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Covalent linkage of sulfated hyaluronan to the collagen scaffold Mucograft® enhances scaffold stability and reduces proinflammatory macrophage activation in vivo

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Bioactive Materials 2022年第2期7卷 420-434页

作者： sarah al-maawi Sandra Rother Norbert Halfter Karen M.Fiebig Juliane Moritz Stephanie Moeller Matthias Schnabelrauch Charles James Kirkpatrick Robert Sader Hans-Peter Wiesmann Dieter Scharnweber Vera Hintze Shahram Ghanaati Clinic for Maxillofacial and Plastic Surgery Goethe UniversityFrankfurt Am MainGermany Institute of Materials Science Max Bergmann Center of BiomaterialsTU DresdenBudapester Str.2701069DresdenGermany Biomaterials Department INNOVENT e.V.Prüssingstr.27B07745JenaGermany Department of Cellular and Molecular Medicine Glycobiology Research and Training CenterUniversity of CaliforniaSan DiegoLa JollaCAUSA

Sulfated glycosaminoglycans(sGAG)show interaction with biological mediator *** collagen-based biomaterials are widely used in clinics,their combination with high-sulfated hyaluronan(sHA3)is *** study aims to functionalize a collagen-based scaffold(Mucograft®)with sHA3 via electrostatic(sHA3/PBS)or covalent binding to collagen fibrils(sHA3+EDC/NHS).Crosslinking without sHA3 was used as a control(EDC/NHS Ctrl).The properties of the sHA3-functionalized materials were *** vitro growth factor and cytokine release after culturing with liquid platelet-rich fibrin was performed by means of *** cellular reaction to the biomaterials was analyzed in a subcutaneous rat *** study revealed that covalent linking of sHA3 to collagen allowed only a marginal release of sHA3 over 28 days in contrast to electrostatically bound ***3+EDC/NHS scaffolds showed reduced vascular endothelial growth factor(VEGF),transforming growth factor beta 1(TGF-β1)and enhanced interleukin-8(IL-8)and epithelial growth factor(EGF)release in vitro compared to the other *** sHA3/PBS and EDC/NHS Ctrl scaffolds showed a high proinflammatory reaction(M1:CD-68+/CCR7+)and induced multinucleated giant cell(MNGC)formation in *** sHA3+EDC/NHS scaffolds reduced the proinflammatory macrophage M1 response and did not induce MNGC formation during the 30 ***3+EDC/NHS scaffolds had a stable structure in vivo and showed sufficient integration into the implantation region after 30 days,whereas EDC/NHS Ctrl scaffolds underwent marked disintegration and lost their initial *** summary,functionalized collagen(sHA3+EDC/NHS)modulates the inflammatory response and is a promising biomaterial as a stable scaffold for full-thickness skin regeneration in the future.

关键词： Sulfated hyaluronan Collagen Wound healing Cellular reaction Multinucleated giant cells

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