Functional hyaluronic acid/gelatin hydrogel accelerates the closure and healing of diabetic wounds

The healing of extensive drug-resistant and skin area diabetic wounds poses significantly greater challenges compared to the recovery of typical wounds. Advanced approaches like tissue engineering and regenerative medicine hold promise, exemplified by hyaluronic acid/gelatin/poly(N-isopropyl acrylamide) (PNIPAm) hydrogel, a temperature-sensitive auto-shrinkage hydrogel with injectable biomimetic mechanical functions. Here, aldehyde-modified hyaluronic acid (HA-CHO) and hydrazide-grafted gelatin (Gel-ADH) are chosen, crosslinked to form a gel by the Schiff base reaction, introduced with PNIPAm to accelerate the wound contraction, and loaded with the pro-angiogenic peptide Ten-2 and the antimicrobial peptides IB-367. Both in vitro and in vivo studies illustrate their effectiveness in accelerating and facilitating the healing process of skin wounds. The hydrogel is able to consistently and successfully suppress the growth of bacteria in the wound, and upregulate the expression of pro-inflammatory factors TGF-β1, α-SMA, and p-Smad2, all of which could aid in the healing process of diabetic wounds. This injectable hydrogel containing antimicrobial peptides and accelerating wound healing mimics the contractile characteristics of myofibroblasts through its biomimetic mechanical mechanism. It can adapt to the dynamic changes of the skin and help repair diabetic wounds that are challenging to treat and may prove to be a good option for regenerative medicine.