Antibacterial adhesive self-healing hydrogels to promote diabetic wound healing

Abstract

The development of compressible, stretchable and self-healing hydrogel dressings with good adhesive, antibacterial and angiogenesis properties is needed to promote the regeneration of diabetic wounds in clinical applications. In this work, a series of self-healing, adhesive and antibacterial hydrogels based on gelatin methacrylate (GelMA), adenine acrylate (AA), and CuCl₂ were designed through covalent bonding, coordination complexation of Cu²⁺ and carboxyl groups and hydrogen bonding to promote diabetic wound healing. These hydrogels exhibit efficient self-healing properties, remarkable fatigue resistance, and good adhesive properties due to the hydrogen bond and the metal-ligand coordination provided by the Cu²⁺ and the carboxyl group. The GelMA/AA/Cu1.0 hydrogel (containing 1.0 mg/mL Cu²⁺) with well-balanced biocompatibility and antibacterial properties exhibited efficient hemostatic performance in a mouse liver trauma model and significantly promoted the healing process in a full-thickness skin diabetic wound model. The immunohistochemistry results showed that the GelMA/AA/Cu1.0 hydrogel can promote regular epithelialization and collagen deposition when compared to the Tegaderm^TM Film, GelMA hydrogel, and GelMA/AA/Cu0 hydrogel. The immunofluorescence results confirmed that the GelMA/AA/Cu1.0 hydrogel can reduce the expression of proinflammatory factors and promote angiogenesis. In conclusion, the GelMA/AA/Cu hydrogel is an effective wound dressing to promote the healing process of diabetic skin wounds. STATEMENT OF SIGNIFICANCE: Diabetic wounds exhibit an extremely high risk of bacterial infection and poor angiogenesis in a high-sugar environment, hindering their healing process. Hydrogel wound dressings are a promising wound care material that need to have stable and long-lasting adhesive properties, avoid shedding, provide lasting protection to wounds, antibacterial properties and promote angiogenesis. In this study, a series of self-healing, adhesive, and antibacterial hydrogels based on gelatin methacrylate (GelMA), acrylated adenine (AA), and CuCl₂ were designed and synthesized via free radical polymerization, hydrogen bond, and ionic bond to promote diabetic wound healing. Overall, GelMA/AA/Cu hydrogels are promising materials to promote diabetic wound healing.

Keywords: Adhesive; Angiogenesis; Antibacterial; Diabetic wound healing; Self-healing.