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

开发用于关节成形术的新型假体，并具有使用骨形态发生蛋白 (BMP) 促进骨修复的附加能力

• 批准号: 14370459
• 负责人: SAITO Naoto
• 金额: $ 8.77万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14370459/
• 关键词: bone morphogenetic protein; prosthesis for arthroplasty; bone tissue repair; drug delivery system; biomaterial; cytokine; mononuclear cell; biodegradable polymer; 骨欠損; ドラッグデリバリーシステム; 骨組織再生; 再生医療; 組織再生; デリバリーシステム; 組織工学; 担体

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.

为了开发用于关节成形术的新型假体，并具有使用骨形态发生蛋白 (BMP) 促进骨修复的附加能力，我们首先使用可生物降解的聚合物 PLA-DX-PEG 开发了一种安全的新型 BMP 输送系统。这种聚合物适合掺入 BMP 并构建假肢装置。然后，用这种 BMP/PLA-DX-PEG 复合材料构建的假体在动物模型中进行髋关节置换实验，以证实该装置的实用性。然而，这种含有BMP的假体在临床应用之前，与BMP本身相关的许多问题仍有待解决。在人类中，少量 BMP 无法形成足够的骨形成，因此需要大量 BMP。然而，BMP 价格昂贵。为了解决这个问题，我们研究了PTH或己酮可可碱的应用，两者都可以提高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。我们开发的新型假体材料显示出对骨骼的高亲和力，并且具有利用 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成分，以便将这种新材料有效地融入到含有BMP的假体中。从提高BMP促进骨修复的能力到开发构建假体的新材料，我们开发了一种新型关节置换假肢的通用技术，并增加了利用BMP促进骨修复的能力。我们认为有必要推动更多方向的 BMP 临床应用。

项目成果

Takahashi J, Saito N, et al.: "Anterior thoracic spinal fusion in dogs by injection of recombinant human bone morphogenetic-2 and a synthetic polymer"J Spinal Disord. 16. 137-143 (2003)

Takahashi J、Saito N 等人：“通过注射重组人骨形态发生 2 和合成聚合物对狗进行前胸椎融合”J Spinal Disord。

Horiuchi H, Saito N, et al.: "Enhancement of recombinant human bone morphogenetic protein-2 (rhbmp-2) in duced new bone formation by concurrent treatment with parathyroid hormone and a phosphodiesterase inhibitor, pentoxifylline"J Bone Miner Metab. (in pr

Horiuchi H、Saito N 等人：“通过甲状旁腺激素和磷酸二酯酶抑制剂己酮可可碱同时治疗，重组人骨形态发生蛋白 2 (rhbmp-2) 在诱导新骨形成中的增强”J Bone Miner Metab。

Ohta H, Kobayashi S, Saito N, Nawata M, Horiuchi H, Takaoka K: "Sequential changes in periprosthetic bone mineral density following total hip arthroplasty : A 3-year follow-up"Bone Miner Metab. (in press).

Ohta H、Kobayashi S、Saito N、Nawata M、Horiuchi H、Takaoka K：“全髋关节置换术后假体周围骨矿物质密度的连续变化：3 年随访”Bone Miner Metab。

Horiuchi H, Saito N, Kinoshita T, Wakabayashi S, Yotsumoto N, Takaoka K: "Effect of phosphodiesterase inhibitor 4, rolipram, on new bone formations by recombinant human bone morphogenetic protein-2"Bone. 30. 589-593 (2002)

Horiuchi H、Saito N、Kinoshita T、Wakabayashi S、Yotsumoto N、Takaoka K：“磷酸二酯酶抑制剂 4 咯利普兰对重组人骨形态发生蛋白 2 形成新骨的影响”骨。

Saito N, Horiuchi H, Murakami N, Takahashi J, Okada T, Nozaki K, Takaoka K: "New synthetic biodegradable polymers for bone morphogenetic protein delivery systems. In"Biomaterials handbook : advanced applications of basic sciences and bioengineering"(Ed.)

Saito N、Horiuchi H、Murakami N、Takahashi J、Okada T、Nozaki K、Takaoka K：“用于骨形态发生蛋白递送系统的新型合成生物可降解聚合物。在《生物材料手册：基础科学和生物工程的高级应用》（编辑）