A regenerative tissue adhesive based on PEG-NHS crosslinked porcine urinary bladder matrix hydrogel for rapid sealing and enhanced defect repair.

Tissue adhesives have attracted significant interest owing to their convenience and excellent sealing properties. However, commercial adhesives are often limited by cytotoxicity, excessive swelling, and a lack of pro-regenerative bioactivity. Porcine urinary bladder matrix (UBM), an excellent extracellular matrix (ECM) material, has demonstrated substantial potential in tissue repair and regeneration. Here, we developed an injectable ECM hydrogel adhesive by crosslinking between poly(ethylene glycol)-N-hydroxysuccinimide (PEG-NHS) and enzymatically digested UBM (DUBM), enabling in situ gelation for immediate sealing. Concurrently, the NHS groups reacted with amino groups on the tissue surface, endowing the adhesive with robust interfacial bonding for both tissue adhesion and implant fixation. The DUBM adhesive exhibited high adhesive strength, low swelling, favorable burst pressure, and significantly improved cellular affinity compared to conventional PEG hydrogels. In vivo, it effectively sealed vascular defects and rapidly secured implants. In abdominal wall defect models, the DUBM adhesive provided high mechanical strength and low swelling, enabling stable structural support while promoting collagen deposition, cell proliferation, and neovascularization, thereby accelerating tissue healing. These findings highlight the promising clinical translation potential of the DUBM hydrogel as a regenerative tissue adhesive.