Advancing homogeneous networking principles for the development of fatigue-resistant, low-swelling and sprayable hydrogels for sealing wet, dynamic and concealed wounds in vivo.

Effective sealing of wet, dynamic and concealed wounds remains a formidable challenge in clinical practice. Sprayable hydrogel sealants are promising due to their ability to cover a wide area rapidly, but they face limitations in dynamic and moist environments. To address this issue, we have employed the principle of a homogeneous network to design a sprayable hydrogel sealant with enhanced fatigue resistance and reduced swelling. This network is formed by combining the spherical structure of lysozyme (LZM) with the orthotetrahedral structure of 4-arm-polyethylene glycol (4-arm-PEG). We have achieved exceptional sprayability by controlling the pH of the precursor solution. The homogeneous network, constructed through uniform cross-linking of amino groups in protein and 4-arm-PEG-NHS, provides the hydrogel with outstanding fatigue resistance, low swelling and sustained adhesion. In vitro testing demonstrated that it could endure 2000 cycles of underwater shearing, while in vivo experiments showed adhesion maintenance exceeding 24 h. Furthermore, the hydrogel excelled in sealing leaks and promoting ulcer healing in models including porcine cardiac hemorrhage, lung air leakage and rat oral ulcers, surpassing commonly used clinical materials. Therefore, our research presents an advanced biomaterial strategy with the potential to advance the clinical management of wet, dynamic and concealed wounds.