Immunoregulatory hydrogel decorated with Tannic acid/Ferric ion accelerates diabetic wound healing via regulating Macrophage polarization

Diabetic wound management still faces great challenges mainly due to immune disorders at wound area. Especially, macrophage polarization toward M2 phenotype is severely inhibited at the inflammatory stage. Thus, targeted regulation of macrophage polarization could be a useful approach to normalize the immune environment of diabetic wound to accelerate wound healing. Herein, a composited hydrogel derived from natural polymers, as an immunoregulatory dressing, was fabricated to treat diabetic wound. The composited hydrogel (GBTF) was synthesized by one step photo-polymerization of gelatin methacrylate (GelMA), Bletilla Striata polysaccharide (BSP) and tannic acid/ferric iron complex (TA/Fe3+). Attributed to the chemical and physical cross-linking, the GBTF hydrogel exhibited adequate mechanical properties. Thanks to the photothermal transition of TA/Fe3+ in GBTF, good antibacterial capacity was achieved. Meanwhile, the polyphenol in TA could help to attenuate excessive ROS and induce macrophage polarization toward M2 phenotype. Furthermore, the potential immunoregulatory mechanism of the GBTF hydrogel was investigated through RNA sequencing in vitro. In addition, BSP showed positive contribution in vascularization. In vivo, results from diabetic wound model showed that the wound treated by GBTF hydrogel presented the fastest closure rate, superior granulation tissue regeneration, re-epithelialization and collagen deposition. These results indicated GBTF hydrogel rapidly promoted wound healing through anti-inflammation and pro-angiogenesis. The GBTF hydrogel showed great potential to serve as promising dressing for treatment of diabetic wounds in clinic.