Computer aided skeletal reconstruction with use of Bone Morphogenetic Protein -Experimental study of new method for skeletal reconstructive surgery-

由于手术切除骨、软组织肿瘤或高能损伤，在临床实践中经常遇到不同部位、不同大小和形状的大骨缺损的重建。然而，目前修复大骨缺损的方式还不够，临床结果通常不令人满意，即使使用自体骨移植。因此，迫切需要在短时间内高效、准确地修复大面积骨缺损的新方法。本研究旨在利用DNA重组技术产生的生物活性蛋白（骨形态发生蛋白-2，BMP-2）、合成生物材料（HA，羟基磷灰石）、合成聚合物（聚乳酸-聚乙二醇嵌段共聚物，PLA-PEG）和可生物降解的β磷酸三钙（β tcp）粉末，共同开发促进骨修复的新技术。作为临床前研究，我们制作了犬骨盆骨缺损模型，其中可选的缺损部位为1 ..更多地生成了髂骨，并根据计算机断层扫描数据，从对侧正常髂骨的镜像图像中减去受影响髂骨的三维图像，确定了真实大小和形状的骨缺损。利用骨缺损的三维CT数据，利用计算机辅助设计（CAD）系统制作与骨缺损完全相同的HA种植体，将CAD制作的HA种植体与BMP、PLA-PEG聚合物和βTCP粉末结合，将小剂量BMP-2 （-100 μg）混合到膏状的PLA-PEG聚合物/ βTCP粉末中。（分别为~ 100mg），涂覆在HA种植体表面，通过外科手术植入骨缺损。术后每周进行骨盆常规和CT扫描，观察成骨反应。术后3周开始出现覆盖种植体的新骨，术后9周完全覆盖整个种植体。术后9周取下的髂骨肉眼可见，原有骨缺损完全修复，新骨形成，髂骨解剖恢复正常。结果表明，复合材料（重组BMP-2、PLA-PGE聚合物βTCP和Hablock）可在短时间内修复大面积骨缺损，无需植骨。少

Reconstruction of large bone defects at various site with various size and shape are often encountered in clinical practice as results from surgical resection of bone and for soft tissue tumors or from the high energy injury. However, current modalities to repair the large bone defects are not enough and clinical outcomes are usually not satisfactory, even if with use of autogenous bone grafting. And novel methods to repair such large bone defects with high efficacy and accuracy in short periods are urged. This study is aiming at development of such a new technology to promote bone repair with combined use of a bioactive protein (bone morphogenetic protein-2, BMP-2) produced by DNA recombination technology, synthetic biomaterial (HA, hydroxyapatite) a synthetic polymer (polylactic acid-polyethylene glycol block co-polymer, PLA-PEG) and a biodegradable β tricalcium phosphate (βTCP) powder. As a preclinical study, we generated a pelvic bone defect model in dog, where optional defect in t … More he iliac bone was generated and the real-sized and shaped bone defect was determined based on computer tomography scanning data by subtracting the three-dimensional image of the affected iliac bone from mirror-imaged contralateral normal ilium. The 3-dimensional CT data of the bone defect was utilized to fabricate HA implant correctively identical to the bone defect by a computer aided designing (CAD) system Tb combine the CAD fabricated HA implant with BMP, PLA-PEG polymer and βTCP powder, small dose of BMP-2 (-100 μg) was mixed into paste-natured PLA-PEG polymer/ βTCP powder. (〜100mg respectively) and coated the HA implant surface and placed into the bone defect by surgical procedures. After surgery, the bone forming reactions were followed weekly by routine and CT scanning radiographyof the pelvis. New bone covering the implant started to appear in 3 weeks after surgery and completely covered whole implant in 9 weeks, On gross appearance of the retreaved ilium at 9 weeks after surgery, the original bone defect was completely repaired with new bone formation and restored normal anatomy of the ilium. The results indicated potential repair of large bone defects with use of synthetic materials (recombinant BMP-2, PLA-PGE polymer βTCP and Hablock) without use of bone grafting in short periods of time. Less