Mechanically-reinforced and highly adhesive decellularized tissue-derived hydrogel for efficient tissue repair

Abstract

Hydrogels derived from decellularized tissue (DT) have demonstrated huge potential in regenerative medicine. However, the hydrogel resulting from a thermally-induced crosslinking process via the self-assembly of collagen fibrils in DT exhibits weak mechanical properties. This restricts its application in tissue regeneration that requires strong mechanical properties and structural integrity of the hydrogel constructs. To overcome the aforementioned challenges of the present DT-derived hydrogels, we developed a DT hydrogel equipped with oxidative crosslinking chemistry by conjugating catechol moieties to the extracellular matrix in DT. The catechol-modified DT (DT-CA) constructed hydrogel instantly upon oxidation via catechol–catechol adducts, exhibiting 10 times stronger mechanical properties compared to that of the unmodified DT hydrogel. The oxidative crosslinking also increased the adhesiveness and physical integrity of the DT hydrogel, allowing for the shaping of scaffolds without using any supportive material, which could not be accomplished with conventional DT hydrogels. DT-CA hydrogel demonstrated an enhanced osteogenic differentiation of human stem cells and accelerated formation of new bones in a mouse model of the critical-sized calvarial defect. In addition, the patch type of DT-CA facilitated wound healing by mediating efficient topical delivery of growth factors. Similarly, other phenolic adhesive moiety (pyrogallol) could be introduced to improve DT hydrogel for promoting wound regeneration. Collectively, the results of this study support the applicability of mechanically-reinforced, adhesive DT hydrogel for effective tissue regeneration.