Postoperative pancreatic fistula remains a challenging complication after pancreaticoduodenectomy. Addressing this issue requires effective strategies to promote anastomotic healing. In this study, we developed a novel hydrogel designed to close pancreaticoenteric anastomosis after pancreaticoduodenectomy. The hydrogel—composed of polyvinyl alcohol, chitosan, and dopamine-modified oxidized hyaluronic acid—exhibited excellent antibacterial, anti-inflammatory, and wound healing properties. It was designed to conform well to the anastomotic site for clinical application. The hydrogel demonstrated good biocompatibility, appropriate mechanical strength, low swelling, and strong adhesive properties, meeting specific requirements for pancreaticoenteric anastomosis environments. Moreover, by activating the cell cycle, it promoted cell proliferation and migration, thereby accelerating anastomotic closure. Addition of the potent broad-spectrum antibiotic meropenem further enhanced its antibacterial efficacy, targeting common microbial species involved in delayed healing and fistula formation after pancreatic surgery. In a rat model of pancreatic fistula, the hydrogel effectively sealed the anastomosis, filled potential suture gaps, and exerted antibacterial, anti-inflammatory, and tissue regeneration–promoting effects around the anastomotic site. Therefore, this hydrogel, with its ideal degradation properties, shows promising application prospects in closing pancreaticoenteric anastomosis following pancreaticoduodenectomy, thereby offering an effective solution to reduce complications such as pancreatic fistula after pancreatic surgery.
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.
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