Bilateral defects (diameter 8 mm) in the medial tibial head of senile, osteopenic female sheep (n = 48; 9.63 ± 0.10 years; mean ± SEM) were treated with hydroxyapatite (HA)/beta-tricalcium phosphate (β-TCP)/dicalcium phosphate dihydrate (DCPD; brushite) cylinders coated with BMP-2 (25 or 250 micrograms) or growth differentiation factor (GDF)-5 (125 or 1250 micrograms; left side); cylinders without BMP served as controls (right side). Three, 6, and 9 months post-operation (n = 6 each group), bone structure and formation were analyzed in vivo by X-ray and ex vivo by osteodensitometry, histomorphometry, and micro-computed tomography (micro-CT) at 3 and 9 months. Semi-quantitative X-ray evaluation showed significantly increasing bone densities around all implant cylinders over time. High-dose BMP-2-coated cylinders (3 and 9 months) and low-dose GDF-5-coated cylinders (3 and 6 months) demonstrated significantly higher densities than controls (dose-dependent for BMP-2 at 3 months). This was confirmed by osteodensitometry at 9 months for high-dose BMP-2-coated cylinders (and selected GDF-5 groups), and was again dose-dependent for BMP-2. Osteoinduction by BMP-2 was most pronounced in the adjacent bone marrow (dynamic histomorphometry/micro-CT). BMP-2 (and partially GDF-5) significantly increased the bone formation in the vicinity of HA/TCP/DCPD cylinders used to fill tibial bone defects in senile osteopenic sheep and may be suitable for surgical therapy of critical size, non-load-bearing bone defects in cases of failed tibial head fracture or defect healing.

Graphical Abstract

中文翻译：

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BMP-2（和部分 GDF-5）涂层显着加速和增强羟基磷灰石/磷酸三钙/透钙磷石植入柱附近的骨形成，用于治疗老年骨质疏松羊的胫骨骨缺损

 采用羟基磷灰石 (HA)/β-磷酸三钙 (β-TCP)/ 治疗老年骨质疏松母羊 ( n = 48; 9.63 ± 0.10 岁; 平均值 ± SEM) 胫骨内侧缺损 (直径 8 mm )涂有 BMP-2（25 或 250 微克）或生长分化因子 (GDF)-5（125 或 1250 微克；左侧）的二水磷酸二钙（DCPD；透钙磷石）圆柱体；没有 BMP 的气缸作为对照（右侧）。术后 3、6 和 9 个月（ 每组n = 6），通过 X 射线对体内骨结构和形成进行分析，并通过骨密度测量、组织形态测量和微型计算机断层扫描 (micro-CT) 进行体外骨结构和形成分析。和9个月。半定量 X 射线评估显示，随着时间的推移，所有种植体圆柱体周围的骨密度均显着增加。高剂量 BMP-2 涂层圆柱体（3 个月和 9 个月）和低剂量 GDF-5 涂层圆柱体（3 个月和 6 个月）表现出明显高于对照组的密度（3 个月时 BMP-2 的剂量依赖性）。对于高剂量 BMP-2 涂层圆柱体（和选定的 GDF-5 组），这一点在 9 个月时通过骨密度测定法得到证实，并且对于 BMP-2 再次呈剂量依赖性。BMP-2 的骨诱导在邻近骨髓中最为明显（动态组织形态计量学/显微 CT）。BMP-2（和部分 GDF-5）显着增加了用于填充老年骨质疏松羊胫骨骨缺损的 HA/TCP/DCPD 圆柱体附近的骨形成，并且可能适合于临界尺寸、非负荷的手术治疗。在胫骨骨头骨折或缺损愈合失败的情况下承受骨缺损。

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