Epidermal Growth Factor-Derived Thermoresponsive Nanocomposite Hydrogel for Accelerating Tissue Regeneration and Cutaneous Wound Healing

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Skin wound healing involves a complex process hindered by limited cellular regeneration capacity, persistent inflammation, and insufficient angiogenesis. Epidermal growth factor (EGF) is a natural signaling molecule that promotes proliferation and migration at multiple stages of wound healing and tissue repair. However, rapid proteolytic degradation and instability within the harsh wound microenvironment constrain its bioavailability and therapeutic efficacy. In this study, an innovative recombinant EGF-loaded thermoresponsive nanocomposite hydrogel (EGF-LPs@PF127) was developed for multimodal wound healing management to enhance the effectiveness of growth factor therapy. This multifunctional hydrogel integrates EGF-loaded liposome as a nanocomposite to shield it from enzymatic breakdown and triblock copolymer Pluronic F-127 (PF127) as the thermoresponsive component for self-adapting dressings. With efficient encapsulation and sustained release of EGF, the multifunctional hydrogel demonstrates a remarkable ability to promote the proliferation and migration of keratinocytes and reduce the proinflammatory factor levels in macrophages. Furthermore, EGF-LPs@PF127 hydrogel administered locally undergoes in situ gelation at body temperature to adapt to wound shapes in a mouse full-thickness skin wound model. The EGF-functionalized nanocomposite hydrogel administration restores the epidermal integrity, reduces proinflammatory factors, and facilitates collagen deposition and angiogenesis, ultimately accelerating wound repair. This work underscores the efficacy of the nanoarchitecture-integrated hydrogel as a superior platform for growth factor delivery, holding considerable promise for enhancing tissue regeneration and wound healing management.