Zhang Siming, Ge Gaoran, Li Wenhao, Dong Jiale, Hu Xianli, Qin Yi, Zhang Peng, Bai Jiaxiang, Zhang Weiwei, Su Zheng, Geng Dechun, Zhu Chen
Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
Department of Orthopedics, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.
Mater Today Bio. 2025 May 28;32:101906. doi: 10.1016/j.mtbio.2025.101906. eCollection 2025 Jun.
Severe tissue dysfunction in diabetic patients has been a challenging clinical problem. Both bacterial infections and chronic inflammation contribute to diabetic microenvironmental disorders and poor tissue regeneration. In this paper, a composite hydrogel (Gelma@Sr-ZIF-8) was prepared by incorporating a strontium (Sr)-doped metal-organic framework (Sr-ZIF-8) into Gelatin methacryloyl (Gelma) hydrogel, which could reverse diabetic microenvironmental disorders and promote tissue regeneration in diabetic wounds. The zinc ions released from this hydrogel directly killed invading planktonic bacteria and inhibited biofilm formation. Moreover, zinc ions can disrupt biofilm structure, penetrate bacteria and remove biofilm. In addition, strontium and zinc ions reversed the pro-inflammatory immune microenvironment by modulating redox balance, restored phagocytosis by macrophages, and killed bacteria released from mature biofilms. In addition, strontium ions promote the proliferation and differentiation of osteoblasts, inhibit the activity of osteoclasts, and promote the regeneration of blood vessels at the site of bone defects, ultimately promoting the regeneration of diabetic tissue. The synergistic effect of zinc and strontium ions gives Gelma@Sr-ZIF-8 excellent full-stage antibacterial and immunomodulatory properties. In vitro and in vivo studies have shown that Gelma@Sr-ZIF-8 can remodel the disturbed diabetic microenvironment, ultimately improving the efficacy of antimicrobial therapy and promoting diabetic tissue regeneration.
糖尿病患者的严重组织功能障碍一直是一个具有挑战性的临床问题。细菌感染和慢性炎症都会导致糖尿病微环境紊乱和组织再生不良。在本文中，通过将锶（Sr）掺杂的金属有机框架（Sr-ZIF-8）掺入甲基丙烯酰化明胶（Gelma）水凝胶中制备了一种复合水凝胶（Gelma@Sr-ZIF-8），其可以逆转糖尿病微环境紊乱并促进糖尿病伤口的组织再生。从这种水凝胶中释放的锌离子直接杀死入侵的浮游细菌并抑制生物膜形成。此外，锌离子可以破坏生物膜结构，穿透细菌并去除生物膜。此外，锶离子和锌离子通过调节氧化还原平衡逆转促炎免疫微环境，恢复巨噬细胞的吞噬作用，并杀死从成熟生物膜释放的细菌。此外，锶离子促进成骨细胞的增殖和分化，抑制破骨细胞的活性，并促进骨缺损部位的血管再生，最终促进糖尿病组织的再生。锌离子和锶离子的协同作用赋予Gelma@Sr-ZIF-8优异的全阶段抗菌和免疫调节特性。体外和体内研究表明，Gelma@Sr-ZIF-8可以重塑紊乱的糖尿病微环境，最终提高抗菌治疗的疗效并促进糖尿病组织再生。
