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

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. In vitro, incorporating PRP promotes the migratory and proliferative activity of human skin fibroblasts and facilitated macrophage polarization toward the M2 phenotype. In vivo, 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.