Novel silver and nanoparticle-encapsulated growth factor co-loaded chitosan composite hydrogel with sustained antimicrobility and promoted biological properties for diabetic wound healing

Diabetic foot ulcer, one of the most common diabetic complications, is a progressive wound occurred on the skin with irregularly delayed wound healing rate due to impaired metabolism and weak immune responses. Such chronic wound remains a serious healthcare burden to the diabetics since it is often associated with high risk of limb loss due to amputation and leads to a reduced survival consequently. To improve the efficiency of diabetic wound healing, a synthetic chitosan-based composite hydrogel named SNPECHG incorporating silver ions (Ag+) and nanoparticle-encapsulated epidermal growth factor (EGF) was developed in this study. The optimal effective dosages of 24-mM Ag+ and 60-μg mL−1 EGF for the SNPECHG manufacture were first determined based on the results of antibacterial, cytotoxicity, and cell growth examinations. We then characterized the optimized SNPECHG and found that the composite hydrogel was able to provide sustained release of Ag+ and EGF, and exhibited a significantly higher hydration capacities, including the swelling degree and equilibrium water content, in PBS than those in deionized water, showing that the developed SNPECHG is highly applicable in the ion-rich environment such as chronic wound site. According to the results of in vivo study using diabetic rats, the one with SNPECHG exhibited a markedly enhanced wound healing effect compared with the other settings since day 3, and may reach a degree of wound closure of 97% at day 14 that was 7.4% (P < 0.05) and 18.9% (P < 0.05) higher than the values gained from the groups with the commercial dressing HeraDerm and gauze, respectively. Moreover, the wound treated with the SNPECHG exhibited thorough re-epithelization, sufficient collagen deposition, and accelerated collagen maturation confirmed by the histological analysis. Taken all together, we anticipate that the SNPECHG is highly advantageous for use in the clinical diabetic/chronic wound treatment.