Development of new prostheses for arthroplasty with an added ability to promote bone repair using bone morphogenetic protein (BMP)

为了开发新的关节置换术假体，增加使用骨形态发生蛋白（BMP）促进骨修复的能力，我们首先使用PLA-DX-PEG（一种可生物降解的聚合物）开发了一种安全的新型BMP递送系统。该聚合物适合于掺入BMP并构建假体装置。然后将由该BMP/PLA-DX-PEG复合物构建的假体用于动物模型中的实验性髋关节置换，以确认该装置的有用性。然而，在这种含BMP的假体临床应用之前，与BMP本身相关的许多问题仍有待解决。在人类中，用少量BMP获得的骨形成不足，这使得需要大量BMP。然而，BMP是昂贵的。为了解决这一问题，我们研究了甲状旁腺素（PTH）或戊茶碱（pentaphylline）的应用，这两种药物都可以提高BMP的骨诱导能力。接下来，我们尝试骨髓单核细胞移植来改善骨修复区域周围组织的血流。我们开发的新假体材料显示出对骨骼的高亲和力，并且具有使用BMP改善骨骼修复的强大能力。目前正在研究传统假体材料和这种新材料的组成，以便将这种新材料有效地结合到含有BMP的假体中。从改善BMP促进骨修复的能力到开发构建假体的新材料，我们开发了一种用于关节成形术的新假体的通用技术，具有使用BMP促进骨修复的额外能力。我们认为有必要促进BMP临床应用的更多方向的方法。

In order to developing new prostheses for arthroplasty with an added ability to promote bone repair using bone morphogenetic protein (BMP), we first developed a safe new BMP delivery system using PLA-DX-PEG, a biodegradable polymer. This polymer is suitable for incorporating BMP and constructing a prosthetic device. The prosthesis constructed from this BMP/PLA-DX-PEG composite was then used for experimental hip replacement in an animal model to confirm the usefulness of this device. However, many problems related to BMP itself remain to be resolved before clinical application of this prosthesis containing BMP. In humans, insufficient bone formation is obtained with small volumes of BMP, which makes a large quantity of BMP necessary. However, BMP is expensive. To resolve this problem, we studied the application of PTH or pentoxifylline, either of which can improve the bone induction ability of BMP. Next, we tried bone marrow mononuclear cell transplantation to improve blood flow in tissue surrounding the area undergoing bone repair. The new prosthetic material that we developed showed a high affinity to bone, and a potent ability to improve bone repair using BMP. The compositions of conventional prosthetic materials and this new material are currently being studied in order for this new material to be effectively incorporated into a prosthesis containing BMP. From improving the ability of BMP to promote bone repair to the development of new materials to construct the prosthesis, we developed a general technology for new prostheses for arthroplasty with an added ability to promote bone repair using BMP. We consider it necessary to promote more multidirectional approaches to the clinical application of BMP.