S53P4 Bioactive Glass Inorganic Ions for Vascularized Bone Tissue Engineering by Dental Pulp Pluripotent-Like Stem Cell Co-cultures

Vascularization of large bone grafts is one of the main challenges that limit the clinical application of bone tissue engineering (BTE). In this way, cell cocultures, which involve the cross-talk between endothelial and osteogenic cells, have shown to be an effective strategy for in vitro prevascularization. Dental pulp represents an easily accessible autologous source of adult stem cells. A subset of these cells, named dental pulp pluripotent-like stem cells (DPPSCs), shows high plasticity and great capacity to differentiate into different tissues. Here, we suggested a combination of bone-like DPPSC and endothelial-like DPPSC to induce vascularized bone formation from a unique stem cell population. In addition, we evaluated the use of inorganic ions dissolved from S53P4 bioactive glass (BaG) in different medium compositions. Results show that endothelial medium with BaG extracts provides an effective way to enhance both endothelial and osteogenic processes, supporting the formation of vascular-like structures and mineralization simultaneously. Furthermore, 3D DPPSC cocultures in the same medium conditions demonstrated the formation of vessel-like structures that appear to be functional as indicated by the presence of an internal lumen. Overall, these results would provide a new promising system for the prevascularization of BTE constructs.