Rapid gelation of oxidized hyaluronic acid and succinyl chitosan for integration with insulin-loaded micelles and epidermal growth factor on diabetic wound healing

Designing wound dressing materials with outstanding therapeutic effects, self-healing, adhesiveness and suitable mechanical property has great practical significance in healthcare, especially for joints skin wound healing. Here, we designed a kind of self-healing injectable micelle/hydrogel composites with multi-functions as wound dressing for joint skin damage. By combining the dynamic Schiff base and copolymer micelle cross-linking in one system, a series of hydrogels were prepared by mixing quaternized chitosan (QCS) and benzaldehyde-terminated Pluronic®F127 (PF127-CHO) under physiological conditions. The inherent antibacterial property, pH-dependent biodegradation and release behavior were investigated to confirm multi-functions of wound dressing. The hydrogel dressings showed suitable stretchable and compressive property, comparable modulus with human skin, good adhesiveness and fast self-healing ability to bear deformation. The hydrogels exhibited efficient hemostatic performance and biocompatibility. Moreover, the curcumin loaded hydrogel showed good antioxidant ability and pH responsive release profiles. In vivo experiments indicated that curcumin loaded hydrogels significantly accelerated wound healing rate with higher granulation tissue thickness and collagen disposition and upregulated vascular endothelial growth factor (VEGF) in a full-thickness skin defect model. Taken together, the antibacterial adhesive hydrogels with self-healing and good mechanical property offer significant promise as dressing materials for joints skin wound healing.

Optimum healing of a cutaneous wound requires a well-orchestrated integration of the complex biological and molecular events of cell migration and proliferation, and of extracellular matrix deposition and remodelling. Cellular responses to inflammatory mediators, growth factors, and cytokines, and to mechanical forces, must be appropriate and precise. However, this orderly progression of the healing process is impaired in chronic wounds, including those due to diabetes. Several pathogenic abnormalities, ranging from disease-specific intrinsic flaws in blood supply, angiogenesis, and matrix turnover to extrinsic factors due to infection and continued trauma, contribute to failure to heal. Yet, despite these obstacles, there is increasing cause for optimism in the treatment of diabetic and other chronic wounds. Enhanced understanding and correction of pathogenic factors, combined with stricter adherence to standards of care and with technological breakthroughs in biological agents, is giving new hope to the problem of impaired healing.