@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{DalBiancoWischkeZhouetal.2017, author = {Dal Bianco, Andrea and Wischke, Christian and Zhou, Shuo and Lendlein, Andreas}, title = {Controlling surface properties and permeability of polyglycerol network films}, series = {Polymers for advanced technologies}, volume = {28}, journal = {Polymers for advanced technologies}, publisher = {Wiley}, address = {Hoboken}, issn = {1042-7147}, doi = {10.1002/pat.3917}, pages = {1263 -- 1268}, year = {2017}, abstract = {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.}, language = {en} } @misc{BalkGrijpmaLendlein2017, author = {Balk, Maria and Grijpma, Dirk W. and Lendlein, Andreas}, title = {Design and processing of advanced functional polymers for medicine}, series = {Polymers for advanced technologies}, volume = {28}, journal = {Polymers for advanced technologies}, publisher = {Wiley}, address = {Hoboken}, issn = {1042-7147}, doi = {10.1002/pat.3980}, pages = {1203 -- 1205}, year = {2017}, language = {en} } @article{PilusoLendleinNeffe2017, author = {Piluso, Susanna and Lendlein, Andreas and Neffe, Axel T.}, title = {Enzymatic action as switch of bulk to surface degradation of clicked gelatin-based networks}, series = {Polymers for advanced technologies}, volume = {28}, journal = {Polymers for advanced technologies}, publisher = {Wiley}, address = {Hoboken}, issn = {1042-7147}, doi = {10.1002/pat.3962}, pages = {1318 -- 1324}, year = {2017}, abstract = {Polymer degradation occurs under physiological conditions in vitro and in vivo, especially when bonds susceptible to hydrolysis are present in the polymer. Understanding of the degradation mechanism, changes of material properties over time, and overall rate of degradation is a necessary prerequisite for the knowledge-based design of polymers with applications in biomedicine. Here, hydrolytic degradation studies of gelatin-based networks synthesized by copper-catalyzed azide-alkyne cycloaddition reaction are reported, which were performed with or without addition of an enzyme. In all cases, networks with a stilbene as crosslinker proofed to be more resistant to degradation than when an octyl diazide was used. Without addition of an enzyme, the rate of degradation was ruled by the crosslinking density of the network and proceeded via a bulk degradation mechanism. Addition of Clostridium histolyticum collagenase resulted in a much enhanced rate of degradation, which furthermore occurred via surface erosion. The mesh size of the hydrogels (>7nm) was in all cases larger than the hydrodynamic radius of the enzyme (4.5nm) so that even in very hydrophilic networks with large mesh size enzymes may be used to induce a fast surface degradation mechanism. This observation is of general interest when designing hydrogels to be applied in the presence of enzymes, as the degradation mechanism and material performance are closely interlinked. Copyright (c) 2016 John Wiley \& Sons, Ltd.}, 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} } @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{BrunacciWischkeNaolouetal.2017, author = {Brunacci, Nadia and Wischke, Christian and Naolou, Toufik and Neffe, Axel T. and Lendlein, Andreas}, title = {Influence of surfactants on depsipeptide submicron particle formation}, series = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {116}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0939-6411}, doi = {10.1016/j.ejpb.2016.11.011}, pages = {61 -- 65}, year = {2017}, abstract = {Surfactants are required for the formation and stabilization of hydrophobic polymeric particles in aqueous environment. In order to form submicron particles of varying sizes from oligo[3-(S)-sec-butylmorpholine-2,5-dione]diols ((OBMD)-diol), different surfactants were investigated. As new surfactants, four-armed star-shaped oligo(ethylene glycol)s of molecular weights of 5-20 kDa functionalized with desamino-tyrosine (sOEG-DAT) resulted in smaller particles with lower PDI than with desaminotyrosyl tyrosine (sOEG-DATT) in an emulsion/solvent evaporation method. In a second set of experiments, sOEG-DAT of M-n= 10 kDa was compared with the commonly employed emulsifiers polyvinylalcohol (PVA), polyoxyethylene (20) sorbitan monolaurate (Tween 20), and D-alpha-tocopherol polyethylene glycol succinate (VIT E-TPGS) for OBMD particle preparation. sOEG-DAT allowed to systematically change sizes in a range of 300 up to 900 nm with narrow polydispersity, while in the other cases, a lower size range (250-400 nm, PVA; 300 nm, Tween 20) or no effective particle formation was observed. The ability of tailoring particle size in a broad range makes sOEG-DAT of particular interest for the formation of oligodepsipeptide particles, which can further be investigated as drug carriers for controlled delivery. (C) 2016 Elsevier B.V. All rights reserved.}, language = {en} } @article{BhuvaneshSaretiaRochetal.2017, author = {Bhuvanesh, Thanga and Saretia, Shivam and Roch, Toralf and Sch{\"o}ne, Anne-Christin and Rottke, Falko O. and Kratz, Karl and Wang, Weiwei and Ma, Nan and Schulz, Burkhard and Lendlein, Andreas}, title = {Langmuir-Schaefer films of fibronectin as designed biointerfaces for culturing stem cells}, series = {Polymers for advanced technologies}, volume = {28}, journal = {Polymers for advanced technologies}, publisher = {Wiley}, address = {Hoboken}, issn = {1042-7147}, doi = {10.1002/pat.3910}, pages = {1305 -- 1311}, year = {2017}, abstract = {Glycoproteins adsorbing on an implant upon contact with body fluids can affect the biological response in vitro and in vivo, depending on the type and conformation of the adsorbed biomacromolecules. However, this process is poorly characterized and so far not controllable. Here, protein monolayers of high molecular cohesion with defined density are transferred onto polymeric substrates by the Langmuir-Schaefer (LS) technique and were compared with solution deposition (SO) method. It is hypothesized that on polydimethylsiloxane (PDMS), a substrate with poor cell adhesion capacity, the fibronectin (FN) layers generated by the LS and SO methods will differ in their organization, subsequently facilitating differential stem cell adhesion behavior. Indeed, atomic force microscopy visualization and immunofluorescence images indicated that organization of the FN layer immobilized on PDMS was uniform and homogeneous. In contrast, FN deposited by SO method was rather heterogeneous with appearance of structures resembling protein aggregates. Human mesenchymal stem cells showed reduced absolute numbers of adherent cells, and the vinculin expression seemed to be higher and more homogenously distributed after seeding on PDMS equipped with FN by LS in comparison with PDMS equipped with FN by SO. These divergent responses could be attributed to differences in the availability of adhesion molecule ligands such as the Arg-Gly-Asp (RGD) peptide sequence presented at the interface. The LS method allows to control the protein layer characteristics, including the thickness and the protein orientation or conformation, which can be harnessed to direct stem cell responses to defined outcomes, including migration and differentiation. Copyright (c) 2016 John Wiley \& Sons, Ltd.}, language = {en} } @article{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{HeuchelGerberKratzetal.2017, author = {Heuchel, Matthias and Gerber, David and Kratz, Karl and Lendlein, Andreas}, title = {Morphological analysis of differently sized highly porous poly(ether imide) microparticles by mercury porosimetry}, series = {Polymers for advanced technologies}, volume = {28}, journal = {Polymers for advanced technologies}, publisher = {Wiley}, address = {Hoboken}, issn = {1042-7147}, doi = {10.1002/pat.3973}, pages = {1269 -- 1277}, year = {2017}, abstract = {Highly porous poly(ether imide) (PEI) microparticles prepared by a spraying/coagulation process are discussed as candidate adsorber materials for apheresis applications, i.e. removal of uremic toxins from the blood of renal failure patients. PEI particles obtained by the aforementioned procedure can have a broad size distribution with particle diameters ranging from 20 to 800 mu m. In order to further estimate the adsorption behavior of PEI microparticles packed in application relevant apheresis modules, a quantitative information about the relation between particle size and pore morphology is required. In this study, we explored whether the intraparticle porosity of PEI microparticles varies with altering the diameter of the particulate adsorbers. By an analytical wet sieving procedure, the obtained PEI microparticles were separated into five size fractions, which were analyzed by mercury intrusion porosimetry, nitrogen adsorption, and scanning electron microscopy. Mercury intrusion porosimetry revealed for all size fractions high porosity values in the range from 78\% to 84\% with pore diameters in the range from 10 to 1000nm. A bimodal pore size distribution was found having a first peak at around 100nm, while a second pronounced peak maximum was found at higher pore sizes that increased with raising particle diameter from 300nm for the smallest particle size fraction (50-100 mu m) to 700nm for particles with a diameter of 200 to 250 mu m. Based on these findings, it can be assumed that the main PEI particle size fraction (200-250 mu m) should exhibit the highest adsorption capacity in an apheresis module. Copyright (c) 2016 John Wiley \& Sons, Ltd.}, language = {en} }