Freed L E, Marquis J C, Nohria A, Emmanual J, Mikos A G, Langer R
Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139.
J Biomed Mater Res. 1993 Jan;27(1):11-23. doi: 10.1002/jbm.820270104.
Cartilaginous implants for potential use in reconstructive or orthopedic surgery were created using chondrocytes grown on synthetic, biodegradable polymer scaffolds. Chondrocytes isolated from bovine or human articular or costal cartilage were cultured on fibrous polyglycolic acid (PGA) and porous poly(L)lactic acid (PLLA) and used in parallel in vitro and in vivo studies. Samples were taken at timed intervals for assessment of cell number and cartilage matrix (sulfated glycosaminoglycan [S-GAG], collagen). The chondrocytes secreted cartilage matrix to fill the void spaces in the polymer scaffolds that were simultaneously biodegrading. In vitro, chondrocytes grown on PGA for 6 weeks reached a cell density of 5.2 x 10(7) cells/g, which was 8.3-fold higher than at day 1, and equalled the cellularity of normal bovine articular cartilage. In vitro, the cell growth rate was approximately twice as high on PGA as it was on PLLA; cells grown on PGA produced S-GAG at a high steady rate, while cells grown on PLLA produced only minimal amounts of S-GAG. These differences could be attributed to polymer geometry and biodegradation rate. In vivo, chondrocytes grown on both PGA and PLLA for 1-6 months maintained the three-dimensional (3-D) shapes of the original polymer scaffolds, appeared glistening white macroscopically, contained S-GAG and type II collagen, and closely resembled cartilage histologically. These studies demonstrate the feasibility of culturing isolated chondrocytes on biodegradable polymer scaffolds to regenerate 3-D neocartilage.
用于重建或矫形外科手术的软骨植入物是利用在合成的、可生物降解的聚合物支架上生长的软骨细胞制成的。从牛或人的关节软骨或肋软骨中分离出的软骨细胞在纤维状聚乙醇酸（PGA）和多孔聚（L）乳酸（PLLA）上进行培养，并同时用于体外和体内研究。在特定时间间隔取样，以评估细胞数量和软骨基质（硫酸化糖胺聚糖[S-GAG]、胶原蛋白）。软骨细胞分泌软骨基质以填充聚合物支架中同时发生生物降解的空隙。在体外，在PGA上培养6周的软骨细胞达到了5.2×10⁷个细胞/克的细胞密度，这比第1天高出8.3倍，并且与正常牛关节软骨的细胞密度相当。在体外，PGA上的细胞生长速率大约是PLLA上的两倍；在PGA上生长的细胞以高稳定速率产生S-GAG，而在PLLA上生长的细胞仅产生极少量的S-GAG。这些差异可归因于聚合物的几何形状和生物降解速率。在体内，在PGA和PLLA上培养1至6个月的软骨细胞保持了原始聚合物支架的三维（3-D）形状，宏观上呈现闪亮的白色，含有S-GAG和II型胶原蛋白，并且在组织学上与软骨非常相似。这些研究证明了在可生物降解的聚合物支架上培养分离的软骨细胞以再生3-D新软骨的可行性。
