Abstract
Background. The cell regeneration and blood supply of bone defect lesions are restricted under osteoporotic pathological conditions, which make the healing of bone defect of osteoporosis still a great challenge. The current therapeutic strategies that mainly inhibit bone resorption are not always satisfactory for osteoporotic bone defects, which make the development of new therapies an urgent need. Methods. Previously, we prepared chitosan/nanohydroxyapatite (CS/nHA) biomimetic nanocomposite scaffolds for controlled delivery of bone morphogenetic protein 2-derived peptide (P24). In this study, we determined the effect of coculturing adipose-derived stromal cells (ADSCs) and human umbilical vein endothelial cells (HUVECs) with the CS-P24/nHA nanocomposite scaffolds on osteoporotic bone defect healing. In vitro mixed coculture models were employed to assess the direct effects of coculture. Results. ADSCs cocultured with HUVECs showed significantly greater osteogenic differentiation and mineralization compared with ADSCs or HUVECs alone. The CS-P24/nHA scaffold cocultured with ADSCs and HUVECs was more effective in inducing osteoporotic bone repair, as demonstrated by micro-computed tomography and histology of critical-sized calvariae defects in ovariectomized rats. Calvariae defects treated with the CS-P24/nHA nanocomposite scaffold plus ADSC/HUVEC coculture had a greater area of repair and better reconstitution of osseous structures compared with defects treated with the scaffold plus ADSCs or the scaffold plus HUVECs after 4 and 8 weeks. Conclusion. Taken together, coculture of ADSCs and HUVECs with the CS-P24/nHA nanocomposite scaffold is an effective combination to repair osteoporotic bone defects.
Highlights
Osteoporosis is a metabolic systemic bone disease characterized by decreased bone mass, increased bone fragility, and weakened bone strength [1]
The Cell Counting Kit-8 (CCK-8) analysis showed that cell number significantly increased in each of the adipose-derived stromal cells (ADSCs), human umbilical vein endothelial cells (HUVECs), and ADSC/HUVEC coculture groups
This study demonstrated that coculture of HUVECs and ADSCs in CS-Peptide 24 (P24)/nHA nanocomposite scaffolds can promote cell proliferation and osteogenic differentiation
Summary
Osteoporosis is a metabolic systemic bone disease characterized by decreased bone mass, increased bone fragility, and weakened bone strength [1]. Existing bone defect implants, such as autogenous bone and artificial bone, are considered to lack sufficient biological activity to induce differentiation of endogenous MSCs into osteoblasts in patients with osteoporosis. They have an insufficient effect on osteoporotic bone regeneration [9]. We determined the effect of coculturing adipose-derived stromal cells (ADSCs) and human umbilical vein endothelial cells (HUVECs) with the CS-P24/nHA nanocomposite scaffolds on osteoporotic bone defect healing. The CS-P24/nHA scaffold cocultured with ADSCs and HUVECs was more effective in inducing osteoporotic bone repair, as demonstrated by micro-computed tomography and histology of critical-sized calvariae defects in ovariectomized rats. Coculture of ADSCs and HUVECs with the CS-P24/nHA nanocomposite scaffold is an effective combination to repair osteoporotic bone defects
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