Zhang Fan, Zhang Haijuan, Wang Shengfu, Gao Mingying, Du Kaiyi, Chen Xinyuan, Lu Yang, Hu Qianqian, Du Anyu, Du Shenghu, Wang Jian, Shi Keqing, Chen Zimiao, Li Zhuo, Li Zhenglin, Xiao Jian
Department of Wound healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Nat Commun. 2025 Apr 20;16(1):3738. doi: 10.1038/s41467-025-58987-w.
Achieving rapid and scar-free wound repair is a key goal in the field of regenerative medicine. Herein, a dynamically Schiff base-crosslinked hydrogel (F/R gel) with phase-adaptive regulating functions is constructed to integratedly promote rapid re-epithelization with suppressed scars on chronic infected wounds. Specifically, the gel effectively eliminates multidrug-resistant bacterial biofilm at infection stage via antimicrobial activity of ε-polylysine firstly dissociated from hydrogel matrix in infectious microenvironment, and interrupts the severe oxidative stress-inflammation cycle at wound site by the released ceria nanozyme, thus stimulating a pro-regenerative environment to ensure tissue repair. Subsequently, fibroblast growth factor/c-Jun siRNA co-loaded microcapsules gradually disintegrate to release drugs, facilitating neoangiogenesis and cell proliferation but simultaneously blocking c-Jun overexpression for fibrotic scar suppression. Notably, the F/R gel facilitates normal-like skin regeneration with no perceptible scars formed on infected male mouse wound and female rabbit ear wound models. Our work offers a promising regenerative strategy emphasizing immunomodulatory and fibroblast subtype modulation for scarless wound repair.
实现快速且无疤痕的伤口修复是再生医学领域的一个关键目标。在此，构建了一种具有相适应调节功能的动态席夫碱交联水凝胶（F/R凝胶），以综合促进慢性感染伤口的快速重新上皮化并抑制疤痕形成。具体而言，该凝胶首先通过在感染微环境中从水凝胶基质解离的ε-聚赖氨酸的抗菌活性，在感染阶段有效消除多重耐药细菌生物膜，并通过释放的二氧化铈纳米酶中断伤口部位严重的氧化应激-炎症循环，从而刺激促再生环境以确保组织修复。随后，共负载成纤维细胞生长因子/c-Jun小干扰RNA的微胶囊逐渐分解以释放药物，促进新血管生成和细胞增殖，但同时阻断c-Jun的过度表达以抑制纤维化疤痕。值得注意的是，F/R凝胶促进了类似正常皮肤的再生，在感染的雄性小鼠伤口和雌性兔耳伤口模型上未形成明显的疤痕。我们的工作提供了一种有前景的再生策略，强调免疫调节和成纤维细胞亚型调节以实现无疤痕伤口修复。
