@article{NaolouLendleinNeffe2019,
  author    = {Naolou, Toufik and Lendlein, Andreas and Neffe, Axel T.},
  title     = {Amides as non-polymerizable catalytic adjuncts enable the ring-opening polymerization of lactide with ferrous acetate under mild conditions},
  series = {Frontiers in Chemistry},
  volume    = {7},
  journal   = {Frontiers in Chemistry},
  publisher = {Frontiers Research Foundation},
  address   = {Lausanne},
  issn      = {2296-2646},
  doi       = {10.3389/fchem.2019.00346},
  pages     = {12},
  year      = {2019},
  abstract  = {Sn-based catalysts are effective in the ring-opening polymerization (ROP) but are toxic. Fe(OAc)(2) used as an alternative catalyst is suitable for the ROP of lactide only at higher temperatures (>170 degrees C), associated with racemization. In the ROP of ester and amide group containing morpholinediones with Fe(OAc)(2) to polydepsipeptides at 135 degrees C, ester bonds were selectively opened. Here, it was hypothesized that ROP of lactones is possible with Fe(OAc)(2) when amides are present in the reactions mixture as Fe-ligands could increase the solubility and activity of the metal catalytic center. The ROP of lactide in the melt with Fe(OAc)(2) is possible at temperatures as low as 105 degrees C, in the presence of N-ethylacetamide or N-rnethylbenzamide as non-polymerizable catalytic adjuncts (NPCA), with high conversion (up to 99 mol\%) and yield (up to 88 mol\%). Polydispersities of polylactide decreased with decreasing reaction temperature to <= 1.1. NMR as well as polarimetric studies showed that no racemization occurred at reaction temperatures <= 145 degrees C. A kinetic study demonstrated a living chain-growth mechanism. MALDI analysis revealed that no side reactions (e.g., cyclization) occurred, though transesterification took place.},
  language  = {en}
}
@article{LendleinBalkTarazonaetal.2019,
  author    = {Lendlein, Andreas and Balk, Maria and Tarazona, Natalia A. and Gould, Oliver E. C.},
  title     = {Bioperspectives for Shape-Memory Polymers as Shape Programmable, Active Materials},
  series = {Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences},
  volume    = {20},
  journal   = {Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences},
  number    = {10},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {1525-7797},
  doi       = {10.1021/acs.biomac.9b01074},
  pages     = {3627 -- 3640},
  year      = {2019},
  abstract  = {Within the natural world, organisms use information stored in their material structure to generate a physical response to a wide variety of environmental changes. The ability to program synthetic materials to intrinsically respond to environmental changes in a similar manner has the potential to revolutionize material science. By designing polymeric devices capable of responsively changing shape or behavior based on information encoded into their structure, we can create functional physical behavior, including a shape memory and an actuation capability. Here we highlight the stimuli-responsiveness and shape-changing ability of biological materials and biopolymer-based materials, plus their potential biomedical application, providing a bioperspective on shape-memory materials. We address strategies to incorporate a shape memory (actuation) function in polymeric materials, conceptualized in terms of its relationship with inputs (environmental stimuli) and outputs (shape change). Challenges and opportunities associated with the integration of several functions in a single material body to achieve multifunctionality are discussed. Finally, we describe how elements that sense, convert, and transmit stimuli have been used to create multisensitive materials.},
  language  = {en}
}
@article{HauserWodtkeTonderaetal.2019,
  author    = {Hauser, Sandra and Wodtke, Robert and Tondera, Christoph and Wodtke, Johanna and Neffe, Axel T. and Hampe, Jochen and Lendlein, Andreas and L{\"o}ser, Reik and Pietzsch, Jens},
  title     = {Characterization of Tissue Transglutaminase as a Potential Biomarker for Tissue Response toward Biomaterials},
  series = {ACS biomaterials science \& engineering},
  volume    = {5},
  journal   = {ACS biomaterials science \& engineering},
  number    = {11},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {2373-9878},
  doi       = {10.1021/acsbiomaterials.9b01299},
  pages     = {5979 -- 5989},
  year      = {2019},
  abstract  = {Tissue transglutaminase (TGase 2) is proposed to be important for biomaterial-tissue interactions due to its presence and versatile functions in the extracellular environment. TGase 2 catalyzes the cross-linking of proteins through its Ca2+-dependent acyltransferase activity. Moreover, it enhances the interactions between fibronectin and integrins, which in turn mediates the adhesion, migration, and motility of the cells. TGase 2 is also a key player in the pathogenesis of fibrosis. In this study, we investigated whether TGase 2 is present at the biomaterial tissue interface and might serve as an informative biomarker for the visualization of tissue response toward gelatin-based biomaterials. Two differently cross-linked hydrogels were used, which were obtained by the reaction of gelatin with lysine diisocyanate ethyl ester. The overall expression of TGase 2 by endothelial cells, macrophages, and granulocytes was partly influenced by contact to the hydrogels or their degradation products, although no clear correlation was evidenced. In contrast, the secretion of TGase 2 differed remarkably between the different cells, indicating that it might be involved in the cellular reaction toward gelatin-based hydrogels. The hydrogels were implanted subcutaneously in immunocompetent, hairless SKH1-Elite mice. Ex vivo immunohistochemical analysis of tissue sections over 112 days revealed enhanced expression of TGase 2 around the hydrogels, in particular at days 14 and 21 post-implantation. The incorporation of fluorescently labeled cadaverine derivatives for the detection of active TGase 2 was in accordance with the results of the expression analysis. The presence of an irreversible inhibitor of TGase 2 led to attenuated incorporation of the cadaverines, which verified the catalytic action of TGase 2. Our in vitro and ex vivo results verified TGase 2 as a potential biomarker for tissue response toward gelatin-based hydrogels. In vivo, no TGase 2 activity was detectable, which is mainly attributed to the unfavorable physicochemical properties of the cadaverine probe used.},
  language  = {en}
}
@article{ZhangBehlPengetal.2019,
  author    = {Zhang, Pengfei and Behl, Marc and Peng, Xingzhou and Balk, Maria and Lendlein, Andreas},
  title     = {Chemoresponsive Shape-Memory Effect of Rhodium-Phosphine Coordination Polymer Networks},
  series = {Chemistry of materials : a publication of the American Chemical Society},
  volume    = {31},
  journal   = {Chemistry of materials : a publication of the American Chemical Society},
  number    = {15},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {0897-4756},
  doi       = {10.1021/acs.chemmater.9b00363},
  pages     = {5402 -- 5407},
  year      = {2019},
  abstract  = {Chemoresponsive polymers are of technological significance for smart sensors or systems capable of molecular recognition. An important key requirement for these applications is the material's structural integrity after stimulation. We explored whether covalently cross-linked metal ion-phosphine coordination polymers (MPN) can be shaped into any temporary shape and are capable of recovering from this upon chemoresponsive exposure to triphenylphosphine (Ph3P) ligands, whereas the MPN provide structural integrity. Depending on the metal-ion concentration used during synthesis of the MPN, the degree of swelling of the coordination polymer networks could be adjusted. Once the MPN was immersed into Ph3P solution, the reversible ligand-exchange reaction between the metal ions and the free Ph3P in solution causes a decrease of the coordination cross-link density in MPN again. The Ph3P-treated MPN was able to maintain its original shape, indicating a certain stability of shape even after stimulation. In this way, chemoresponsive control of the elastic properties (increase in volume and decrease of mechanical strength) of the MPN was demonstrated. This remarkable behavior motivated us to explore whether the MPN are capable of a chemoresponsive shape-memory effect. In initial experiments, shape fixity of around 60\% and shape recovery of almost 90\% were achieved when the MPN was exposed to Ph3P in case of rhodium. Potential applications for chemoresponsive shape-memory systems could be shapable semiconductors, e.g., for lighting or catalysts, which provide catalytic activity on demand.},
  language  = {en}
}
@article{BhuvaneshMachatschekLysyakovaetal.2019,
  author    = {Bhuvanesh, Thanga and Machatschek, Rainhard Gabriel and Lysyakova, Liudmila and Kratz, Karl and Schulz, Burkhard and Ma, Nan and Lendlein, Andreas},
  title     = {Collagen type-IV Langmuir and Langmuir-Schafer layers as model biointerfaces to direct stem cell adhesion},
  series = {Biomedical materials : materials for tissue engineering and regenerative medicine},
  volume    = {14},
  journal   = {Biomedical materials : materials for tissue engineering and regenerative medicine},
  number    = {2},
  publisher = {Inst. of Physics Publ.},
  address   = {Bristol},
  issn      = {1748-6041},
  doi       = {10.1088/1748-605X/aaf464},
  pages     = {17},
  year      = {2019},
  abstract  = {In biomaterial development, the design of material surfaces that mimic the extra-cellular matrix (ECM) in order to achieve favorable cellular instruction is rather challenging. Collagen-type IV (Col-IV), the major scaffolding component of Basement Membranes (BM), a specialized ECM with multiple biological functions, has the propensity to form networks by self-assembly and supports adhesion of cells such as endothelial cells or stem cells. The preparation of biomimetic Col-IV network-like layers to direct cell responses is difficult. We hypothesize that the morphology of the layer, and especially the density of the available adhesion sites, regulates the cellular adhesion to the layer. The Langmuir monolayer technique allows for preparation of thin layers with precisely controlled packing density at the air-water (A-W) interface. Transferring these layers onto cell culture substrates using the Langmuir-Schafer (LS) technique should therefore provide a pathway for preparation of BM mimicking layers with controlled cell adherence properties. In situ characterization using ellipsometry and polarization modulation-infrared reflection absorption spectroscopy of Col-IV layer during compression at the A-W interface reveal that there is linear increase of surface molecule concentration with negligible orientational changes up to a surface pressure of 25 mN m(-1). Smooth and homogeneous Col-IV network-like layers are successfully transferred by LS method at 15 mN m(-1) onto poly(ethylene terephthalate) (PET), which is a common substrate for cell culture. In contrast, the organization of Col-IV on PET prepared by the traditionally employed solution deposition method results in rather inhomogeneous layers with the appearance of aggregates and multilayers. Progressive increase in the number of early adherent mesenchymal stem cells (MSCs) after 24 h by controlling the areal Col-IV density by LS transfer at 10, 15 and 20 mN m(-1) on PET is shown. The LS method offers the possibility to control protein characteristics on biomaterial surfaces such as molecular density and thereby, modulate cell responses.},
  language  = {en}
}
@article{DengZouWangetal.2019,
  author    = {Deng, Zijun and Zou, Jie and Wang, Weiwei and Nie, Yan and Tung, Wing-Tai and Ma, Nan and Lendlein, Andreas},
  title     = {Dedifferentiation of mature adipocytes with periodic exposure to cold},
  series = {Clinical hemorheology and microcirculation : blood flow and vessels},
  volume    = {71},
  journal   = {Clinical hemorheology and microcirculation : blood flow and vessels},
  number    = {4},
  publisher = {IOS Press},
  address   = {Amsterdam},
  issn      = {1386-0291},
  doi       = {10.3233/CH-199005},
  pages     = {415 -- 424},
  year      = {2019},
  abstract  = {Lipid-containing adipocytes can dedifferentiate into fibroblast-like cells under appropriate culture conditions, which are known as dedifferentiated fat (DFAT) cells. However, the relative low dedifferentiation efficiency with the established protocols limit their widespread applications. In this study, we found that adipocyte dedifferentiation could be promoted via periodic exposure to cold (10 degrees C) in vitro. The lipid droplets in mature adipocytes were reduced by culturing the cells in periodic cooling/heating cycles (10-37 degrees C) for one week. The periodic temperature change led to the down-regulation of the adipogenic genes (FABP4, Leptin) and up-regulation of the mitochondrial uncoupling related genes (UCP1, PGC-1 alpha, and PRDM16). In addition, the enhanced expression of the cell proliferation marker Ki67 was observed in the dedifferentiated fibroblast-like cells after periodic exposure to cold, as compared to the cells cultured in 37 degrees C. Our in vitro model provides a simple and effective approach to promote lipolysis and can be used to improve the dedifferentiation efficiency of adipocytes towards multipotent DFAT cells.},
  language  = {en}
}
@article{NieWangXuetal.2019,
  author    = {Nie, Yan and Wang, Weiwei and Xu, Xun and Zou, Jie and Bhuvanesh, Thanga and Schulz, Burkhard and Ma, Nan and Lendlein, Andreas},
  title     = {Enhancement of human induced pluripotent stem cells adhesion through multilayer laminin coating},
  series = {Clinical hemorheology and microcirculation : blood flow and vessels},
  volume    = {70},
  journal   = {Clinical hemorheology and microcirculation : blood flow and vessels},
  number    = {4},
  publisher = {IOS Press},
  address   = {Amsterdam},
  issn      = {1386-0291},
  doi       = {10.3233/CH-189318},
  pages     = {531 -- 542},
  year      = {2019},
  abstract  = {Bioengineered cell substrates are a highly promising tool to govern the differentiation of stem cells in vitro and to modulate the cellular behavior in vivo. While this technology works fine for adult stem cells, the cultivation of human induced pluripotent stem cells (hiPSCs) is challenging as these cells typically show poor attachment on the bioengineered substrates, which among other effects causes substantial cell death. Thus, very limited types of surfaces have been demonstrated suitable for hiPSC cultures. The multilayer coating approach that renders the surface with diverse chemical compositions, architectures, and functions can be used to improve the adhesion of hiPSCs on the bioengineered substrates. We hypothesized that a multilayer formation based on the attraction of molecules with opposite charges could functionalize the polystyrene (PS) substrates to improve the adhesion of hiPSCs. Polymeric substrates were stepwise coated, first with dopamine to form a polydopamine (PDA) layer, second with polylysine and last with Laminin-521. The multilayer formation resulted in the variation of hydrophilicity and chemical functionality of the surfaces. Hydrophilicity was detected using captive bubble method and the amount of primary and secondary amines on the surface was quantified by fluorescent staining. The PDA layer effectively immobilized the upper layers and thereby improved the attachment of hiPSCs. Cell adhesion was enhanced on the surfaces coated with multilayers, as compared to those without PDA and/or polylysine. Moreover, hiPSCs spread well over this multilayer laminin substrate. These cells maintained their proliferation capacity and differentiation potential. The multilayer coating strategy is a promising attempt for engineering polymer-based substrates for the cultivation of hiPSCs and of interest for expanding the application scope of hiPSCs.},
  language  = {en}
}
@article{MachatschekLendlein2019,
  author    = {Machatschek, Rainhard Gabriel and Lendlein, Andreas},
  title     = {Fundamental insights in PLGA degradation from thin film studies},
  series = {Journal of controlled release : official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems},
  volume    = {319},
  journal   = {Journal of controlled release : official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems},
  publisher = {Elsevier},
  address   = {New York},
  issn      = {0168-3659},
  doi       = {10.1016/j.jconrel.2019.12.044},
  pages     = {276 -- 284},
  year      = {2019},
  abstract  = {Poly(lactide-co-glycolide)s are commercially available degradable implant materials, which are typically selected based on specifications given by the manufacturer, one of which is their molecular weight. Here, we address the question whether variations in the chain length and their distribution affect the degradation behavior of Poly[(rac-lactide)-co-glycolide]s (PDLLGA). The hydrolysis was studied in ultrathin films at the air-water interface in order to rule out any morphological effects. We found that both for purely hydrolytic degradation as well as under enzymatic catalysis, the molecular weight has very little effect on the overall degradation kinetics of PDLLGAs. The quantitative analysis suggested a random scission mechanism. The monolayer experiments showed that an acidic micro-pH does not accelerate the degradation of PDLLGAs, in contrast to alkaline conditions. The degradation experiments were combined with interfacial rheology measurements, which showed a drastic decrease of the viscosity at little mass loss. The extrapolated molecular weight behaved similar to the viscosity, dropping to a value near to the solubility limit of PDLLGA oligomers before mass loss set in. This observation suggests a solubility controlled degradation of PDLLGA. Conclusively, the molecular weight affects the degradation of PDLLGA devices mostly in indirect ways, e.g. by determining their morphology and porosity during fabrication. Our study demonstrates the relevance of the presented Langmuir degradation method for the design of controlled release systems.},
  language  = {en}
}
@article{BalkBehlLendlein2019,
  author    = {Balk, Maria and Behl, Marc and Lendlein, Andreas},
  title     = {Hydrolytic Degradation of Actuators Based on Copolymer Networks From Oligo(epsilon-caprolactone) Dimethacrylate and n-Butyl Acrylate},
  series = {MRS advances},
  volume    = {4},
  journal   = {MRS advances},
  number    = {21},
  publisher = {Cambridge Univ. Press},
  address   = {New York},
  issn      = {2059-8521},
  doi       = {10.1557/adv.2019.202},
  pages     = {1193 -- 1205},
  year      = {2019},
  abstract  = {Shape-memory polymer actuators often contain crystallizable polyester segments. Here, the influence of accelerated hydrolytic degradation on the actuation performance in copolymer networks based on oligo(epsilon-caprolactone) dimethacrylate (OCL) and n-butyl acrylate is studied The semi-crystalline OCL was utilized as crosslinker with molecular weights of 2.3 and 15.2 kg.mol(-1) (ratio: 1:1 wt\%) and n-butyl acrylate (25 wt\% relative to OCL content) acted as softening agent creating the polymer main chain segments within the network architecture. The copolymer networks were programmed by 50\% elongation and were degraded by means of alkaline hydrolysis utilizing sodium hydroxide solution (pH = 13). Experiments were performed in the range of the broad melting range of the actuators at 40 degrees C. The degradation of test specimen was monitored by the sample mass, which was reduced by 25 wt\% within 105 d .45 degradation products, fragments of OCL with molecular masses ranging from 400 to 50.000 g.mol(-1) could be detected by NMR spectroscopy and GPC measurements. The cleavage of ester groups included in OCL segments resulted in a decrease of the melting temperature (T-m) related to the actuator domains (amorphous at the temperature of degradation) and simultaneously, the T-m associated to the skeleton domain was increased (semi-crystalline at the temperature of degradation). The alkaline hydrolysis decreased the polymer chain orientation of OCL domains until a random alignment of crystalline domains was obtained. This result was confirmed by cyclic thermomechanical actuation tests. The performance of directed movements decreased almost linearly as function of degradation time resulting in the loss of functionality when the orientation of polymer chains disappeared. Here, actuators were able to provide reversible movements until 91 d when the accelerated bulk degradation procedure using alkaline hydrolysis (pH = 13) was applied. Accordingly, a lifetime of more than one year can be guaranteed under physiological conditions (pH = 7.4) when, e.g., artificial muscles for biomimetic robots as potential application for these kind of shape-memory polymer actuators will be addressed.},
  language  = {en}
}
@article{MazurekBudzyńskaBehlRazzaqetal.2019,
  author    = {Mazurek-Budzyńska, Magdalena and Behl, Marc and Razzaq, Muhammad Yasar and N{\"o}chel, Ulrich and Rokicki, Gabriel and Lendlein, Andreas},
  title     = {Hydrolytic stability of aliphatic poly(carbonate-urea-urethane)s: Influence of hydrocarbon chain length in soft segment},
  series = {Polymer Degradation and Stability},
  volume    = {161},
  journal   = {Polymer Degradation and Stability},
  publisher = {Elsevier},
  address   = {Oxford},
  issn      = {0141-3910},
  pages     = {283 -- 297},
  year      = {2019},
  abstract  = {Poly(carbonate-urethane)s (PCUs) exhibit improved resistance to hydrolytic degradation and in vivo stress cracking compared to poly(ester-urethane)s and their degradation leads to lower inflammation of the surrounding tissues. Therefore, PCUs are promising implant materials and are considered for devices such as artificial heart or spine implants. In this work, the hydrolytic stability of different poly(carbonate-urethane-urea)s (PCUUs) was studied under variation of the length of hydrocarbon chain (6, 9, 10, and 12 methylene units) between the carbonate linkages in the precursors. PCUUs were synthesized from isophorone diisocyanate and oligo(alkylene carbonate) diols using the moisture-cure method. The changes of sample weight, thermal and mechanical properties, morphology, as well as the degradation products after immersion in a buffer solution (PBS, pH = 7.4) for up to 10 weeks at 37 degrees C were monitored and analyzed. In addition, mechanical properties after 20 weeks (in PBS, 37 degrees C) were investigated. The gel content was determined based on swelling experiments in chloroform. Based on the DSC analysis, slight increases of melting transitions of PCUUs were observed, which were attributed to structure reorganization related to annealing at 37 degrees C rather than to the degradation of the PCUU. Tensile strength after 20 weeks of all investigated samples remained in the range of 29-39 MPa, whereas the elongation at break e(m) decreased only slightly and remained in the range between 670 and 800\%. Based on the characterization of degradation products after up to 10 weeks of immersion it was assessed that oligomers are mainly consisting of hard segments containing urea linkages, which could be assigned to hindered-urea dissociation mechanism. The investigations confirmed good resistance of PCUUs to hydrolysis. Only minor changes in the crystallinity, as well as thermal and mechanical properties were observed and depended on hydrocarbon chain length in soft segment of PCUUs. (C) 2019 Published by Elsevier Ltd.},
  language  = {en}
}