Visible Light Induced DLP-Printed Oxygen-Releasing TPMS Scaffolds Mitigate Early Hypoxia in Bone Defects

Oxygen deprivation within large or poorly vascularized bone defects remains a key barrier to successful regeneration, especially during the early postimplantation period before vascular ingrowth. Here, the development of COSnPPOD (CaO₂-Silica NP Platform for Osteogenic Development) is reported, a visible light digital light processing-printed hydrogel scaffold that integrates oxygen-releasing nanoparticles (NPs) within a Primitive-type triply periodic minimal surface architecture. The scaffold combines a gelatin methacrylate-poly(ethylene glycol) diacrylate matrix with calcium peroxide (CaO₂)-loaded hollow silica NPs, enabling localized, short-term oxygen release while preserving structural fidelity. COSnPPOD scaffolds demonstrate favorable degradation kinetics, tunable stiffness, and increased protein adsorption in vitro. In a preosteoblast model, COSnPPOD maintains cell viability and supports osteogenic gene expression without cytotoxic effects. While overall gene expression is comparable to controls, a 16-fold increased expression of phosphoprotein 1 (Spp1) suggests scaffold-driven activation of matrix remodeling pathways. In vivo, COSnPPOD scaffolds enhance bone regeneration in a murine calvarial defect model, with significantly greater bone formation and collagen deposition than untreated defects and hydrogel controls. Additionally, vascular endothelial growth factor immunostaining is increased within the defect, consistent with a proangiogenic response, and no systemic toxicity is observed. These findings establish COSnPPOD as a promising scaffold system that combines sustained oxygenation with biomimetic geometry to support localized bone regeneration.