Repair of Osteoporotic Bone Defects Using Adipose-Derived Stromal Cells and Umbilical Vein Endothelial Cells Seeded in Chitosan/Nanohydroxyapatite-P24 Nanocomposite Scaffolds
Repair of Osteoporotic Bone Defects Using Adipose-Derived Stromal Cells and Umbilical Vein Endothelial Cells Seeded in Chitosan/Nanohydroxyapatite-P24 Nanocomposite Scaffolds
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DOI：
10.1155/2021/6237130
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发表时间：
2021-08
影响因子：
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通讯作者：
Yifei Fang;Yong Gong;Zhijian Yang;Yan Chen
中科院分区：
文献类型：
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作者：
Yifei Fang;Yong Gong;Zhijian Yang;Yan Chen
背景骨质疏松症的病理条件限制了骨缺损病变的细胞再生和血供，使骨质疏松症骨缺损的愈合仍面临巨大挑战。目前以抑制骨吸收为主的治疗策略对骨质疏松性骨缺损的治疗效果并不理想，迫切需要开发新的治疗方法。方法.在此之前，我们制备了壳聚糖/纳米羟基磷灰石（CS/nHA）仿生纳米复合支架，用于骨形态发生蛋白2衍生肽（P24）的可控递送。在这项研究中，我们确定了脂肪来源的基质细胞（ADSCs）和人脐静脉内皮细胞（HUVECs）与CS-P24/nHA纳米复合支架共培养对骨质疏松性骨缺损愈合的影响。采用体外混合共培养模型评估共培养的直接效应。结果与单独的ADSC或HUVECs相比，ADSC与HUVECs共培养显示出显著更高的成骨分化和矿化。CS-P24/nHA支架与ADSCs和HUVECs共培养在诱导骨质疏松性骨修复方面更有效，如卵巢切除大鼠中临界尺寸颅骨缺损的显微计算机断层扫描和组织学所示。与用支架加ADSC或支架加HUVEC治疗的缺损相比，用CS-P24/nHA纳米复合支架加ADSC/HUVEC共培养物治疗的颅骨缺损在4周和8周后具有更大的修复面积和更好的骨结构重建。结论总之，ADSCs和HUVEC与CS-P24/nHA纳米复合支架的共培养是修复骨质疏松性骨缺损的有效组合。
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.