An EGCG-enhanced pH/ROS dual-responsive hyaluronic acid hydrogel loaded with ginseng-derived exosomes for diabetic oral ulcers treatment

Oral ulcers (OU) are prone to recurrence, and are often manifested by the accompanying bacterial infections which may induce a vicious cycle of oxidative stress and inflammatory responses. Traditional treatment methods have limited effects, including being eliminated in the moist and dynamic environment of the mouth, and are prone to various side effects or the development of drug resistance. In this study, we designed borate ester-based and Schiff base-cross-linked hydrogel (OPEC), and loaded ginseng-derived exosome (GEX@OPEC) for the treatment of OU. OPEC hydrogel is composed of phenylboronic acid-functionalized hyaluronic acid oxide (OHA-PBA), epigallocatechin gallate (EGCG), and carboxymethyl chitosan (CMCS). The addition of EGCG enhances its borate cross-linking network and improves the adhesion of the hydrogel. GEX is connected to OPEC through hydrogen bonds and loaded into the hydrogel, further enhancing its gel network. GEX@OPEC exhibited excellent biocompatibility and degradability, ensuring safe oral use of the hydrogel. GEX@OPEC can release EGCG and GEX in response to pH and ROS to exert therapeutic effects. Our research results showed that GEX@OPEC had excellent antibacterial properties, anti-inflammatory and antioxidant stress effects, as well as angiogenic properties, which can effectively promote the healing of OU in diabetic rat models simulating OU. To sum up, GEX@OPEC has good application prospects in the treatment of diabetic OU.