Abstract
We aimed to evaluate the integration of stem cells with injectable microspheres loaded with growth factors using a chitosan (CS) scaffold to promote healthy bone regeneration. We prepared and injected CS scaffolds containing adipose-derived stem cell (ADSC)-, vascular endothelial growth factor (VEGF)-, and bone morphogenetic protein-2 (BMP-2)-loaded nanohydroxyapatite (nHA)/poly lactic-co-glycolic acid microspheres (PLGAs) into critical-sized mandibular bone defects in rabbits. This injectable hydrogel displayed excellent physicochemical properties and degradability and achieved sustainable release and bioactivity preservation for both BMP-2 and VEGF. Computed tomography imaging and gross and histological observations indicated that bone defect cavities in the control group did not narrow and were filled with granulation tissue. Limited new bone formation for the first 12 weeks post-operation was observed in the defect cavities of the VEGF group; the scaffold degraded gradually and was replaced with fibrous connective tissue. In the BMP-2 or BMP-2/VEGF groups, bone defect cavities narrowed with time and healed completely after 12 weeks; scaffolds gradually degraded and infiltrated tightly into the surrounding tissues. Overall, the BMP-2/VEGF group demonstrated greater new bone formation, faster healing, and better callus remodeling. Simultaneous application of VEGF and BMP-2, therefore, promoted ossification and vascularization in critical-sized rabbit mandibular bone defects.
Published Version
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