Gmsc-Apoevs Enhance Implant Osteointegration In Ovariectomy-Induced Osteoporotic Rats

To investigate the therapeutic potential of apoptotic vesicles derived from gingival mesenchymal stem cells (GMSC-apoEVs) in enhancing implant osseointegration under estrogen-deficient conditions and elucidate the underlying mechanisms, thereby proposing a novel cell-free strategy for managing osteoporosis-related implant. Female SD rats (8-week-old) underwent ovariectomy (OVX) to model postmenopausal osteoporosis. Animals were allocated into sham, OVX and apoEV-treated groups. GMSC-apoEVs were administered intravenously per week post OVX, concurrent with titanium implants implanted in femurs at week 4. Bone morphology and osteointegration were assessed via micro-CT, histology assessment (H&E, Masson staining), and biomechanical testing at week 8. In vitro, the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) after GMSC-apoEVs treatment was evaluated using Alizarin Red S, ALP staining and Western blot. Proteomic analysis was used to further explore the molecular mechanisms. GMSC-apoEVs significantly enhanced bone-implant integration in OVX rats, evidenced by increased bone volume, trabecular thickness and biomechanical stability. GMSC-apoEVs restored osteogenic differentiation while decreasing adipogenic differentiation in OVX-BMMSCs. Proteomic analysis revealed GMSC-apoEVs rescued lysosomal dysfunction in OVX-BMMSCs, reactivating osteogenic pathways. GMSC-apoEVs transplantation enhances bone-implant integration in ovariectomized rats by rescuing osteogenic differentiation of BMMSCs via lysosome related pathway, offering a promising cell-free therapeutic approach for implant in estrogen-deficient conditions.