Injectable Dual-Crosslinked Poly(oligo(Ethylene Glycol) Methacrylate) Hydrogels Inspired by Mussel Adhesion for Cutaneous Wound Healing and Functional Tissue Regeneration.

Abstract

Traditional dermal wound closure methods, such as sutures and staples, are invasive, causing soft tissue trauma, increasing the likelihood of inflammation and infections. Alternatively, while existing tissue adhesives can seal and adhere to wounds, they may cause immunogenic responses, tissue necrosis, restricted movement, and wound disruption upon removal, leading to secondary injuries and scarring. Herein, injectable poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA)-dopamine (DA) hydrogels co-crosslinked via hydrazone linkages and dopamine self-polymerization are fabricated that promote high water retention, effective tissue adhesion, re-epithelialization, and functional skin regeneration. The dual crosslinking mechanism allows for gelation as fast as 24 s (enabling injection and rapid filling of irregularly-shaped wounds) while achieving compressive moduli of up to 37 kPa and skin adhesion strengths of up to 3.3 kPa. In a 14-day stented mouse skin wound model, the POEGMA-DA hydrogels induce no significant inflammation, effective tissue adhesion, and promote tissue regeneration, including enhanced collagen remodelling, 3-5× higher hair follicle, ≈5-7× higher sebaceous gland and 1.5-1.7× higher blood vessel regeneration at the excision site compared to untreated wounds. These hydrogels represent an alternative nontoxic wound closure system that mimics the soft skin tissue environment to promote regeneration after acute superficial dermal wounds.