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.

来自脱细胞组织 (DT) 的水凝胶在再生医学中显示出巨大的潜力。然而，由热诱导交联过程产生的水凝胶通过 DT 中胶原纤维的自组装表现出弱的机械性能。这限制了其在需要水凝胶结构的强机械性能和结构完整性的组织再生中的应用。为了克服现有 DT 衍生水凝胶的上述挑战，我们通过将儿茶酚部分与 DT 中的细胞外基质结合，开发了一种配备氧化交联化学的 DT 水凝胶。儿茶酚修饰的 DT (DT-CA) 在通过儿茶酚-儿茶酚加合物氧化后立即构建水凝胶，与未修饰的 DT 水凝胶相比，其机械性能强 10 倍。氧化交联还增加了 DT 水凝胶的粘附性和物理完整性，允许在不使用任何支撑材料的情况下成型支架，这是传统 DT 水凝胶无法实现的。DT-CA 水凝胶证明了人类干细胞的成骨分化增强，并在临界尺寸颅骨缺损的小鼠模型中加速了新骨的形成。此外，DT-CA 的贴片类型通过介导生长因子的有效局部递送来促进伤口愈合。类似地，可以引入其他酚类粘合剂部分（邻苯三酚）来改善 DT 水凝胶以促进伤口再生。总的来说，这项研究的结果支持机械增强的粘性 DT 水凝胶在有效组织再生中的适用性。