A suture-free, microenvironment-adaptive hydrogel actively orchestrating inflammation-to-regeneration transition for abdominal wall defect repair.

Abstract

Abdominal wall defect repair remains clinically challenging due to postoperative inflammation, infection, poor tissue regeneration, and the limitations of conventional meshes that provide only passive mechanical support. Here, we developed a suture-free, microenvironment-responsive multifunctional hydrogel (CFPE-EXOS) to actively promote abdominal wall regeneration. The hydrogel is constructed from carboxymethyl chitosan and polyvinyl alcohol via dynamic Schiff base and borate ester crosslinking, enabling suitable tissue adhesion, self-healing, anti-swelling behavior, and long-term mechanical stability. Importantly, CFPE-EXOS achieves spatiotemporally controlled release of epigallocatechin gallate (EGCG) and bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos) in response to acidic and oxidative wound microenvironments. EGCG is rapidly released during the early inflammatory phase to exert antibacterial and antioxidant effects, while sustained exosome release subsequently promotes macrophage M2 polarization, angiogenesis, and tissue remodeling through activation of the PI3K/AKT/HIF-1α/VEGF pathway. In vitro, CFPE-EXOS exhibited excellent biocompatibility, hemostatic ability, antibacterial activity, and reactive oxygen species scavenging capacity. In a rat full-thickness abdominal wall defect model, CFPE-EXOS significantly reduced inflammation, enhanced neovascularization and collagen deposition, and achieved superior repair outcomes compared with polypropylene mesh, without hernia recurrence. This work demonstrates a paradigm shift from passive reinforcement to active, intelligent regeneration for abdominal wall repair, highlighting the translational potential of microenvironment-responsive hydrogels.