Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-2125, USA.
Acta Biomater. 2011 Feb;7(2):505-14. doi: 10.1016/j.actbio.2010.08.027. Epub 2010 Aug 31.
The objective of this study was to evaluate the coupled effects of three-dimensional poly(1,8-octanediol-co-citrate) (POC) scaffold pore shape and permeability on chondrogenesis using primary chondrocytes in vivo. Chondrogenesis was characterized as cartilage matrix formation by sulfated glycosaminoglycan (sGAG) quantification, relative mRNA expression of the cartilage-related proteins collagen types I, II and X, aggrecan and matrix metalloproteinases 13 and 3 and the compressive mechanical properties of the tissue/scaffold construct. A low permeability design with a spherical pore shape showed a significantly greater increase in cartilage matrix formation over 6 weeks in vivo than a high permeability design with a cubical pore shape. This increase in cartilage matrix synthesis corresponded with increases in mechanical compressive nonlinear elastic properties and histological data demonstrating darker red Safranin-O staining. There was higher mRNA expression for both cartilage-specific proteins and matrix degradation proteins in the high permeability design, resulting in overall less sGAG retained in the high permeability scaffold compared with the low permeability scaffold. Controlled POC scaffolds with a spherical pore shape and low permeability correlated with significantly increased cartilage matrix production using primary seeded chondrocytes. These results indicate that the low permeability design with a spherical pore shape provided a better microenvironment for chondrogenesis than the high permeability design with a cubical pore shape. Thus, scaffold architecture and material design may have a significant impact on the success of matrix-based clinical cartilage repair strategies.
本研究旨在评估三维聚(1,8-辛二醇-柠檬酸酯)(POC)支架孔形状和渗透性对体内原代软骨细胞成软骨的偶联作用。通过硫酸化糖胺聚糖(sGAG)定量、软骨相关蛋白 I、II 和 X 型胶原、聚集蛋白和基质金属蛋白酶 13 和 3 的相对 mRNA 表达以及组织/支架构建体的压缩力学性能来表征软骨生成。与具有立方孔形状的高渗透性设计相比,低渗透性设计的球形孔形状在体内 6 周时显示出明显更大的软骨基质形成增加。这种软骨基质合成的增加与机械压缩非线性弹性特性的增加以及显示出更暗红色番红 O 染色的组织学数据相对应。高渗透性设计中,软骨特异性蛋白和基质降解蛋白的 mRNA 表达更高,导致高渗透性支架中保留的 sGAG 总体上少于低渗透性支架。具有球形孔形状和低渗透性的受控 POC 支架与使用原代接种软骨细胞的软骨基质产量显著增加相关。这些结果表明,与具有立方孔形状的高渗透性设计相比,具有球形孔形状的低渗透性设计为软骨生成提供了更好的微环境。因此,支架结构和材料设计可能对基于基质的临床软骨修复策略的成功有重大影响。