Pre-vascularized bioactive scaffold driven by bidirectional cellular communication enhances bone repair

Bone, characterized by its extensive vascularization, relies on angiogenesis as a fundamental prerequisite for successful regeneration. However, conventional bone implant materials often exhibit limitations such as insufficient vascularization, leading to cellular necrosis and delayed host tissue infiltration. To address these challenges, this study integrates 3D printing and photo-crosslinking technologies to develop a pre-vascularized bioactive scaffold driven by endothelial cells (ECs)/ bone marrow mesenchymal stem cells (BMSCs) bidirectional cellular communication, aiming to facilitate the rapid reconstruction of vascular and bone networks. The results demonstrate that the scaffold not only enhances the vascularization of ECs, but also activates BMP-2 and TGF-β signaling of BMSCs through EC-secreted growth factors, thus synergistically enhancing the osteogenic differentiation of BMSCs. In a rat femoral defect model, this bioactive pre-vascularized scaffold exhibited robust matrix deposition and osteoinductive capacity, offering a promising strategy to enhance bone regeneration and address bone defects.