Instabilities induced by mechanical loading determine the viability of chondrocytes grown on porous scaffolds
Instabilities induced by mechanical loading determine the viability of chondrocytes grown on porous scaffolds
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机械负载引起的不稳定性决定了多孔支架上生长的软骨细胞的活力
DOI：
10.1016/j.jbiomech.2023.111591
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发表时间：
2023
影响因子：
2.4
通讯作者：
Bonassar, Lawrence J.
中科院分区：
文献类型：
--
作者：
Kim, Byumsu;Bouklas, Nikolaos;Cohen, Itai;Bonassar, Lawrence J.
组织工程软骨结构在多项临床研究中显示出治疗局灶性软骨缺陷的前景。值得注意的是，临床使用或后期临床试验中的产品通常利用多孔胶原支架为软骨细胞提供机械支撑和附着位点。尽管胶原蛋白支架用途广泛，但在载荷作用下，其局部机械反应和相应的细胞结果却知之甚少。因此，组织工程软骨产品中胶原蛋白支架的结构差异很大，但这种结构对结构力学和细胞活力的影响尚不清楚。这项研究研究了胶原支架局部机械反应对组织工程软骨结构中软骨细胞活力的影响。我们利用快速共焦显微镜结合应变图技术来分析蜂窝和海绵支架中准静态负载下的结构依赖性不稳定性以及随后的软骨细胞死亡。更具体地说，我们比较了每种类型的胶原支架的各向同性和正交各向异性平面。在压缩下，两个平面都表现出弹性、屈曲和致密变形模式。在两个加载方向上，在经历弹性变形模式和屈曲模式增加趋势的区域中，细胞死亡最少。更有趣的是，我们看到致密模式下细胞死亡显着增加。总体而言，这项研究表明，局部不稳定性与组织工程软骨结构中的软骨细胞死亡直接相关，强调了了解负载下结构依赖性局部机械响应的重要性。
Tissue-engineered cartilage constructs have shown promise to treat focal cartilage defects in multiple clinical studies. Notably, products in clinical use or in late-stage clinical trials often utilize porous collagen scaffolds to provide mechanical support and attachment sites for chondrocytes. Under loading, both the local mechanical responses of collagen scaffolds and the corresponding cellular outcomes are poorly understood, despite their wide use. As such, the architecture of collagen scaffolds varies significantly among tissue-engineered cartilage products, but the effects of such architectures on construct mechanics and cell viability are not well understood. This study investigated the effects of local mechanical responses of collagen scaffolds on chondrocyte viability in tissue-engineered cartilage constructs. We utilized fast confocal microscopy combined with a strain mapping technique to analyze the architecture-dependent instabilities under quasi-static loading and subsequent chondrocyte death in honeycomb and sponge scaffolds. More specifically, we compared the isotropic and the orthotropic planes for each type of collagen scaffold. Under compression, both planes exhibited elastic, buckled, and densified deformation modes. In both loading directions, cell death was minimal in regions that experienced elastic deformation mode and a trend of increase in buckled mode. More interestingly, we saw a significant increase in cell death in densified mode. Overall, this study suggests that local instabilities are directly correlated to chondrocyte death in tissue-engineered cartilage constructs, highlighting the importance of understanding the architecture-dependent local mechanical responses under loading.