Program in Cellular, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.
Acta Biomater. 2013 May;9(5):6563-75. doi: 10.1016/j.actbio.2013.01.004. Epub 2013 Jan 16.
Cartilage tissue engineering aims to repair damaged cartilage tissue in arthritic joints. As arthritic joints have significantly higher levels of pro-inflammatory cytokines (such as IL-1β and TNFα that cause cartilage destruction, it is critical to engineer stable cartilage in an inflammatory environment. Biomaterial scaffolds constitute an important component of the microenvironment for chondrocytes in engineered cartilage. However, it remains unclear how the scaffold material influences the response of chondrocytes seeded in these scaffolds under inflammatory stimuli. Here we have compared the responses of articular chondrocytes seeded within three different polymeric scaffolding materials (silk, collagen and polylactic acid (PLA)) to IL-1β and TNFα. These scaffolds have different physical characteristics and yielded significant differences in the expression of genes associated with cartilage matrix production and degradation, cell adhesion and cell death. The silk and collagen scaffolds released pro-inflammatory cytokines faster and had higher uptake water abilities than PLA scaffolds. Correspondingly, chondrocytes cultured in silk and collagen scaffolds maintained higher levels of cartilage matrix than those in PLA, suggesting that these biophysical properties of scaffolds may regulate gene expression and the response to inflammatory stimuli in chondrocytes. Based on this study we conclude that selecting the proper scaffold material will aid in the engineering of more stable cartilage tissues for cartilage repair, and that silk and collagen are better scaffolds in terms of supporting the stability of three-dimensional cartilage under inflammatory conditions.
软骨组织工程旨在修复关节炎关节中受损的软骨组织。由于关节炎关节中促炎细胞因子（如 IL-1β 和 TNFα）水平显著升高，这些细胞因子会导致软骨破坏，因此在炎症环境中构建稳定的软骨至关重要。生物材料支架是工程化软骨中软骨细胞微环境的重要组成部分。然而，支架材料如何影响在炎症刺激下接种在这些支架中的软骨细胞的反应尚不清楚。在这里，我们比较了三种不同的聚合支架材料（丝、胶原和聚乳酸（PLA））中接种的关节软骨细胞对 IL-1β 和 TNFα 的反应。这些支架具有不同的物理特性，在与软骨基质产生和降解、细胞黏附和细胞死亡相关的基因表达方面存在显著差异。丝和胶原支架比 PLA 支架更快地释放促炎细胞因子，并且具有更高的吸水能力。相应地，在丝和胶原支架中培养的软骨细胞保持比 PLA 更高水平的软骨基质，这表明支架的这些生物物理特性可能调节软骨细胞中的基因表达和对炎症刺激的反应。基于这项研究，我们得出结论，选择合适的支架材料将有助于为软骨修复工程构建更稳定的软骨组织，并且丝和胶原在炎症条件下支持三维软骨稳定性方面是更好的支架。
