A carrier-free, dual-functional hydrogel constructed of antimicrobial peptide Jelleine-1 and 8Br-cAMP for MRSA infected diabetic wound healing

Abstract

Bacterial infection and local growth factor deficiency are two of the major causes of the nonunion of diabetic wounds. Antimicrobial peptides (AMPs) are believed to be alternatives to antibiotics against drug-resistant bacterial infections. 8-Bromoadenosine-3', 5'-cyclic monophosphate (8Br-cAMP) can promote cells to secrete growth factors and accelerate cell proliferation. In the present study, we constructed a hydrogel with antimicrobial peptide Jelleine-1 (J-1) and 8Br-cAMP without any other gelators or chemical crosslinking agents. The hydrogel was proved to promote the secretion of transforming growth factor-β (TGF-β) and vascular endothelial growth factor-A (VEGFA) in vitro and in vivo. Notably, it exhibited potent potential for wound healing in methicillin-resistant Staphylococcus aureus (MRSA) infected diabetic wounds. This would be attributed to the retention of AMPs and 8Br-cAMP on the wound site by the hydrogel system. In addition, the hydrogel also showed good biodegradability, proper stability, and good biocompatibility. This study would shed light on the development of carrier-free and multifunctional hydrogel for wound healing. STATEMENT OF SIGNIFICANCE: Bacterial infection and local growth factor deficiency are two of the major causes for the nonunion of refractory wounds. In the present study, an injectable carrier-free hydrogel was constructed of a natural antimicrobial peptide J-1 and 8Br-cAMP by eco-friendly physical crosslinking without any other gelators or chemical crosslinking agents. The hydrogel exhibited excellent antimicrobial activity and was proved to promote the secretion of TGF-β and VEGFA in vitro and in vivo. Correspondingly, the hydrogel showed exceptionally wound healing effects in the wound model of MRSA infected diabetic rats. This study would provide an alternative strategy or a potential hydrogel dressing for the treatment of chronic or refractory wounds.

Keywords: 8Br-cAMP; Antimicrobial peptides J-1; Biocompatibility; Diabetic wounds; Hydrogel.