Freed L E, Vunjak-Novakovic G, Langer R
Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.
J Cell Biochem. 1993 Mar;51(3):257-64. doi: 10.1002/jcb.240510304.
Cartilage implants for potential use in reconstructive or orthopedic surgery can be created by growing isolated cartilage cells (chondrocytes) in vitro on synthetic, biodegradable polymer scaffolds. The scaffolds provide specific three-dimensional structures which support cell proliferation and biodegrade in a controlled fashion in parallel to cellular regeneration of cartilaginous tissue. Cartilage implants based on chondrocytes and fibrous polyglycolic acid scaffolds were recently shown to closely resemble normal cartilage histologically as well as with respect to cell density and matrix composition (collagen, glycosaminoglycan) [Freed et al., J Biomed Mater Res 27:11-23, 1993a]. These findings form the basis for developing straightforward procedures to obtain implants for clinical use from small, autologous cartilage specimens without any limitations in terms of availability of donor tissue or implant dimensions. Chondrocyte growth and cartilage matrix regeneration on polymer scaffolds are interdependent and also depend on in vitro tissue culture conditions. Under static culture conditions, cell growth rates are diffusionally limited due to increasing cell mass and decreasing effective implant porosity resulting from cartilage matrix regeneration. Optimization of the in vitro culture environment is thus essential for the cultivation of large, clinically useful cartilage implants. Preliminary studies indicate that major improvements can be achieved using bioreactors that provide efficient mass transfer and controlled shear rates at the cell and implant surfaces.
用于重建手术或整形外科手术的软骨植入物可以通过在体外将分离的软骨细胞（软骨细胞）种植在合成的、可生物降解的聚合物支架上制成。这些支架提供特定的三维结构，支持细胞增殖，并以可控的方式在软骨组织细胞再生的同时进行生物降解。最近研究表明，基于软骨细胞和纤维状聚乙醇酸支架的软骨植入物在组织学上以及细胞密度和基质组成（胶原蛋白、糖胺聚糖）方面与正常软骨非常相似[弗里德等人，《生物医学材料研究杂志》27:11 - 23，1993a]。这些发现为开发直接的程序奠定了基础，该程序可从小的自体软骨标本中获取临床使用的植入物，而在供体组织可用性或植入物尺寸方面没有任何限制。聚合物支架上的软骨细胞生长和软骨基质再生相互依存，并且还取决于体外组织培养条件。在静态培养条件下，由于细胞质量增加以及软骨基质再生导致有效植入物孔隙率降低，细胞生长速率受到扩散限制。因此，优化体外培养环境对于培养大型的、临床上有用的软骨植入物至关重要。初步研究表明，使用能够在细胞和植入物表面提供高效传质和可控剪切速率的生物反应器可以实现重大改进。
