Development and evaluation of a sequential-release hydrogel loaded emodin and shikonin for chronic refractory wound therapy

Objectives Chronic refractory wounds are characterized by persistent inflammation and bacterial colonization. This study aims to develop a sequential-release hydrogel incorporating emodin (EMO) and shikonin (SKN) to provide coordinated antibacterial and anti-inflammatory effects tailored to the wound-healing process. Methods A dynamic hydrogel was fabricated via Schiff base crosslinking between chlorogenic acid-grafted chitosan and oxidized Bletilla striata polysaccharide. EMO alkaline solution and SKN-loaded nanostructured lipid carriers were incorporated. The release profiles were evaluated in vitro. Antibacterial activity was assessed using the inhibition zone assay, and anti-inflammatory activity was determined by LPS-induced NO release assay. Skin irritation was tested using an impaired skin model, and wound-healing efficacy was evaluated in a diabetic rat model. Key findings SKN exhibited a consistently slower release rate than EMO, confirming the sequential release profile. The drug-loaded hydrogel demonstrated significant antibacterial and anti-inflammatory activities in vitro without causing skin irritation. In diabetic wound rats, the hydrogel markedly accelerated wound closure, reduced inflammatory infiltration, and promoted tissue regeneration compared with free drug treatment. Conclusions The sequential-release hydrogel loaded with EMO and SKN represents a promising therapeutic strategy for chronic refractory wounds by providing spatially and temporally controlled antibacterial and anti-inflammatory effects.