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.

Automated summary

A novel hydrogel system was developed for the treatment of chronic diabetic wounds, which showed the ability to shorten the inflammatory stage and promote angiogenesis. Both in vitro and in vivo experiments demonstrated excellent biocompatibility and therapeutic potential of the prepared hydrogel.