Department of Materials Science and Engineering, College of Engineering, Drexel University, Philadelphia, Pennsylvania.
College of Medicine, Drexel University, Philadelphia, Pennsylvania.
J Biomed Mater Res A. 2019 Sep;107(9):1977-1987. doi: 10.1002/jbm.a.36710. Epub 2019 May 22.
Biomimetic proteoglycan (BPG) diffusion into articular cartilage has the potential to restore the lost proteoglycan content in osteoarthritic cartilage given these molecules mimic the structure and properties of natural proteoglycans. We examined the diffusion characteristics of BPGs through cartilage with the use of a custom-made in vitro cartilage diffusion model in both normal bovine and human osteoarthritic cartilage explants. BPGs were introduced into the cartilage through essentially one-dimensional diffusion using osteochondral plugs. The molecular diffusion was shown to be size and concentration dependent. Diffusion profiles were found over different diffusion time intervals and the profiles were fit to a nonlinear Fickian diffusion model. Steady state 011012-7diffusion coefficients for BPGs were found to be 4.01 and 3.53 μm /s for 180 and 1600 kDa BPGs, respectfully, and these values are similar to other large molecule diffusion in cartilage. In both bovine and osteoarthritic human cartilage, BPGs were found localized around the chondrocytes. BPG localization was examined by labeling collagen type VI and soaking 5 μm thick sections of cartilage with BPG solutions demonstrating that the BPGs diffused into the cartilage and preferentially localized alongside collagen type VI in the pericellular matrix.
仿生蛋白聚糖 (BPG) 能够扩散到关节软骨中,有可能恢复骨关节炎软骨中丢失的蛋白聚糖含量,因为这些分子模拟了天然蛋白聚糖的结构和特性。我们使用定制的体外软骨扩散模型研究了 BPG 在正常牛和人骨关节炎软骨外植体中的扩散特性。BPG 通过使用骨软骨塞进行基本上一维的扩散引入软骨中。结果表明,分子扩散与分子大小和浓度有关。在不同的扩散时间间隔内发现了扩散曲线,并将这些曲线拟合到非线性菲克扩散模型中。发现 180 和 1600 kDa 的 BPG 的稳态扩散系数分别为 4.01 和 3.53 μm/s,这些值与软骨中其他大分子的扩散相似。在牛和骨关节炎人软骨中,BPG 都被发现定位于软骨细胞周围。通过标记胶原 VI 并将 5 μm 厚的软骨切片浸泡在 BPG 溶液中检查 BPG 的定位,证明 BPG 扩散到软骨中,并优先与细胞外基质中的胶原 VI 一起定位。