EphrinB2-engineered cPDLSCs/EPCs 3D cell sheets accelerate peri-implant osseointegration via coupled angiogenesis-osteogenesis regulation in canine model

Patients with osteoporosis often lack optimal bone conditions necessary for successful dental implant osseointegration. Consequently, research has focused on improving peri-implant bone regeneration in compromised bone environments. Our previous findings demonstrated that ephrinB2-gene-modified dental stem cells enhanced osteogenic potential and promoted angiogenesis in umbilical vein endothelial cells within a co-culture system. Furthermore, the extracellular matrix (ECM) from these endothelial cells promoted the differentiation of odontogenic stem cells into endothelial cells. Based on these results, we proposed amplifying the biological effects of ephrinB2 to enhance synergistic cell-to-cell and cell-to-matrix interactions within the bone microenvironment. For this purpose, three-dimensional (3D) cell sheets were developed using ephrinB2-overexpressing canine periodontal ligament stem cells (cPDLSCs) co-cultured with endothelial progenitor cells (EPCs). The resulting ephrinB2-cPDLSCs/EPCs 3D cell sheet constructs were placed around dental implants before transplantation into osteoporotic canine mandibles. The impact of this intervention was rigorously evaluated by assessing bone formation and vascular regeneration around the implants. This study provides a solid experimental and theoretical foundation for enhancing dental implant therapies in osteoporotic patients.