Bioceramic modular tissue-engineered bone with rapid vascularization for large bone defects

Abstract

Tackling large bone defects remains a significant clinical challenge due to the limitations in current treatment strategies. This study presents a modular tissue-engineered bone, achieving rapid vascularization within 14 days and showing significant initial stability after implantation. This innovation is driven by the synergy of high-resolution mono-LCD mask photopolymerization 3D printing, electrospinning technology, and photosensitive gel cell carriers, resulting in a bioceramic-electrospun fiber composite scaffold (BECS) that enhances nutrient permeation and mechanical support. Emphasizing biomimicry, the scaffold incorporates an electrospun ultrafine fiber membrane that simulates the periosteum's microvascular structure, crucial for rapid endothelialization of graft lumens. This membrane acts as an advanced carrier for vascular endothelial growth factor (VEGF), facilitating targeted release that significantly promotes vascular regeneration. Our in vitro and in vivo analyses indicate that immediate vascularization and subsequent osteogenesis significantly enhance blood supply and bone regeneration in defect sites. Notably, the application of Human umbilical cord mesenchymal stem cells (UC-MSCs) within the gelatin methacrylate (GelMA) cell carrier ensures uniform distribution and proliferation, essential for balanced bone regeneration. Demonstrating a 75% increase in vascular network formation and a 60% enhancement in osteocalcin (OCN) expression within the initial four weeks, the scaffold supports both rapid vascularization and osteogenesis. This dual-functional tissue-engineered bone represents a significant advancement for treating large bone defects, with the potential to improve current therapeutic strategies substantially.