Department of Cartilage & Bone Regeneration (Fujisoft), Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, Japan.
Biomaterials. 2010 Jun;31(16):4506-16. doi: 10.1016/j.biomaterials.2010.02.028. Epub 2010 Mar 4.
To broaden the clinical application of cartilage regenerative medicine, we should develop an implant-type tissue-engineered cartilage with firmness and 3-D structure. For that, we attempted to use a porous biodegradable polymer scaffold in the combination with atelocollagen hydrogel, and optimized the structure and composition of porous scaffold. We administered chondrocytes/atelocollagen mixture into the scaffolds with various kinds of porosities (80-95%) and pore sizes (0.3-2.0 mm), consisting of PLLA or related polymers (PDLA, PLA/CL and PLGA), and transplanted the constructs in the subcutaneous areas of nude mice. The constructs using scaffolds of excessively large pore sizes (>1 mm) broke out on the skin and impaired the host tissue. The scaffold with the porosity of 95% and pore size of 0.3 mm could effectively retain the cells/gel mixture and indicated a fair cartilage regeneration. Regarding the composition, the tissue-engineered cartilage was superior in PLGA and PLLA to that in PLA/CA and PDLA. The latter two showed the dense accumulation of macrophages, which may deteriorate the cartilage regeneration. Although PLGA or PLLA has been currently recommended for the scaffold of cartilage, the polymer for which biodegradation was exactly synchronized to the cartilage regeneration would improve the quality of the tissue-engineered cartilage.
为了拓宽软骨再生医学的临床应用范围，我们应该开发具有一定硬度和三维结构的植入式组织工程软骨。为此，我们尝试将多孔可生物降解聚合物支架与纤维蛋白胶相结合，并优化了多孔支架的结构和组成。我们将软骨细胞/纤维蛋白胶混合物注入到具有不同孔隙率（80-95%）和孔径（0.3-2.0 毫米）的多孔支架中，这些支架由 PLLA 或相关聚合物（PDLA、PLA/CL 和 PLGA）组成，并将构建体移植到裸鼠的皮下区域。使用孔径过大（>1 毫米）的支架构建体在皮肤表面破裂，并损害了宿主组织。孔隙率为 95%、孔径为 0.3 毫米的支架可以有效地保留细胞/凝胶混合物，并显示出良好的软骨再生效果。关于组成，与 PLA/CA 和 PDLA 相比，组织工程软骨在 PLGA 和 PLLA 中的表现更为优异。后两种材料显示出大量巨噬细胞的密集聚集，这可能会恶化软骨再生。虽然目前推荐使用 PLGA 或 PLLA 作为软骨支架的材料，但如果能使聚合物的生物降解与软骨再生精确同步，将提高组织工程软骨的质量。
