3D-printed PRP-infused double-network hydrogels orchestrate inflammation resolution and vascular regeneration in infected wounds

Bacterial infection and excessive inflammation critically impede wound healing, necessitating the development of multifunctional bioactive materials. Herein, we report a biodegradable composite hydrogel (PPG) fabricated via projection-based 3D biophotocuring, comprising an interpenetrating double-network of gelatin methacryloyl (GelMA) and poly-L-lysine methacryloyl (PLMA), embedded with platelet-rich plasma (PRP). The resulting hydrogel exhibits potent antibacterial activity and robust inhibition of biofilm formation, alongside integrated anti-inflammatory and pro-angiogenic functions. <i>In vitro,</i> incorporating PRP promotes the migratory and proliferative activity of human skin fibroblasts and facilitated macrophage polarization toward the M2 phenotype. <i>In vivo</i>, PPG accelerates wound closure in bacteria-infected models by facilitating re-epithelialization, collagen remodeling, and neovascularization, as evidenced by sustained α-SMA and elevated CD31 expression. Mechanistically, PPG activates the PI3K/AKT/eNOS signaling axis, further supporting angiogenesis and extracellular matrix deposition. RNA-seq validation showed that PPG upregulated DEFB4 and SPRR2F, promoting wound healing and modulating inflammation. Collectively, this work presents a 3D-printed, bioactive hydrogel platform with synchronized antibacterial, immunomodulatory, and pro-regenerative properties, offering strong translational potential for treating infected wounds.