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.

中文翻译：

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使用接种在壳聚糖/纳米羟基磷灰石-P24 纳米复合支架中的脂肪源性基质细胞和脐静脉内皮细胞修复骨质疏松性骨缺损

背景。骨质疏松病理条件下骨缺损病变的细胞再生和血供受到限制，这使得骨质疏松骨缺损的愈合仍然是一个巨大的挑战。目前主要抑制骨吸收的治疗策略对骨质疏松性骨缺损并不总是令人满意，这使得开发新疗法成为迫切需要。方法. 此前，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，用于控制骨形态发生蛋白 2 衍生肽 (P24) 的递送。在这项研究中，我们确定了用 CS-P24/nHA 纳米复合支架共培养脂肪来源的基质细胞 (ADSCs) 和人脐静脉内皮细胞 (HUVECs) 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来评估共培养的直接影响。结果。与单独的 ADSCs 或 HUVECs 相比，与 HUVECs 共培养的 ADSCs 显示出显着更大的成骨分化和矿化。与 ADSCs 和 HUVECs 共培养的 CS-P24/nHA 支架在诱导骨质疏松性骨修复方面更有效，如微型计算机断层扫描和卵巢切除大鼠临界大小颅骨缺损的组织学所证明的那样。在 4 周和 8 周后，与用支架加 ADSC 或支架加 HUVEC 处理的缺陷相比，用 CS-P24/nHA 纳米复合支架加 ADSC/HUVEC 共培养处理的颅骨缺损具有更大的修复面积和更好的骨结构重建。结论。总之，ADSCs 和 HUVECs 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。