Feasibility Study of Tissue Transglutaminase for Self-CatalyticCross-Linking of Self-Assembled Collagen Fibril Hydrogel and Its PromisingApplication in Wound Healing Promotion

摘要

Collagen-based bio-hydrogels are undoubtedly a hot spot in the development of biological dressings for wound healing promotion. Herein, glutamine transaminase (TGase), a biological nontoxic cross-linker with high specific activity and reaction rate under mild conditions, was utilized for the self-catalytic cross-linking of the regenerated collagen (COL) fibril hydrogel fabricated through a molecular self-assembly method. The results showed that the natural triple helical conformation of COL remained completely integrated after self-catalytic cross-linking TGase, which was definitively the fundamental for maintaining its superior bioactivity. It was worth noting that TGase could promote the self-assembly process of COL building blocks into a higher order D-period cross-striated structure. Also, the reconstructed TGase cross-linked COL fibrils exhibited a higher degree of interfiber entanglements with more straight and longer fibrils. Meanwhile, the thermal stability of COL was significantly improved after introducing TGase. Besides, the cytocompatibility analysis suggested that the regenerated COLfibril hydrogel showed excellent cell growth activity and proliferationability when the dosage of TGase is less than 40 U/g. Further, animalexperiments indicated that the targeted COL fibril hydrogel couldsignificantly promote skin wound healing, exhibiting better capacityof skin tissue for regeneration than the COL hydrogel untreated asexpected. Therefore, the reconstructed TGase cross-linked COL fibrilhydrogel could serve as a novel soft material for wound healing promotion.