Division of Biomedical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, SK S7N 5A9, Canada.
Department of Mechanical Engineering, College of Engineering, University of Saskatchewan, Saskatoon, SK S7N 5A9, Canada.
Int J Mol Sci. 2023 Apr 18;24(8):7410. doi: 10.3390/ijms24087410.
The goal of cartilage tissue engineering (CTE) is to regenerate new hyaline cartilage in joints and treat osteoarthritis (OA) using cell-impregnated hydrogel constructs. However, the production of an extracellular matrix (ECM) made of fibrocartilage is a potential outcome within hydrogel constructs when in vivo. Unfortunately, this fibrocartilage ECM has inferior biological and mechanical properties when compared to native hyaline cartilage. It was hypothesized that compressive forces stimulate fibrocartilage development by increasing production of collagen type 1 (Col1), an ECM protein found in fibrocartilage. To test the hypothesis, 3-dimensional (3D)-bioprinted hydrogel constructs were fabricated from alginate hydrogel impregnated with ATDC5 cells (a chondrogenic cell line). A bioreactor was used to simulate different in vivo joint movements by varying the magnitude of compressive strains and compare them with a control group that was not loaded. Chondrogenic differentiation of the cells in loaded and unloaded conditions was confirmed by deposition of cartilage specific molecules including glycosaminoglycans (GAGs) and collagen type 2 (Col2). By performing biochemical assays, the production of GAGs and total collagen was also confirmed, and their contents were quantitated in unloaded and loaded conditions. Furthermore, Col1 vs. Col2 depositions were assessed at different compressive strains, and hyaline-like cartilage vs. fibrocartilage-like ECM production was analyzed to investigate how applied compressive strain affects the type of cartilage formed. These assessments showed that fibrocartilage-like ECM production tended to reduce with increasing compressive strain, though its production peaked at a higher compressive strain. According to these results, the magnitude of applied compressive strain governs the production of hyaline-like cartilage vs. fibrocartilage-like ECM and a high compressive strain stimulates fibrocartilage-like ECM formation rather than hyaline cartilage, which needs to be addressed by CTE approaches.
软骨组织工程（CTE）的目标是利用细胞浸渍水凝胶构建体在关节中再生新的透明软骨并治疗骨关节炎（OA）。然而，在体内时，水凝胶构建体中可能会产生由纤维软骨组成的细胞外基质（ECM）。不幸的是，与天然透明软骨相比，这种纤维软骨 ECM 的生物学和机械性能较差。假设压缩力通过增加胶原蛋白 1（Col1）的产生来刺激纤维软骨的发育，Col1 是纤维软骨中发现的一种 ECM 蛋白。为了验证这一假设，使用海藻酸钠水凝胶（一种可生物降解的聚合物）来制造了 3D 生物打印的水凝胶构建体，该水凝胶中浸渍有 ATDC5 细胞（一种软骨细胞系）。生物反应器用于通过改变压缩应变的幅度来模拟不同的体内关节运动，并将其与未加载的对照组进行比较。在加载和未加载条件下，通过沉积软骨特异性分子（包括糖胺聚糖（GAGs）和胶原蛋白 2（Col2））证实了细胞的软骨分化。通过进行生化分析，还证实了 GAGs 和总胶原的产生，并在未加载和加载条件下对其含量进行了定量。此外，在不同的压缩应变下评估了 Col1 与 Col2 的沉积，并分析了透明软骨样 ECM 与纤维软骨样 ECM 的产生，以研究施加的压缩应变如何影响形成的软骨类型。这些评估表明，纤维软骨样 ECM 的产生随着压缩应变的增加而趋于减少，尽管其产生在较高的压缩应变下达到峰值。根据这些结果，施加的压缩应变的大小决定了透明软骨样 ECM 与纤维软骨样 ECM 的产生，高压缩应变刺激纤维软骨样 ECM 的形成而不是透明软骨，这需要通过 CTE 方法来解决。
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