Guo Lijia, Min Seiko, Su Yingying, Tang Jianxia, Du Juan, Goh Bee Tin, Saigo Leonardo, Wang Songlin, Ansari Sahar, Moshaverinia Alireza, Zadeh Homayoun H, Liu Yi
1 Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
2 Department of Orthodontics, Capital Medical University School of Stomatology, Beijing, China.
J Biomater Appl. 2017 Oct;32(4):425-432. doi: 10.1177/0885328217733262.
Recombinant human bone morphogenetic protein (BMP)-2 is an FDA-approved therapy for nonunion tibia fracture, though it has a number of biological and practical disadvantages. Our research group has developed a novel tissue engineering strategy termed antibody-mediated osseous regeneration. This entails application of anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMP's to mediate in vivo bone formation. This has been documented in a number of animal models. The present exploratory study sought to investigate the application of antibody-mediated osseous regeneration for repair of nonunion tibia defect in a nonhuman primate model. A 20 mm segmental osteotomy was performed in tibia of 6 Macaca fascicularis and was implanted with absorbable collagen sponge that was functionalized with chimeric anti-BMP-2 or isotype matched control mAb. Cone beam computed tomography (CBCT), histologic and histomorphometric analyses were performed 12 weeks post-operatively. CBCT analyzed by quantitative 3D volumetric analysis revealed that sites implanted with absorbable collagen sponge functionalized with anti-BMP-2 mAb demonstrated numerically higher mineralized tissue (408 ± 127 mm) compared with sites implanted with isotype matched control mAb (214 ± 81 mm), though the difference was not statistically significant ( p = 0.09). Histologic and histomorphometric analysis showed de novo bone formation with greater ( p < 0.01) percentage of bone volume in sites implanted with anti-BMP-2 (41.3 ± 4.4%), compared with isotype matched control mAb (14.6 ± 5.6%). Results from the present exploratory study provide evidence for the potential of anti-BMP-2 mAb to mediate repair of a large segmental tibia defects in a nonhuman primate model. Therapeutic antibodies have generally been shown to have great safety and efficacy profile, though their application in tissue engineering has been limited in the past. Following further investigation, anti-BMP-2 mAbs immobilized on appropriate scaffold may have application in repair of large skeletal defects without the need for exogenous growth factors.
重组人骨形态发生蛋白（BMP）-2是一种经美国食品药品监督管理局（FDA）批准用于治疗胫骨骨折不愈合的疗法，不过它存在一些生物学和实际应用方面的缺点。我们的研究小组开发了一种名为抗体介导骨再生的新型组织工程策略。这需要应用抗BMP-2单克隆抗体（mAb）来捕获内源性BMP，以介导体内骨形成。这已在多个动物模型中得到证实。本探索性研究旨在研究抗体介导骨再生在非人灵长类动物模型中修复胫骨骨折不愈合缺损的应用。在6只食蟹猴的胫骨上进行了20毫米的节段性截骨术，并植入了用嵌合抗BMP-2或同型对照mAb功能化的可吸收胶原海绵。术后12周进行锥形束计算机断层扫描（CBCT）、组织学和组织形态计量学分析。通过定量三维体积分析对CBCT进行分析发现，与植入同型对照mAb的部位（214±81毫米）相比，植入用抗BMP-2 mAb功能化的可吸收胶原海绵的部位在数值上显示出更高的矿化组织（408±127毫米），不过差异无统计学意义（p = 0.09）。组织学和组织形态计量学分析显示，与植入同型对照mAb（14.6±5.6%）相比，植入抗BMP-2的部位有新生骨形成，骨体积百分比更高（p < 0.01）（41.3±4.4%）。本探索性研究的结果为抗BMP-2 mAb在非人灵长类动物模型中介导修复大段胫骨缺损的潜力提供了证据。治疗性抗体通常已被证明具有良好的安全性和疗效，不过过去它们在组织工程中的应用一直有限。经过进一步研究，固定在合适支架上的抗BMP-2 mAb可能在无需外源性生长因子的情况下应用于修复大的骨骼缺损。
