Single Application of Low-Dose, Hydroxyapatite-Bound BMP-2 or GDF-5 Induces Long-Term Bone Formation and Biomechanical Stabilization of a Bone Defect in a Senile Sheep Lumbar Osteopenia Model.
Single Application of Low-Dose, Hydroxyapatite-Bound BMP-2 or GDF-5 Induces Long-Term Bone Formation and Biomechanical Stabilization of a Bone Defect in a Senile Sheep Lumbar Osteopenia Model.
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DOI：
10.3390/biomedicines10020513
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发表时间：
2022-02-21
期刊：
影响因子：
4.7
通讯作者：
Kinne RW
中科院分区：
文献类型：
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作者：
Hasenbein I;Sachse A;Hortschansky P;Schmuck KD;Horbert V;Anders C;Lehmann T;Huber R;Maslaris A;Layher F;Braun C;Roth A;Plöger F;Kinne RW
比较羟基磷灰石（HA）颗粒对骨形态发生BMP-2和GDF-5的影响；用酶联免疫吸附法测定其在磷酸盐缓冲盐水（PBS）或绵羊血清中的体外释放度。老龄、骨质减少的母羊（n = 72; 9.00±0.11岁；平均值±SEM）产生腰椎(L)椎体骨缺损（Ø 3.5 mm）。处理方法：(a) HA颗粒（2.5 mg; L5）；或(b)包被BMP-2（1µg; 10µg）或GDF-5（5µg; 50µg; L4；所有组n = 6）的颗粒。未接触椎体（L3）作为对照。治疗后3个月和9个月，通过骨密度测定法、组织形态测定法和生物力学测试评估骨形成。血清中14天BMP的累积释放量较高（76-100%）。1.4% PBS。任何一种生长因子的HA颗粒在体内诱导骨形成的结果表明：(i)骨体积、骨小梁和皮质厚度显著增加（总体上HA + BMP比接近注射通道的对照组分别增加71%、110%和37%）；（ii）对骨矿物质密度、骨形成和抗压强度的部分显著影响（增加17%；9个月；GDF-5）。治疗效果不存在剂量依赖性。透明质酸和bmp联合使用（单次低剂量）可大大增强绵羊腰椎骨质减少的长期骨形成和生物力学稳定性。因此，载体结合BMP的剂量比以前使用的剂量低2万至1000倍，适用于脊柱融合/骨再生，并提高了治疗安全性。
Effects of hydroxyapatite (HA) particles with bone morphogenetic BMP-2 or GDF-5 were compared in sheep lumbar osteopenia; in vitro release in phosphate-buffered saline (PBS) or sheep serum was assessed by ELISA. Lumbar (L) vertebral bone defects (Ø 3.5 mm) were generated in aged, osteopenic female sheep (n = 72; 9.00 ± 0.11 years; mean ± SEM). Treatment was: (a) HA particles (2.5 mg; L5); or (b) particles coated with BMP-2 (1 µg; 10 µg) or GDF-5 (5 µg; 50 µg; L4; all groups n = 6). Untouched vertebrae (L3) served as controls. Three and nine months post-therapy, bone formation was assessed by osteodensitometry, histomorphometry, and biomechanical testing. Cumulative 14-day BMP release was high in serum (76–100%), but max. 1.4% in PBS. In vivo induction of bone formation by HA particles with either growth factor was shown by: (i) significantly increased bone volume, trabecular and cortical thickness (overall increase HA + BMP vs. control close to the injection channel 71%, 110%, and 37%, respectively); (ii) partial significant effects for bone mineral density, bone formation, and compressive strength (increase 17%; 9 months; GDF-5). Treatment effects were not dose-dependent. Combined HA and BMPs (single low-dose) highly augment long-term bone formation and biomechanical stabilization in sheep lumbar osteopenia. Thus, carrier-bound BMP doses 20,000-fold to 1000-fold lower than previously applied appear suitable for spinal fusion/bone regeneration and improved treatment safety.
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