In situ fused granular hydrogels with ultrastretchability, strong adhesion, and mutli-bioactivities for efficient chronic wound care

Microgels that can be assembled into granular hydrogels have been served as building blocks to promote healing of irregularly shaped wounds. However, current granular hydrogels are non-adhesive and un-stretchable with low Young’s moduli and toughness, which greatly limits their ability to instantly seal the wounds and subsequently provide physical support for further tissue regeneration. Here, we put forward a novel in situ fusion strategy for granular hydrogels, which combined hydration-induced physical interactions and covalent bonds triggered by coupling reagents to achieve ultrastretchability and strong adhesion among fused granular hydrogels (FGHs). Specifically, we developed Zn2+ functionalized nanocomposite microgels (Zn NanoM) that could be in situ assembled into ultrastretchable and strongly adhesive FGHs to in situ fill irregularly shaped wounds, instantly and firmly adhere to tissue wounds. With its remarkable biocompatibility, antibacterial activity, and potent regulation of inflammatory responses through sustained release of Zn2+ ions, the developed FGH could also significantly accelerate wound healing processes in the diabetic rat full-thickness wound models, infected rat full-thickness wound models, and preclinical porcine full-thickness wound models. This work presents a new methodology for in situ fabricating modularized functional hydrogels with high performances, which provides great convenience for various biomedical applications like clinical chronic wound care.