@article{ZouWangNeffeetal.2017, author = {Zou, Jie and Wang, Weiwei and Neffe, Axel T. and Xu, Xun and Li, Zhengdong and Deng, Zijun and Sun, Xianlei and Ma, Nan and Lendlein, Andreas}, title = {Adipogenic differentiation of human adipose derived mesenchymal stem cells in 3D architectured gelatin based hydrogels (ArcGel)}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {67}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, number = {3-4}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-179210}, pages = {297 -- 307}, year = {2017}, abstract = {Polymeric matrices mimicking multiple functions of the ECM are expected to enable a material induced regeneration of tissues. Here, we investigated the adipogenic differentiation of human adipose derived mesenchymal stem cells (hADSCs) in a 3D architectured gelatin based hydrogel (ArcGel) prepared from gelatin and L-lysine diisocyanate ethyl ester (LDI) in an one-step process, in which the formation of an open porous morphology and the chemical network formation were integrated. The ArcGel was designed to support adipose tissue regeneration with its 3D porous structure, high cell biocompatibility, and mechanical properties compatible with human subcutaneous adipose tissue. The ArcGel could support initial cell adhesion and survival of hADSCs. Under static culture condition, the cells could migrate into the inner part of the scaffold with a depth of 840 +/- 120 mu m after 4 days, and distributed in the whole scaffold (2mm in thickness) within 14 days. The cells proliferated in the scaffold and the fold increase of cell number after 7 days of culture was 2.55 +/- 0.08. The apoptotic rate of hADSCs in the scaffold was similar to that of cells maintained on tissue culture plates. When cultured in adipogenic induction medium, the hADSCs in the scaffold differentiated into adipocytes with a high efficiency (93 +/- 1\%). Conclusively, this gelatin based 3D scaffold presented high cell compatibility for hADSC cultivation and differentiation, which could serve as a potential implant material in clinical applications for adipose tissue reparation and regeneration.}, language = {en} } @article{LiXuWangetal.2017, author = {Li, Zhengdong and Xu, Xun and Wang, Weiwei and Kratz, Karl and Sun, Xianlei and Zou, Jie and Deng, Zijun and Jung, Friedrich Wilhelm and Gossen, Manfred and Ma, Nan and Lendlein, Andreas}, title = {Modulation of the mesenchymal stem cell migration capacity via preconditioning with topographic microstructure}, series = {Clinical hemorheology and microcirculation : blood flow and vessels}, volume = {67}, journal = {Clinical hemorheology and microcirculation : blood flow and vessels}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1386-0291}, doi = {10.3233/CH-179208}, pages = {267 -- 278}, year = {2017}, abstract = {Controlling mesenchymal stem cells (MSCs) behavior is necessary to fully exploit their therapeutic potential. Various approaches are employed to effectively influence the migration capacity of MSCs. Here, topographic microstructures with different microscale roughness were created on polystyrene (PS) culture vessel surfaces as a feasible physical preconditioning strategy to modulate MSC migration. By analyzing trajectories of cells migrating after reseeding, we demonstrated that the mobilization velocity of human adipose derived mesenchymal stem cells (hADSCs) could be promoted by and persisted after brief preconditioning with the appropriate microtopography. Moreover, the elevated activation levels of focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) in hADSCs were also observed during and after the preconditioning process. These findings underline the potential enhancement of in vivo therapeutic efficacy in regenerative medicine via transplantation of topographic microstructure preconditioned stem cells.}, language = {en} } @article{YouBehlLoewenbergetal.2017, author = {You, Zewang and Behl, Marc and L{\"o}wenberg, Candy and Lendlein, Andreas}, title = {pH-sensitivity and conformation change of the n-terminal methacrylated peptide VK20}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {2}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, publisher = {Cambridge University Press}, address = {Cambridge}, issn = {2059-8521}, doi = {10.1557/adv.2017.491}, pages = {2571 -- 2579}, year = {2017}, abstract = {N-terminal methacrylation of peptide MAXI, which is capable of conformational changes variation of the pH, results in a peptide, named VK20. Increasing the reactivity of this terminal group enables further coupling reactions or chemical modifications of the peptidc. However, this end group functionalization may influence the ability of confonnational changes of VK20; as well as its properties. In this paper; the influence of pH on the transition between random coil and beta-sheet conformation of VK20; including the transition kinetics, were investigated. At pH values of 9 and higher, the kinetics beta-sheet formation increased tor VK(2 0, compared to MAXI. The self-assembly into beta-sheets recognized by the formation of a physically crosslinked gel was furthermore indicated by a significant increase of G. An increase in pH (from 9 to 9.5) led to a faster gelation of the peptide VK20. Simultaneously, G was increased from 460 +/- 70 Pa (at pH 9) to 1520 +/- 180 Pa (at pH 9.5). At the nanoscale, the gel showed a highly interconnected fibrillar/network structure with uniform fibril widths of approximately 3.4 +/- 0.5 nm (N=30). The recovery of the peptide conformation back to random coil resulted in the dissolution of the gel; whereby the kinetics of the recovery depended on the pH. Conclusively, the ability of MAXI to undergo confommtional changes was not affected by N-terminal methacrylation whereas the kinetics of pH-sensitive beta-sheet formations has been increased.}, language = {en} } @article{PengBehlZhangetal.2017, author = {Peng, Xingzhou and Behl, Marc and Zhang, Pengfei and Mazurek-Budzyńska, Magdalena and Feng, Yakai and Lendlein, Andreas}, title = {Synthesis and characterization of multiblock poly(ester-amide-urethane)s}, series = {MRS advances : a journal of the Materials Research Society (MRS)}, volume = {2}, journal = {MRS advances : a journal of the Materials Research Society (MRS)}, publisher = {Cambridge University Press}, address = {Cambridge}, issn = {2059-8521}, doi = {10.1557/adv.2017.486}, pages = {2551 -- 2559}, year = {2017}, abstract = {In this study, a multiblock copolymer containing oligo(3-methyl-morpholine-2, 5-dione) (oMMD) and oligo(3-sec-butyl-morpholine-2, 5-dione) (oBMD) building blocks obtained by ring-opening polymerization (ROP) of the corresponding monomers, was synthesized in a polyaddition reaction using an aliphatic diisocyanate. The multiblock copolymer (pBMD-MMD) provided a molecular weight of 40, 000 g·mol-1, determined by gel permeation chromatography (GPC). Incorporation of both oligodepsipeptide segments in multiblock copolymers was confirmed by 1H NMR and Matrix Assisted Laser Desorption/Ionization Time Of Flight Mass Spectroscopy (MALDI-TOF MS) analysis. pBMD-MMD showed two separated glass transition temperatures (61 °C and 74 °C) indicating a microphase separation. Furthermore, a broad glass transition was observed by DMTA, which can be attributed to strong physical interaction i.e. by H-bonds formed between amide, ester, and urethane groups of the investigated copolymers. The obtained multiblock copolymer is supposed to own the capability to exhibit strong physical interactions.}, language = {en} } @article{LiuRazzaqRudolphetal.2017, author = {Liu, Yue and Razzaq, Muhammad Yasar and Rudolph, Tobias and Fang, Liang and Kratz, Karl and Lendlein, Andreas}, title = {Two-Level Shape Changes of Polymeric Microcuboids Prepared from Crystallizable Copolymer Networks}, series = {Macromolecules : a publication of the American Chemical Society}, volume = {50}, journal = {Macromolecules : a publication of the American Chemical Society}, publisher = {American Chemical Society}, address = {Washington}, issn = {0024-9297}, doi = {10.1021/acs.macromol.6b02237}, pages = {2518 -- 2527}, year = {2017}, abstract = {Polymeric microdevices bearing features like nonspherical shapes or spatially segregated surface properties are of increasing importance in biological and medical analysis, drug delivery, and bioimaging or microfluidic systems as well as in micromechanics, sensors, information storage, or data carrier devices. Here, a method to fabricate programmable microcuboids with shape-memory capability and the quantification of their recovery at different levels is reported. The method uses the soft lithographic technique to create microcuboids with well-defined sizes and surface properties. Microcuboids having an edge length of 25 mu m and a height of 10 mu m were prepared from cross-linked poly[ethylene-co-(vinyl acetate)] (cPEVA) with different vinyl acetate contents and were programmed by compression with various deformation degrees at elevated temperatures. The microlevel shape-recovery of the cuboidal geometry during heating was monitored by optical microscopy (OM) and atomic force microscopy (AFM) studying the related changes in the projected area (PA) or height, while the nanolevel changes of the nanosurface roughness were investigated by in situ AFM. The shape-memory effect at the microlevel was quantified by the recovery ratio of cuboids (R-r,R-micro), while at the. nanolevel, the recovery ratio of the nanoroughness (R-r,R-nano) was measured. The values of R-r,R-micro,,micro could be tailored in a range from 42 +/- 1\% to 102 +/- 1\% and Rr,nano from 89 +/- 6\% to 136 +/- 21\% depending on the applied compression ratio and the amount of vinyl acetate content in the cPEVA microcuboids.}, language = {en} } @article{HaaseKrostSauteretal.2017, author = {Haase, Tobias and Krost, Annalena and Sauter, Tilman and Kratz, Karl and Peter, Jan and Kamann, Stefanie and Jung, Friedrich and Lendlein, Andreas and Zohlnh{\"o}fer, Dietlind and R{\"u}der, Constantin}, title = {In vivo biocompatibility assessment of poly (ether imide) electrospun scaffolds}, series = {Journal of Tissue Engineering and Regenerative Medicine}, volume = {11}, journal = {Journal of Tissue Engineering and Regenerative Medicine}, number = {4}, publisher = {Wiley}, address = {Hoboken}, issn = {1932-6254}, doi = {10.1002/term.2002}, pages = {1034 -- 1044}, year = {2017}, abstract = {Poly(ether imide) (PEI), which can be chemically functionalized with biologically active ligands, has emerged as a potential biomaterial for medical implants. Electrospun PEI scaffolds have shown advantageous properties, such as enhanced endothelial cell adherence, proliferation and low platelet adhesion in in vitro experiments. In this study, the in vivo behaviour of electrospun PEI scaffolds and PEI films was examined in a murine subcutaneous implantation model. Electrospun PEI scaffolds and films were surgically implanted subcutaneously in the dorsae of mice. The surrounding subcutaneous tissue response was examined via histopathological examination at 7 and 28days after implantation. No serious adverse events were observed for both types of PEI implants. The presence of macrophages or foreign body giant cells in the vicinity of the implants and the formation of a fibrous capsule indicated a normal foreign body reaction towards PEI films and scaffolds. Capsule thickness and inflammatory infiltration cells significantly decreased for PEI scaffolds during days 7-28 while remaining unchanged for PEI films. The infiltration of cells into the implant was observed for PEI scaffolds 7days after implantation and remained stable until 28days of implantation. Additionally some, but not all, PEI scaffold implants induced the formation of functional blood vessels in the vicinity of the implants. Conclusively, this study demonstrates the in vivo biocompatibility of PEI implants, with favourable properties of electrospun PEI scaffolds regarding tissue integration and wound healing.}, language = {en} } @article{ZhangSaidWischkeetal.2017, author = {Zhang, Nan and Said, Andre and Wischke, Christian and Kral, Vivian and Brodwolf, Robert and Volz, Pierre and Boreham, Alexander and Gerecke, Christian and Li, Wenzhong and Neffe, Axel T. and Kleuser, Burkhard and Alexiev, Ulrike and Lendlein, Andreas and Sch{\"a}fer-Korting, Monika}, title = {Poly[acrylonitrile-co-(N-vinyl pyrrolidone)] nanoparticles - Composition-dependent skin penetration enhancement of a dye probe and biocompatibility}, series = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {116}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2016.10.019}, pages = {66 -- 75}, year = {2017}, abstract = {Nanoparticles can improve topical drug delivery: size, surface properties and flexibility of polymer nanoparticles are defining its interaction with the skin. Only few studies have explored skin penetration for one series of structurally related polymer particles with systematic alteration of material composition. Here, a series of rigid poly[acrylonitrile-co-(N-vinyl pyrrolidone)] model nanoparticles stably loaded with Nile Red or Rhodamin B, respectively, was comprehensively studied for biocompatibility and functionality. Surface properties were altered by varying the molar content of hydrophilic NVP from 0 to 24.1\% and particle size ranged from 35 to 244 nm. Whereas irritancy and genotoxicity were not revealed, lipophilic and hydrophilic nanoparticles taken up by keratinocytes affected cell viability. Skin absorption of the particles into viable skin ex vivo was studied using Nile Red as fluorescent probe. Whilst an intact stratum corneum efficiently prevented penetration, almost complete removal of the horny layer allowed nanoparticles of smaller size and hydrophilic particles to penetrate into viable epidermis and dermis. Hence, systematic variations of nanoparticle properties allows gaining insights into critical criteria for biocompatibility and functionality of novel nanocarriers for topical drug delivery and risks associated with environmental exposure.}, language = {en} } @article{BrunacciWischkeNaolouetal.2017, author = {Brunacci, Nadia and Wischke, Christian and Naolou, Toufik and Neffe, Axel T. and Lendlein, Andreas}, title = {Influence of surfactants on depsipeptide submicron particle formation}, series = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {116}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2016.11.011}, pages = {61 -- 65}, year = {2017}, abstract = {Surfactants are required for the formation and stabilization of hydrophobic polymeric particles in aqueous environment. In order to form submicron particles of varying sizes from oligo[3-(S)-sec-butylmorpholine-2,5-dione]diols ((OBMD)-diol), different surfactants were investigated. As new surfactants, four-armed star-shaped oligo(ethylene glycol)s of molecular weights of 5-20 kDa functionalized with desamino-tyrosine (sOEG-DAT) resulted in smaller particles with lower PDI than with desaminotyrosyl tyrosine (sOEG-DATT) in an emulsion/solvent evaporation method. In a second set of experiments, sOEG-DAT of M-n= 10 kDa was compared with the commonly employed emulsifiers polyvinylalcohol (PVA), polyoxyethylene (20) sorbitan monolaurate (Tween 20), and D-alpha-tocopherol polyethylene glycol succinate (VIT E-TPGS) for OBMD particle preparation. sOEG-DAT allowed to systematically change sizes in a range of 300 up to 900 nm with narrow polydispersity, while in the other cases, a lower size range (250-400 nm, PVA; 300 nm, Tween 20) or no effective particle formation was observed. The ability of tailoring particle size in a broad range makes sOEG-DAT of particular interest for the formation of oligodepsipeptide particles, which can further be investigated as drug carriers for controlled delivery. (C) 2016 Elsevier B.V. All rights reserved.}, language = {en} } @misc{NaolouRuehlLendlein2017, author = {Naolou, Toufik and R{\"u}hl, Eckart and Lendlein, Andreas}, title = {Nanocarriers}, series = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {116}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2017.03.004}, pages = {1 -- 3}, year = {2017}, language = {en} } @misc{SchoeneRochSchulzetal.2017, author = {Sch{\"o}ne, Anne-Christin and Roch, Toralf and Schulz, Burkhard and Lendlein, Andreas}, title = {Evaluating polymeric biomaterial-environment interfaces by Langmuir monolayer techniques}, series = {Interface : journal of the Royal Society}, volume = {14}, journal = {Interface : journal of the Royal Society}, publisher = {Royal Society}, address = {London}, issn = {1742-5689}, doi = {10.1098/rsif.2016.1028}, pages = {18}, year = {2017}, abstract = {Polymeric biomaterials are of specific relevance in medical and pharmaceutical applications due to their wide range of tailorable properties and functionalities. The knowledge about interactions of biomaterials with their biological environment is of crucial importance for developing highly sophisticated medical devices. To achieve optimal in vivo performance, a description at the molecular level is required to gain better understanding about the surface of synthetic materials for tailoring their properties. This is still challenging and requires the comprehensive characterization of morphological structures, polymer chain arrangements and degradation behaviour. The review discusses selected aspects for evaluating polymeric biomaterial-environment interfaces by Langmuir monolayer methods as powerful techniques for studying interfacial properties, such as morphological and degradation processes. The combination of spectroscopic, microscopic and scattering methods with the Langmuir techniques adapted to polymers can substantially improve the understanding of their in vivo behaviour.}, language = {en} }