Research and Development for Fabrication of 3D-structured Tissue-engineered Cartilage through Nino-molecular Technologies

通过纳米分子技术制造 3D 结构组织工程软骨的研发

• 批准号: 16390431
• 负责人: HOSHI Kazuto
• 金额: $ 9.22万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390431/
• 关键词: nanotechnology; tissue engineering; chondrocyte; hydrogel; soluble factor; 3D culture; proliferation; differentiation

Cartilage is a major component that consists of motor and supportive tissues. Because the cartilaginous tissues suffer from various diseases and disorders including trauma, ageing diseases, inflammation and congenital anomaly, the regeneration and reconstruction of cartilage is the most important topic in the orthopaedic fields. Although the cartilage tissue engineering has gradually prevailed as autologous chondrocyte transplantation, 3D-structured tissue-engineered cartilage are needed in order to broaden the indication range of the cartilage tissue engineering for the more severe cartilage diseases such as end stage of osteoarthritis and congenital anomaly of cartilage. Otherwise, the nanotechnology has remarkably progressed, which can control the matter on a scale smaller than 1 micrometer and fabricate multipotent prolymers. In the present project, we attempted to apply the nanotechnology for the proliferation of chondrocytes in vitro and the fabrication of 3D-structured tissue-engineered cartilage.In order to prevent dedifferentiation of cultured chondrocytes, 3D culture is useful. However, the proliferation culture of chondrocytes under 3D condition had not been reported. In the present project, we attempted to use hollow fibers for the purpose of making the 3D proliferation culture system. We also investigated the combination of soluble factors that redifferentiate dedifferentiated chondrocytes, in order to solve the problem that the chondrocytes are dedifferentiated during the proliferation culture. As results, the combination of BMP-2, insulin and T3 was revealed to induce ideal redifferentiation. Moreover, we examined the novel materials including the scaffolds which synthetic peptides possess no risk of cross-contamination and the functional micelles for gene transfection.These results would provide useful information for the clinical application of cartilage tissue engineering.

腕关节是由运动组织和支持组织组成的主要组成部分。由于软骨组织遭受各种疾病和障碍，包括创伤、衰老性疾病、炎症和先天性异常，软骨的再生和重建是骨科领域最重要的课题。虽然软骨组织工程以自体软骨细胞移植的方式逐渐流行，但为了拓宽软骨组织工程对更严重的软骨疾病如终末期骨关节炎和先天性软骨异常的适应范围，需要三维结构的组织工程软骨。另外，纳米技术也取得了显著的进展，可以在小于1微米的尺度上控制物质，并制造多能性的prolymer。本课题尝试将纳米技术应用于软骨细胞的体外增殖和三维结构组织工程软骨的构建。为了防止培养软骨细胞的去分化，三维培养是有用的。然而，软骨细胞在三维条件下的增殖培养尚未见报道。在本项目中，我们尝试使用中空纤维来制作3D增殖培养系统。我们还研究了使去分化软骨细胞再分化的可溶性因子的组合，以解决软骨细胞在增殖培养过程中去分化的问题。结果显示，BMP-2、胰岛素和T3的组合诱导理想的再分化。此外，我们还对新型材料进行了研究，包括合成肽无交叉污染风险的支架材料和用于基因转染的功能性胶束，这些结果将为软骨组织工程的临床应用提供有用的信息。

项目成果

Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes

• DOI: 10.1101/gad.1224204
• 发表时间: 2004-10-01
• 期刊: GENES & DEVELOPMENT
• 影响因子: 10.5
• 作者: Chikuda, H;Kugimiya, F;Kawaguchi, H
• 通讯作者: Kawaguchi, H

バイオミネラリゼーションとそれに倣う新機能材料の創製

生物矿化和模仿生物矿化的新型功能材料的创建

• 发表时间: 2007
• 作者: Y.Sasaki;W.-J.Tian;M.Hashizume;M.Hashizume;菊池純一;橋詰峰雄;M.Otsuki;M.Hashizume;K.Matsui;W.-J.Tian;菊池純一;菊池純一
• 通讯作者: 菊池純一

Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability

• DOI: 10.1002/art.22041
• 发表时间: 2006-08-01
• 期刊: ARTHRITIS AND RHEUMATISM
• 作者: Kamekura, Satoru;Kawasaki, Yosuke;Kawaguchi, Hiroshi
• 通讯作者: Kawaguchi, Hiroshi

脱分化型軟骨細胞の軟骨細胞への再分化用培地

用于将去分化软骨细胞再分化为软骨细胞的培养基

• 发表时间: 2005

Three-dimensional microenvironments retain chondrocyte phenotypes during proliferation culture.

• DOI: 10.1089/ten.2006.0322
• 发表时间: 2007-07
• 期刊: Tissue engineering
• 作者: Tsuguharu Takahashi;T. Ogasawara;Y. Asawa;Y. Mori;E. Uchinuma;T. Takato;K. Hoshi