Sr-MOF-based hydrogel promotes diabetic tissue regeneration through simultaneous antimicrobial and antiinflammatory properties

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.