Enhancement of type H vessels in bone repair of rat tibial defects treated with stromal vascular fraction-collagen sponge composites

BACKGROUND: To address the clinical limitations of autografts and allografts in bone defect repair, this study aimed to develop a novel composite graft by combining adipose-derived stromal vascular fraction (SVF) with medical-grade collagen sponge, aiming to achieve structural support and functional vascularization simultaneously.
Methods: A rat tibial defect model was established, and the SVF was combined with medical collagen sponge to form a composite for implantation. In vitro experiments were conducted to detect the proliferation activity, osteogenic differentiation ability, and pro-angiogenic potential of SVF cells. In vivo experiments were used to evaluate the bone volume fraction (BV/TV) and bone mineral density (BMD) in the bone defect area and observe the formation of CD31hi/Emcnhi vessels (H-type vessels). Immunofluorescence staining was performed to analyze the expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).
Results: In vitro SVF exhibited robust proliferation, osteogenic differentiation, and secreted factors that significantly enhanced endothelial cell migration and tube formation. In vivo, the SVF-collagen sponge composite significantly increased the bone volume fraction (BV/TV) and bone mineral density(BMD) at 9 weeks post-operation compared to controls. Importantly, at this 9-week time point, the SVF composite group demonstrated a greater abundance of type H vessels within the defect compared to both the scaffold-only and blank control groups. This was accompanied by sustained upregulation of VEGF and PDGF expression. 
Conclusion: The SVF-collagen sponge composite promotes bone regeneration in a rat defect model. The mechanism is associated with fostering a pro-angiogenic microenvironment, characterized by increased type H vessel formation and elevated expression of VEGF and PDGF, suggesting enhanced angiogenesis-osteogenesis coupling. This autologously-sourced composite shows promising translational potential due to its straightforward preparation and biocompatibility.