Promoting Radial Repair in Rabbits through BMP-9 Overexpression in Adipose-Derived Stem Cells Loaded with ICA/nHAC/PLA

Background Bone defects commonly cause delayed bone healing and local dysfunction. Both adipose-derived stem cells (ADSCs) and icariin (ICA)-loaded nano-hydroxyapatite/collagen/polylactic acid (nHAC/PLA) have been reported to promote osteoblast metabolism and accelerate fracture healing. Aim The aim of this study was to explore the mechanism of ADSCs combined with ICA-loaded nHAC/PLA in regulating bone defects. Methods The effects of ICA and BMP-9 (Bone morphogenetic protein-9) overexpression on cell viability and osteogenic differentiation of ADSCs were measured by qRT-PCR, western blotting and alkaline phosphatase (ALP) assay. Alizarin red staining examined the formation of mineralized nodules in ADSCs. Finally, radial defect of rabbit model was established, and administrated by ADSCs with BMP-9 overexpression combined with ICA-loaded nHAC/PLA. The new bone formation was detected by X-ray, immunohistochemistry and Hematoxylin and eosin staining. Results BMP-9 overexpression significantly increased ALP activity and mineralized nodule formation in ADSCs, effects that were amplified by ICA. This combination also upregulated the expression of osteogenic markers (BMP-9, OCN, OPN, COL-1, BSP, Runx-2) and influenced key signaling pathways (p38 MAPK, JNK, ERK). In vivo, the treatment group showed enhanced radial bone repair. Conclusions Our findings indicate that the combination of BMP-9-overexpressed ADSCs and ICA-loaded nHAC/PLA scaffolds is effective in promoting bone repair, offering a potential therapeutic strategy for bone defects. Core tip BMP-9 overexpression promoted osteogenic differentiation and proliferation of ADSCs. BMP-9 overexpression combined with ICA promoted osteogenesis in ADSCs. ADSCs with BMP-9 overexpression and ICA-loaded nHAC/PLA promoted radial repair.