Development of an Injectable Tissue Adhesive Hybrid Hydrogel for Growth Factor-Free Tissue Integration in Advanced Wound Regeneration

The development of injectable hydrogels with tunable multifunctional properties, for example, adhesive, elastic, swelling, biodegradable, and wound-healing properties that mimic the dynamic-healing process of skin regeneration, is currently a major challenge in tissue regeneration. Here, we report a fillable topical formulation of injectable gelatins (IGs) for the integration of advanced excisional wounds. Bioresorbable temperature-sensitive block copolymer was conjugated to the backbone of gelatins to form a dynamic coordinative network of IGs. The flexible IG precursors transformed to viscoelastic hydrogel at the subcutaneous tissues with cell affinity and tissue adhesive properties. The microporous dynamic network of IGs allows access to nutrients and recruits immune cells that accelerate neovascularization within a hydrogel network. Combined with adhesive and neovascularization properties, the IGs alone exhibit accelerated wound healing in open wounds featured by skin appendages without scar formation. More remarkably, in an excisional wound (1 cm × 1 cm) animal model, the IGs promoted the wound healing as observed by the skin appendages. Furthermore, histological analysis demonstrated that IGs not only accelerate the rate of wound healing but also promoted the quality of wound healing observed by collagen deposition and neovascularization. The in situ forming IGs with a superior adhesive property can be considered as promising wound dressing materials for the treatment of multiple wounds, without the need for the encapsulation of biofactors or antibacterial metals. The IGs prepared in this study can also be employed to repair tissues or organs using minimal invasive administration