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    A Versatile Macromer-Based Glycosaminoglycan (sHA3) Decorated Biomaterial for Pro-Osteogenic Scavenging of Wnt Antagonists
    (Basel : MDPI, 2020) Gronbach, Mathis; Mitrach, Franziska; Möller, Stephanie; Rother, Sandra; Friebe, Sabrina; Mayr, Stefan G.; Schnabelrauch, Matthias; Hintze, Vera; Hacker, Michael C.; Schulz-Siegmund, Michaela
    High serum levels of Wnt antagonists are known to be involved in delayed bone defect healing. Pharmaceutically active implant materials that can modulate the micromilieu of bone defects with regard to Wnt antagonists are therefore considered promising to support defect regeneration. In this study, we show the versatility of a macromer based biomaterial platform to systematically optimize covalent surface decoration with high-sulfated glycosaminoglycans (sHA3) for efficient scavenging of Wnt antagonist sclerostin. Film surfaces representing scaffold implants were cross-copolymerized from three-armed biodegradable macromers and glycidylmethacrylate and covalently decorated with various polyetheramine linkers. The impact of linker properties (size, branching) and density on sHA3 functionalization efficiency and scavenging capacities for sclerostin was tested. The copolymerized 2D system allowed for finding an optimal, cytocompatible formulation for sHA3 functionalization. On these optimized sHA3 decorated films, we showed efficient scavenging of Wnt antagonists DKK1 and sclerostin, whereas Wnt agonist Wnt3a remained in the medium of differentiating SaOS-2 and hMSC. Consequently, qualitative and quantitative analysis of hydroxyapatite staining as a measure for osteogenic differentiation revealed superior mineralization on sHA3 materials. In conclusion, we showed how our versatile material platform enables us to efficiently scavenge and inactivate Wnt antagonists from the osteogenic micromilieu. We consider this a promising approach to reduce the negative effects of Wnt antagonists in regeneration of bone defects via sHA3 decorated macromer based macroporous implants. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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    EndOxy: Dynamic Long-Term Evaluation of Endothelialized Gas Exchange Membranes for a Biohybrid Lung
    (Weinheim : Wiley-VCH, 2020) Klein, Sarah; Hesselmann, Felix; Djeljadini, Suzana; Berger, Tanja; Thiebes, Anja Lena; Schmitz-Rode, Thomas; Jockenhoevel, Stefan; Cornelissen, Christian G.
    In the concept of a biohybrid lung, endothelial cells seeded on gas exchange membranes form a non-thrombogenic an anti-inflammatory surface to overcome the lacking hemocompatibility of today’s oxygenators during extracorporeal membrane oxygenation. To evaluate this concept, the long-term stability and gas exchange performance of endothelialized RGD-conjugated polydimethylsiloxane (RGD-PDMS) membranes was evaluated. Human umbilical vein endothelial cells (ECs) were cultured on RGD-PDMS in a model system under physiological wall shear stress (WSS) of 0.5 Pa for up to 33 days. Gas exchange performance was tested with three biological replicates under elevated WSS of 2.5 Pa using porcine blood adjusted to venous values following ISO 7199 and blood gas analysis. EC morphology was assessed by immunocytochemistry (n = 3). RGD-PDMS promoted endothelialization and stability of endothelialized membranes was shown for at least 33 days and for a maximal WSS of 2.5 Pa. Short-term exposure to porcine blood did not affect EC integrity. The gas transfer tests provided evidence for the oxygenation and decarboxylation of the blood across endothelialized membranes with a decrease of transfer rates over time that needs to be addressed in further studies with larger sample sizes. Our results demonstrate the general suitability of RGD-PDMS for biohybrid lung applications, which might enable long-term support of patients with chronic lung failure in the future. © 2019, The Author(s).
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    In vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams
    (Berlin ; Heidelberg : Springer, 2022) Kokozidou, Maria; Gögele, Clemens; Pirrung, Felix; Hammer, Niels; Werner, Christian; Kohl, Benjamin; Hahn, Judith; Breier, Annette; Schröpfer, Michaela; Meyer, Michael; Schulze-Tanzil, Gundula
    Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-epsilon-caprolactone) (P(LA-CL)) / polylactic acid (PLA) constructs using a dynamic nude mice xenograft model. (P(LA-CL))/PLA scaffolds remained either untreated (co) or were functionalized by gas fluorination (F), collagen foam cross-linked with hexamethylene diisocyanate (HMDI) (coll), or F combined with the foam (F+coll). Cell-free constructs or those seeded for 1 week with lapine ACL ligamentocytes were implanted into nude mice for 12 weeks. Following explantation, cell vitality and content, histo(patho)logy of scaffolds (including organs: liver, kidney, spleen), sulphated glycosaminoglycan (sGAG) contents and biomechanical properties were assessed. Scaffolds did not affect mice weight development and organs, indicating no organ toxicity. Moreover, scaffolds maintained their size and shape and reflected a high cell viability prior to and following implantation. Coll or F+coll scaffolds seeded with cells yielded superior macroscopic properties compared to the controls. Mild signs of inflammation (foreign-body giant cells and hyperemia) were limited to scaffolds without collagen. Microscopical score values and sGAG content did not differ significantly. Although remaining stable after explantation, elastic modulus, maximum force, tensile strength and strain at F-max were significantly lower in explanted scaffolds compared to those before implantation, with no significant differences between scaffold subtypes, except for a higher maximum force in F+coll compared with F samples (in vivo). Scaffold functionalization with fluorinated collagen foam provides a promising approach for ACL tissue engineering.
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    In vitro pre-vascularisation of tissue-engineered constructs A co-culture perspective
    (London : BioMed Central, 2014) Baldwin, J.; Antille, M.; Bonda, U.; De-Juan-Pardo, E.M.; Khosrotehrani, K.; Ivanovski, S.; Petcu, E.B.; Hutmacher, D.W.
    In vitro pre-vascularization is one of the main vascularization strategies in the tissue engineering field. Culturing cells within a tissue-engineered construct (TEC) prior to implantation provides researchers with a greater degree of control over the fate of the cells. However, balancing the diverse range of different cell culture parameters in vitro is seldom easy and in most cases, especially in highly vascularized tissues, more than one cell type will reside within the cell culture system. Culturing multiple cell types in the same construct presents its own unique challenges and pitfalls. The following review examines endothelial-driven vascularization and evaluates the direct and indirect role other cell types have in vessel and capillary formation. The article then analyses the different parameters researchers can modulate in a co-culture system in order to design optimal tissue-engineered constructs to match desired clinical applications.