Degradable Microneedle Patch Loaded with Doxycycline Hydrochloride and Vascular Endothelial Growth Factors for Promoting Diabetic Wound Healing

Abstract

Difficult-to-heal skin wounds are serious complications of diabetes. Microneedles (MNs) are a new type of physically penetrating wound dressing that can synergistically carry drugs. In this study, good biocompatible gelatin methacrylate (Gelma) and polyvinyl alcohol (PVA), loading with doxycycline hydrochloride (DH) and vascular endothelial growth factors (VEGF) are used to prepare the DH/VEGF@Gelma-MNs. Gelma-MNs possess well-aligned conical structures, good mechanical, and swelling properties, and could penetrate the skin. DH/VEGF@Gelma-MNs show biocompatibility and antibacterial ability to inhibit the growth of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Besides, DH/VEGF@Gelma-MNs significantly promote the migration and tube formation of human umbilical vein endothelial cells (HUVECs). DH/VEGF@Gelma-PNs treatment accelerates diabetic wound closure in vivo compared to DH/VEGF@Gelma-plain patch (DH/VEGF@Gelma-PPs) flat patch and DH/VEGF solution injection. Histological evaluation shows that DH/VEGF@Gelma-MNs coverage presents intact wound re-epithelialization, follicle and sebaceous gland formation, more collagen deposition and remodeling, and angiogenesis. In conclusion, DH/VEGF@Gelma-MNs exert antimicrobial and angiogenic effects by releasing DH and VEGF to promote diabetic wound healing, posing an intriguing strategy based on a synergistic MN therapeutic platform.