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- ItemRecent Progress and Perspectives in the Electrokinetic Characterization of Polyelectrolyte Films(Basel : MDPI, 2015) Zimmermann, Ralf; Werner, Carsten; Duval, Jérôme F LThe analysis of the charge, structure and molecular interactions of/within polymeric substrates defines an important analytical challenge in materials science. Accordingly, advanced electrokinetic methods and theories have been developed to investigate the charging mechanisms and structure of soft material coatings. In particular, there has been significant progress in the quantitative interpretation of streaming current and surface conductivity data of polymeric films from the application of recent theories developed for the electrohydrodynamics of diffuse soft planar interfaces. Here, we review the theory and experimental strategies to analyze the interrelations of the charge and structure of polyelectrolyte layers supported by planar carriers under electrokinetic conditions. To illustrate the options arising from these developments, we discuss experimental and simulation data for plasma-immobilized poly(acrylic acid) films and for a polyelectrolyte bilayer consisting of poly(ethylene imine) and poly(acrylic acid). Finally, we briefly outline potential future developments in the field of the electrokinetics of polyelectrolyte layers.
- ItemAmphiphilic Copolymers for Versatile, Facile, and In Situ Tunable Surface Biofunctionalization(Weinheim : Wiley-VCH, 2021) Ruland, André; Schenker, Saskia; Schirmer, Lucas; Friedrichs, Jens; Meinhardt, Andrea; Schwartz, Véronique B.; Kaiser, Nadine; Konradi, Rupert; MacDonald, William; Helmecke, Tina; Sikosana, Melissa K.L.N.; Valtin, Juliane; Hahn, Dominik; Renner, Lars D.; Werner, Carsten; Freudenberg, UwePrecision surface engineering is key to advanced biomaterials. A new platform of PEGylated styrene-maleic acid copolymers for adsorptive surface biofunctionalization is reported. Balanced amphiphilicity renders the copolymers water-soluble but strongly affine for surfaces. Fine-tuning of their molecular architecture provides control over adsorptive anchorage onto specific materials-which is why they are referred to as "anchor polymers" (APs)-and over structural characteristics of the adsorbed layers. Conjugatable with an array of bioactives-including cytokine-complexing glycosaminoglycans, cell-adhesion-mediating peptides and antimicrobials-APs can be applied to customize materials for demanding biotechnologies in uniquely versatile, simple, and robust ways. Moreover, homo- and heterodisplacement of adsorbed APs provide unprecedented means of in situ alteration and renewal of the functionalized surfaces. The related options are exemplified with proof-of-concept experiments of controlled bacterial adhesion, human umbilical vein endothelial cell, and induced pluripotent cell growth on AP-functionalized surfaces.
- ItemNon-leaching, Highly Biocompatible Nanocellulose Surfaces That Efficiently Resist Fouling by Bacteria in an Artificial Dermis Model(Washington, DC : ACS Publications, 2020) Hassan, Ghada; Forsman, Nina; Wan, Xing; Keurulainen, Leena; Bimbo, Luis M.; Stehl, Susanne; van Charante, Frits; Chrubasik, Michael; Prakash, Aruna S.; Johansson, Leena-Sisko; Mullen, Declan C.; Johnston, Blair F.; Zimmermann, Ralf; Werner, Carsten; Yli-Kauhaluoma, Jari; Coenye, Tom; Saris, Per E.J.; Österberg, Monika; Moreira, Vânia M.Bacterial biofilm infections incur massive costs on healthcare systems worldwide. Particularly worrisome are the infections associated with pressure ulcers and prosthetic, plastic, and reconstructive surgeries, where staphylococci are the major biofilm-forming pathogens. Non-leaching antimicrobial surfaces offer great promise for the design of bioactive coatings to be used in medical devices. However, the vast majority are cationic, which brings about undesirable toxicity. To circumvent this issue, we have developed antimicrobial nanocellulose films by direct functionalization of the surface with dehydroabietic acid derivatives. Our conceptually unique design generates non-leaching anionic surfaces that reduce the number of viable staphylococci in suspension, including drug-resistant Staphylococcus aureus, by an impressive 4-5 log units, upon contact. Moreover, the films clearly prevent bacterial colonization of the surface in a model mimicking the physiological environment in chronic wounds. Their activity is not hampered by high protein content, and they nurture fibroblast growth at the surface without causing significant hemolysis. In this work, we have generated nanocellulose films with indisputable antimicrobial activity demonstrated using state-of-the-art models that best depict an "in vivo scenario". Our approach is to use fully renewable polymers and find suitable alternatives to silver and cationic antimicrobials. © 2020 American Chemical Society.
- ItemThe innate immune response of self-assembling silk fibroin hydrogels(Cambridge : Royal Soc. of Chemistry, 2021) Gorenkova, Natalia; Maitz, Manfred F.; Böhme, Georg; Alhadrami, Hani A.; Jiffri, Essam H.; Totten, John D.; Werner, Carsten; Carswell, Hilary V. O.; Seib, F. PhilippSilk has a long track record of use in humans, and recent advances in silk fibroin processing have opened up new material formats. However, these new formats and their applications have subsequently created a need to ascertain their biocompatibility. Therefore, the present aim was to quantify the haemocompatibility and inflammatory response of silk fibroin hydrogels. This work demonstrated that self-assembled silk fibroin hydrogels, as one of the most clinically relevant new formats, induced very low blood coagulation and platelet activation but elevated the inflammatory response of human whole blood in vitro. In vivo bioluminescence imaging of neutrophils and macrophages showed an acute, but mild, local inflammatory response which was lower than or similar to that induced by polyethylene glycol, a benchmark material. The time-dependent local immune response in vivo was corroborated by histology, immunofluorescence and murine whole blood analyses. Overall, this study confirms that silk fibroin hydrogels induce a similar immune response to that of PEG hydrogels, while also demonstrating the power of non-invasive bioluminescence imaging for monitoring tissue responses. This journal is
- ItemPreclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model(New York, NY [u.a.] : Hindawi Publ. Corp., 2021) Lotz, Benedict; Bothe, Friederike; Deubel, Anne-Kathrin; Hesse, Eliane; Renz, Yvonne; Werner, Carsten; Schäfer, Simone; Böck, Thomas; Groll, Jürgen; von Rechenberg, Brigitte; Richter, Wiltrud; Hagmann, SebastienReinforced hydrogels represent a promising strategy for tissue engineering of articular cartilage. They can recreate mechanical and biological characteristics of native articular cartilage and promote cartilage regeneration in combination with mesenchymal stromal cells. One of the limitations of in vivo models for testing the outcome of tissue engineering approaches is implant fixation. The high mechanical stress within the knee joint, as well as the concave and convex cartilage surfaces, makes fixation of reinforced hydrogel challenging. Methods. Different fixation methods for full-thickness chondral defects in minipigs such as fibrin glue, BioGlue®, covering, and direct suturing of nonenforced and enforced constructs were compared. Because of insufficient fixation in chondral defects, superficial osteochondral defects in the femoral trochlea, as well as the femoral condyle, were examined using press-fit fixation. Two different hydrogels (starPEG and PAGE) were compared by 3D-micro-CT (μCT) analysis as well as histological analysis. Results. Our results showed fixation of below 50% for all methods in chondral defects. A superficial osteochondral defect of 1 mm depth was necessary for long-term fixation of a polycaprolactone (PCL)-reinforced hydrogel construct. Press-fit fixation seems to be adapted for a reliable fixation of 95% without confounding effects of glue or suture material. Despite the good integration of our constructs, especially in the starPEG group, visible bone lysis was detected in micro-CT analysis. There was no significant difference between the two hydrogels (starPEG and PAGE) and empty control defects regarding regeneration tissue and cell integration. However, in the starPEG group, more cell-containing hydrogel fragments were found within the defect area. Conclusion. Press-fit fixation in a superficial osteochondral defect in the medial trochlear groove of adult minipigs is a promising fixation method for reinforced hydrogels. To avoid bone lysis, future approaches should focus on multilayered constructs recreating the zonal cartilage as well as the calcified cartilage and the subchondral bone plate.
- ItemTreatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs(Basel : Molecular Diversity Preservation International, 2019) Bothe, Friederike; Deubel, Anne-Kathrin; Hesse, Eliane; Lotz, Benedict; Groll, Jürgen; Werner, Carsten; Richter, Wiltrud; Hagmann, SebastienDespite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (_CT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O’Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
- ItemPolymer Hydrogels to Guide Organotypic and Organoid Cultures(Weinheim : Wiley-VCH, 2020) Magno, Valentina; Meinhardt, Andrea; Werner, CarstenHuman organotypic and organoid cultures provide increasingly life-like models of tissue/organ development and disease, enable more realistic drug screening, and may ultimately pave the way for new therapies. A broad variety of extracellular matrix-based or inspired materials is instrumental in these approaches. In this review article, the foundations of the related materials design are summarized with an emphasis on the advantages and limitations of decellularized and reconstituted biopolymeric matrices as well as biohybrid and fully synthetic polymer hydrogel systems applied to enable specific organotypic and organoid cultures. Recent progress in the fabrication of defined hydrogel systems offering thoroughly tunable biochemical and biophysical properties is highlighted. Potentialities of hydrogel-based approaches to address the persisting challenges of organoid technologies, namely scalability, connectivity/integration, reproducibility, parallelization, and in situ monitoring are discussed. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
- ItemDehydroabietylamine-Based Cellulose Nanofibril Films: A New Class of Sustainable Biomaterials for Highly Efficient, Broad-Spectrum Antimicrobial Effects(Washington, DC : ACS Publications, 2019) Hassan, Ghada; Forsman, Nina; Wan, Xing; Keurulainen, Leena; Bimbo, Luis M.; Johansson, Leena-Sisko; Sipari, Nina; Yli-Kauhaluoma, Jari; Zimmermann, Ralf; Stehl, Susanne; Werner, Carsten; Saris, Per E.J.; Österberg, Monika; Moreira, Vânia M.The design of antimicrobial surfaces as integral parts of advanced biomaterials is nowadays a high research priority, as the accumulation of microorganisms on surfaces inflicts substantial costs on the health and industry sectors. At present, there is a growing interest in designing functional materials from polymers abundant in nature, such as cellulose, that combine sustainability with outstanding mechanical properties and economic production. There is also the need to find suitable replacements for antimicrobial silver-based agents due to environmental toxicity and spread of resistance to metal antimicrobials. Herein we report the unprecedented decoration of cellulose nanofibril (CNF) films with dehydroabietylamine 1 (CNF-CMC-1), to give an innovative contact-active surface active against Gram-positive and Gram-negative bacteria including the methicillin-resistant S. aureus MRSA14TK301, with low potential to spread resistance and good biocompatibility, all achieved with low surface coverage. CNF-CMC-1 was particularly effective against S. aureus ATCC12528, causing virtually complete reduction of the total cells from 10 5 colony forming units (CFU)/mL bacterial suspensions, after 24 h of contact. This gentle chemical modification of the surface of CNF fully retained the beneficial properties of the original film, including moisture buffering and strength, relevant in many potential applications. Our originally designed surface represents a new class of ecofriendly biomaterials that optimizes the performance of CNF by adding antimicrobial properties without the need for environmentally toxic silver. © Copyright 2019 American Chemical Society.
- ItemHeparin-based, injectable microcarriers for controlled delivery of interleukin-13 to the brain(Cambridge : Royal Soc. of Chemistry, 2020) Schirmer, Lucas; Hoornaert, Chloé; Le Blon, Debbie; Eigel, Dimitri; Neto, Catia; Gumbleton, Mark; Welzel, Petra B.; Rosser, Anne E.; Werner, Carsten; Ponsaerts, Peter; Newland, BenInterleukin-13 (IL-13) drives cells of myeloid origin towards a more anti-inflammatory phenotype, but delivery to the brain remains problematic. Herein, we show that heparin-based cryogel microcarriers load high amounts of IL-13, releasing it slowly. Intra-striatal injection of loaded microcarriers caused local up-regulation of ARG1 in myeloid cells for pro-regenerative immunomodulation in the brain. © 2020 The Royal Society of Chemistry.
- ItemTuning the Local Availability of VEGF within Glycosaminoglycan-Based Hydrogels to Modulate Vascular Endothelial Cell Morphogenesis(Weinheim : Wiley-VCH, 2020) Limasale, Yanuar Dwi Putra; Atallah, Passant; Werner, Carsten; Freudenberg, Uwe; Zimmermann, RalfIncorporation of sulfated glycosaminoglycans (GAGs) into cell-instructive polymer networks is shown to be instrumental in controlling the diffusivity and activity of growth factors. However, a subtle balance between local retention and release of the factors is needed to effectively direct cell fate decisions. To quantitatively unravel material characteristics governing these key features, the GAG content and the GAG sulfation pattern of star-shaped poly(ethylene glycol) (starPEG)–GAG hydrogels are herein tuned to control the local availability and bioactivity of GAG-affine vascular endothelial growth factor (VEGF165). Hydrogels containing varying concentrations of heparin or heparin derivatives with different sulfation pattern are prepared and thoroughly characterized for swelling, mechanical properties, and growth factor transport. Mathematical models are developed to predict the local concentration and spatial distribution of free and bound VEGF165 within the gel matrices. The results of simulation and experimental studies concordantly reveal how the GAG concentration and sulfation pattern determine the local availability of VEGF165 within the cell-instructive hydrogels and how the factor—in interplay with cell-instructive gel properties—determines the formation and spatial organization of capillary networks of embedded human vascular endothelial cells. Taken together, this study exemplifies how mathematical modeling and rational hydrogel design can be combined to pave the way for precision tissue engineering. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim