Engineering M2 macrophage-derived exosome-loaded PEG hydrogels for preventing pancreatic leakage and facilitating anastomotic healing

Pancreaticojejunostomy presents significant challenges due to the high risk of complications such as pancreatic leakage and poor tissue regeneration. However, current approaches to enhance surgical outcomes are often limited by issues related to biocompatibility, tissue repair efficacy, and inflammation modulation. Here, we report the potential of an adhesive polyethylene glycol (PEG) hydrogel incorporating M2 macrophage-derived exosomes (PEG/Exo M2 ) for improving tissue repair in pancreaticojejunostomy. M2 macrophage-derived exosomes exhibit potent anti-inflammatory properties and pro-angiogenic effects, making them ideal candidates for tissue regeneration. The PEG/Exo M2 hydrogel demonstrates excellent mechanical strength and strong antibacterial activity. In vitro assays reveal that the PEG/Exo M2 hydrogel promotes angiogenesis and cell migration while modulating inflammatory responses. In animal models, the PEG/Exo M2 hydrogel effectively reduces fibrosis and inflammation in a subcutaneous implantation model, and significantly improves tissue regeneration. In a pancreaticojejunostomy model, the PEG/Exo M2 hydrogel facilitates wound sealing, lowers the risk of pancreatic leakage, and enhances anastomotic repair, outperforming conventional sutures. These results highlight the PEG/Exo M2 hydrogel as a promising biomaterial for tissue repair and regeneration, with strong potential for clinical applications in surgical wound healing.