Chen Yanzheng, Wang Qing, Ning Fangrui, Du Chang, Chen Mingsheng, Feng Chuanliang, Dong Chang-Ming
School of Chemistry and Chemical Engineering, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
Department of Stomatology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, P. R. China.
ACS Appl Mater Interfaces. 2024 Dec 25;16(51):70256-70273. doi: 10.1021/acsami.4c15674. Epub 2024 Dec 13.
Despite the great progress of various multifunctional wound dressings, it is challenging to simultaneously achieve complete healing and functional remodeling for diabetic foot ulcers and refractory chronic wounds. Aiming to comprehensively regulate chronic inflammation, angiogenesis, and metabolism processes, herein, a novel kind of dynamic hyaluronic acid (HA) hydrogel was designed by combining boronate and coordination chemistry. Besides having injectability, self-healing, and detachment properties, dynamic HA hydrogels presented diabetic wound-responsive degradation and controllable HS release. They could efficiently polarize M1-to-M2 polarization and regulate inflammatory cytokine secretion and multiple inflammation-related mRNA expressions through cooperative actions of reactive oxygen species elimination + HS release + Zn regulation, thus driving chronic inflammation into the proliferation and remodeling stages. Moreover, the screened lead hydrogel HTZS could regulate angiogenesis-related signaling pathways and metabolism processes to promote neovascularization and mature vessel formation, re-epithelization, high-level collagen-I deposition, and dense hair follicle regeneration, achieving complete healing and functional remodeling in diabetic wounds. Importantly, this work opens a new avenue to design dynamic biopolymer hydrogels for high-performance wound dressing and decipher the key role of multiple orchestrated regulations of inflammation-angiogenesis-metabolism on complete healing and functional remodeling in chronic and diabetic wounds.
尽管各种多功能伤口敷料取得了巨大进展，但要同时实现糖尿病足溃疡和难治性慢性伤口的完全愈合和功能重塑仍具有挑战性。为了全面调节慢性炎症、血管生成和代谢过程，在此，通过结合硼酸酯和配位化学设计了一种新型的动态透明质酸（HA）水凝胶。动态HA水凝胶除了具有可注射性、自愈性和可分离性外，还表现出糖尿病伤口响应性降解和可控的HS释放。它们可以通过活性氧消除+HS释放+锌调节的协同作用，有效地将M1极化转变为M2极化，并调节炎症细胞因子分泌和多种炎症相关mRNA表达，从而将慢性炎症驱动到增殖和重塑阶段。此外，筛选出的先导水凝胶HTZS可以调节血管生成相关信号通路和代谢过程，以促进新血管形成和成熟血管形成、再上皮化、高水平I型胶原蛋白沉积和密集毛囊再生，实现糖尿病伤口的完全愈合和功能重塑。重要的是，这项工作为设计用于高性能伤口敷料的动态生物聚合物水凝胶开辟了一条新途径，并揭示了炎症-血管生成-代谢的多重协同调节在慢性和糖尿病伤口完全愈合和功能重塑中的关键作用。
