Peng Gordon, McNary Sean M, Athanasiou Kyriacos A, Reddi A Hari
1 Department of Orthopaedic Surgery, Lawrence Ellison Center for Tissue Regeneration and Repair, School of Medicine, University of California , Davis, Sacramento, California.
Tissue Eng Part A. 2014 Dec;20(23-24):3332-41. doi: 10.1089/ten.TEA.2014.0099.
The central hypothesis of functional tissue engineering is that an engineered construct can serve as a viable replacement tissue in vivo by replicating the structure and function of native tissue. In the case of articular cartilage, this requires the reproduction of the bulk mechanical and surface lubrication properties of native hyaline cartilage. Cartilage tissue engineering has primarily focused on achieving the bulk mechanical properties of native cartilage such as the compressive aggregate modulus and tensile strength. A scaffold-free self-assembling process has been developed that produces engineered cartilage with compressive properties approaching native tissue levels. Thus, the next step in this process is to begin addressing the friction coefficient and wear properties of these engineered constructs. The superficial zone protein (SZP), also known as lubricin or PRG4, is a boundary mode lubricant that is synthesized by surface zone (SZ) articular chondrocytes. Under conditions of high loading and low sliding speeds, SZP reduces friction and wear at the articular surface. The objective of this investigation was to determine whether increasing the proportion of SZ chondrocytes in cartilage constructs, in the absence of external stimuli such as growth factors and mechanical loading, would enhance the secretion of SZP and improve their frictional properties. In this study, cartilage constructs were engineered through a self-assembling process with varying ratios of SZ and middle zone (MZ) chondrocytes (SZ:MZ): 0:100, 25:75, 50:50, 75:25, and 100:0. Constructs containing different ratios of SZ and MZ chondrocytes did not significantly differ in the glycosaminoglycan composition or compressive aggregate modulus. In contrast, tensile properties and collagen content were enhanced in nearly all constructs containing greater amounts of SZ chondrocytes. Increasing the proportion of SZ chondrocytes had the hypothesized effect of improving the synthesis and secretion of SZP. However, increasing the SZ chondrocyte fraction did not significantly reduce the friction coefficient. These results demonstrate that additional factors, such as SZP-binding macromolecules, surface roughness, and adhesion, need to be examined to modulate the lubrication properties of engineered cartilage.
功能性组织工程的核心假说是,通过复制天然组织的结构和功能,工程构建体可在体内充当可行的替代组织。就关节软骨而言,这需要重现天然透明软骨的整体力学性能和表面润滑性能。软骨组织工程主要致力于实现天然软骨的整体力学性能,如压缩聚集模量和拉伸强度。现已开发出一种无支架自组装工艺,可生产出压缩性能接近天然组织水平的工程软骨。因此,此过程的下一步是开始研究这些工程构建体的摩擦系数和磨损特性。表面区蛋白(SZP),也称为润滑素或PRG4,是一种由表面区(SZ)关节软骨细胞合成的边界模式润滑剂。在高负荷和低滑动速度条件下,SZP可降低关节表面的摩擦和磨损。本研究的目的是确定在不存在生长因子和机械负荷等外部刺激的情况下,增加软骨构建体中SZ软骨细胞的比例是否会增强SZP的分泌并改善其摩擦性能。在本研究中,通过自组装工艺构建软骨构建体,其中SZ和中间区(MZ)软骨细胞的比例各不相同(SZ:MZ):0:100、25:75、50:50、75:25和100:0。含有不同比例SZ和MZ软骨细胞的构建体在糖胺聚糖组成或压缩聚集模量方面没有显著差异。相比之下,几乎所有含有更多SZ软骨细胞的构建体的拉伸性能和胶原蛋白含量都有所提高。增加SZ软骨细胞的比例具有改善SZP合成和分泌的预期效果。然而,增加SZ软骨细胞比例并未显著降低摩擦系数。这些结果表明,需要研究其他因素,如SZP结合大分子、表面粗糙度和粘附力,以调节工程软骨的润滑性能。