Huang Tse-Yin, Wu Chang-Chin, Weng Pei-Wei, Chen Jian-Ming, Yeh Weng-Ling
Ph.D. Program for Biotech Pharmaceutical Industry, School of Pharmacy, China Medical University, Taichung 40402, Taiwan.
Department of Orthopedics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
Bone Rep. 2020 Dec 10;14:100739. doi: 10.1016/j.bonr.2020.100739. eCollection 2021 Jun.
Autografts, the gold standard treatment for large bone defects, present complications, especially in conditions with reduced bone-repair capacity, such as osteoporosis. -derived recombinant human bone morphogenesis protein-2 (ErhBMP-2), was used in this study to improve the osteoinductivity of β-tricalcium phosphate (β-TCP). This study evaluated the bone-repair capacity of ErhBMP-2-loaded β-TCP on osteoporosis rabbit model, relative to the sole use of autograft and β-TCP treatments.
The osteoporosis rabbit model was induced through ovariectomy and glucocorticoid dosing; 2-cm segmental ulnar defects were created, which were treated with either autograft, β-TCP alone, or ErhBMP-2-loaded β-TCP or left untreated. The quality of newly formed ulnae was evaluated 8 weeks after ulnar surgery through micro-CT, biomechanical, histological, and histomorphometric assessments.
The osteoporosis rabbit model was developed and maintained till the end of the study. The maximal load and stiffness in the ErhBMP-2-loaded TCP group were significantly higher than those in the autograft group, whereas the TCP-alone group performed similarly as did the untreated group in the force loading and stiffness tests. According to the micro-CT evaluation, the ErhBMP-2-loaded TCP group had significantly higher bone volume relative to the autograft and TCP-alone groups. Histological assessments revealed better defect bridging and marrow formation in the ErhBMP-2-loaded TCP group relative to the TCP-alone group. Mineral apposition rates were significantly higher in the ErhBMP-2-loaded TCP and autograft groups than in the TCP-alone and untreated groups.
Relative to autografts, ErhBMP-2-loaded TCP, as an alternative grafting material, provides better or comparable healing on critical-sized long bone defects in the osteoporosis rabbit model.
自体骨移植是治疗大骨缺损的金标准疗法,但存在并发症,尤其是在骨修复能力降低的情况下,如骨质疏松症。本研究使用人源重组骨形态发生蛋白-2(ErhBMP-2)来提高β-磷酸三钙(β-TCP)的骨诱导活性。本研究评估了负载ErhBMP-2的β-TCP在骨质疏松兔模型上的骨修复能力,并与单纯使用自体骨移植和β-TCP治疗进行比较。
通过卵巢切除术和给予糖皮质激素诱导建立骨质疏松兔模型;制造2厘米的尺骨节段性缺损,分别用自体骨移植、单纯β-TCP、负载ErhBMP-2的β-TCP治疗或不进行治疗。尺骨手术后8周,通过微型计算机断层扫描(micro-CT)、生物力学、组织学和组织形态计量学评估来评价新形成尺骨的质量。
成功建立并维持骨质疏松兔模型直至研究结束。负载ErhBMP-2的TCP组的最大负荷和刚度显著高于自体骨移植组,而单纯TCP组在力加载和刚度测试中的表现与未治疗组相似。根据micro-CT评估,负载ErhBMP-2的TCP组的骨体积相对于自体骨移植组和单纯TCP组显著更高。组织学评估显示,相对于单纯TCP组,负载ErhBMP-2的TCP组的缺损桥接和骨髓形成更好。负载ErhBMP-2的TCP组和自体骨移植组的矿物质沉积率显著高于单纯TCP组和未治疗组。
相对于自体骨移植,负载ErhBMP-2的TCP作为一种替代移植材料,在骨质疏松兔模型的临界尺寸长骨缺损修复中能提供更好或相当的愈合效果。