Mitra, Indranath

Abstract 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 (CaO 2 –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 (CaO 2 )‐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.

Abstract Segmental bone defects, often clinically treated with nondegradable poly(methylmethacrylate) (PMMA) in multistage surgeries, present a significant clinical challenge. Our study investigated the efficacy of 3D printed biodegradable polycaprolactone fumarate (PCLF)/PCL spacers in a one‐stage surgical intervention for these defects, focusing on early bone regeneration influenced by spacer porosities. We compared nonporous PCLF/PCL and PMMA spacers, conventionally molded into cylinders, with porous PCLF/PCL spacers, 3D printed to structurally mimic segmental defects in rat femurs for a 4‐week implantation study. Histological analysis, including tissue staining and immunohistochemistry with bone‐specific antibodies, was conducted for histomorphometry evaluation. The PCLF/PCL spacers demonstrated compressive properties within 6 ± 0.5 MPa (strength) and 140 ± 15 MPa (modulus). Both porous PCLF/PCL and Nonporous PMMA formed collagen‐rich membranes (PCLF/PCL: 92% ± 1.3%, PMMA: 86% ± 1.5%) similar to those induced in the Masquelet technique, indicating PCLF/PCL's potential for one‐stage healing. Immunohistochemistry confirmed biomarkers for tissue regeneration, underscoring PCLF/PCL's regenerative capabilities. This research highlights PCLF/PCL scaffolds' ability to induce membrane formation in critical‐sized segmental bone defects, supporting their use in one‐stage surgery. Both solid and porous PCLF/PCL spacers showed adequate compressive properties, with the porous variants exhibiting BMP‐2 expression and woven bone formation, akin to clinical standard PMMA. Notably, the early ossification of the membrane into the pores of porous scaffolds suggests potential for bone interlocking and regeneration, potentially eliminating the need for a second surgery required for PMMA spacers. The biocompatibility and biodegradability of PCLF/PCL make them promising alternatives for treating critical bone defects, especially in vulnerable patient groups.