Promote anti-inflammatory and angiogenesis using a hyaluronic acid-based hydrogel with miRNA-laden nanoparticles for chronic diabetic wound treatment

Chronic diabetic wound causes serious threat to human health due to its long inflammatory phase and the reduced vascularization. Herein, we develop a hydrogel system for the treatment of diabetic wound, which can short the inflammatory stage (through the use of ori) and promote the angiogenesis (through the addition of siRNA-29a gene). Based on the Schiff base bonds, the Gel/Alg@ori/HA-PEI@siRNA-29a hydrogel was prepared by mixing oxidized hydroxymethyl propyl cellulose (OHMPC), adipic dihydrazide-modified hyaluronic acid (HA-ADH), oridonin (ori) loaded alginate microspheres (Alg@ori) and siRNA-29a gene-loading hyaluronic acid-polyethyleneimine complex HA-PEI@siRNA-29a (HA-PEI@siRNA-29a) under physiological conditions, which had moderate mechanical strength, appropriate swelling property, impressive stability, and slow release ability of ori and siRNA-29a. Excellent biocompatibility of the prepared hydrogel was also confirmed by in vitro mouse fibroblasts L929 cells culture study. Moreover, in vivo experiments further demonstrated that the prepared Gel/Alg@ori/HA-PEI@siRNA-29a hydrogel not only significantly accelerated the diabetic wound healing, angiogenesis factors (alpha-SMA and CD31 ) production, but also inhibited pro-inflammatory factors (IL-6 and TNF-alpha). In summary, we believe that the prepared hydrogels exhibit great potential for the treatment of chronic diabetic wound. (C) 2020 Published by Elsevier B.V.