould, Oliver E. C. A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Shape-memory actuation of individual micro-/nanofibers JF - MRS Advances N2 - Advances in the fabrication and characterization of polymeric nanomaterials has greatly advanced the miniaturization of soft actuators, creating materials capable of replicating the functional physical behavior previously limited to the macroscale. Here, we demonstrate how a reversible shape-memory polymer actuation can be generated in a single micro/nano object, where the shape change during actuation of an individual fiber can be dictated by programming using an AFM-based method. Electrospinning was used to prepare poly(epsilon-caprolactone) micro-/nanofibers, which were fixed and crosslinked on a structured silicon wafer. The programming as well as the observation of recovery and reversible displacement of the fiber were performed by vertical three point bending, using an AFM testing platform introduced here. A plateau tip was utilized to improve the stability of the fiber contact and working distance, enabling larger deformations and greater rbSMPA performance. Values for the reversible elongation of epsilon(rev)= 3.4 +/- 0.1% and 10.5 +/- 0.1% were obtained for a single micro (d = 1.0 +/- 0.2 mu m) and nanofiber (d = 300 +/- 100 nm) in cyclic testing between the temperatures 10 and 60 degrees C. The reversible actuation of the nanofiber was successfully characterized for 10 cycles. The demonstration and characterization of individual shape-memory nano and microfiber actuators represents an important step in the creation of miniaturized robotic devices capable of performing complex physical functions at the length scale of cells and structural component of the extracellular matrix. Y1 - 2020 U6 - https://doi.org/10.1557/adv.2020.276 SN - 2059-8521 VL - 5 IS - 46-47 SP - 2391 EP - 2399 PB - Cambridge Univ. Press CY - New York ER - TY - JOUR A1 - Liu, Yue A1 - Gould, Oliver E. C. A1 - Rudolph, Tobias A1 - Fang, Liang A1 - Kratz, Karl A1 - Lendlein, Andreas T1 - Polymeric microcuboids programmable for temperature-memory JF - Macromolecular materials and engineering N2 - Microobjects with programmable mechanical functionality are highly desirable for the creation of flexible electronics, sensors, and microfluidic systems, where fabrication/programming and quantification methods are required to fully control and implement dynamic physical behavior. Here, programmable microcuboids with defined geometries are prepared by a template-based method from crosslinked poly[ethylene-co-(vinyl acetate)] elastomers. These microobjects could be programmed to exhibit a temperature-memory effect or a shape-memory polymer actuation capability. Switching temperaturesT(sw)during shape recovery of 55 +/- 2, 68 +/- 2, 80 +/- 2, and 86 +/- 2 degrees C are achieved by tuning programming temperatures to 55, 70, 85, and 100 degrees C, respectively. Actuation is achieved with a reversible strain of 2.9 +/- 0.2% to 6.7 +/- 0.1%, whereby greater compression ratios and higher separation temperatures induce a more pronounced actuation. Micro-geometry change is quantified using optical microscopy and atomic force microscopy. The realization and quantification of microparticles, capable of a tunable temperature responsive shape-change or reversible actuation, represent a key development in the creation of soft microscale devices for drug delivery or microrobotics. KW - actuation KW - atomic force microscopy KW - biomaterials KW - microparticles KW - shape-memory polymers Y1 - 2020 U6 - https://doi.org/10.1002/mame.202000333 SN - 1438-7492 SN - 1439-2054 VL - 305 IS - 10 PB - Wiley-VCH CY - Weinheim ER -