3D-printed biomimetic bone scaffold loaded with lyophilized concentrated growth factors promotes bone defect repair by regulation the VEGFR2/PI3K/AKT signaling pathway

Abstract

This study investigates the effects of concentrated growth factors (CGF) and bone substitutes on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs), as well as the development of a novel 3D-printed biomimetic bone scaffold. Based on the structure of cancellous bone, 3D-printed bionic bone with sustainable release of growth factors and Ca²⁺ was prepared. Using BMSCs and EA.hy926 in co-culture with the bionic bone scaffold, experimental results demonstrate that this bionic structural design enhances cell proliferation and adhesion, and that the bionic bone possesses the ability to promote bone and vascular regeneration directly. Transcriptomics, western blot analysis, and flow cytometry are employed to investigate the effects of CGF and Ca²⁺ on the signaling pathways of BMSCs. The study reports that vascular endothelial growth factor (VEGF) released by CGF activated VEGFR2 on BMSCs, leading to Ca²⁺ influx and activation of the PI3K/AKT signaling pathway, thereby influencing osteogenesis. Animal experiments confirm the ability of the bionic bone to promote osteogenesis in vivo, and its unique degradation pattern accelerates the in vivo repair of bone defects. In conclusion, this study presents a novel biomimetic strategy and, for the first time, explores the potential mechanism by which VEGF and Ca²⁺ regulate BMSCs differentiation through the VEGFR2/PI3K/AKT signaling pathway. These insights offer a new perspective for the development of innovative bone substitute materials.

Keywords: Bone regeneration; Bone tissue engineering; Concentrated growth factors; Osteogenic differentiation; Vascularization.