<p>A novel biocompatible mesh composed of a polyacrylamide–alginate hydrogel matrix loaded with puerarin and functionalized with a chitosan-based adhesive layer is designed for abdominal wall reconstruction. This multifunctional mesh exhibits robust tissue adhesion, eliminating the need for mechanical fixation during surgery, thereby simplifying operative procedures. Moreover, the mesh demonstrates adequate mechanical strength to withstand maximal abdominal pressure and exhibits significant antibacterial activity, which helps prevent postoperative infections. In a rat model of full-thickness abdominal wall defect, the puerarin-loaded mesh markedly enhanced tissue repair by promoting early neovascularization, inducing M2 macrophage polarization, attenuating inflammatory responses and facilitating collagen deposition. Mechanistic studies revealed that these beneficial effects are mediated through activation of the PI3K/AKT/HIF-1α/VEGF signaling pathway. Our findings suggest that this innovative multifunctional hydrogel mesh holds great promise for efficient and complication-free repair of abdominal wall defects.</p>