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Evaluation of Cell-Laden Polyelectrolyte Hydrogels Incorporating Poly(L-Lysine) for Applications in Cartilage Tissue Engineering

机译:含聚L-赖氨酸的载有细胞的聚电解质水凝胶在软骨组织工程中的应用评价

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摘要

To address the lack of reliable long-term solutions for cartilage injuries, strategies in tissue engineering are beginning to leverage developmental processes to spur tissue regeneration. This study focuses on the use of poly(L-lysine) (PLL), previously shown to up-regulate mesenchymal condensation during developmental skeletogenesis in vitro, as an early chondrogenic stimulant of mesenchymal stem cells (MSCs). We characterized the effect of PLL incorporation on the swelling and degradation of oligo(poly(ethylene) glycol) fumarate) (OPF)-based hydrogels as functions of PLL molecular weight and dosage. Furthermore, we investigated the effect of PLL incorporation on the chondrogenic gene expression of hydrogel-encapsulated MSCs. The incorporation of PLL resulted in early enhancements of type II collagen and aggrecan gene expression and type II/type I collagen expression ratios when compared to blank controls. The presentation of PLL to MSCs encapsulated in OPF hydrogels also enhanced N-cadherin gene expression under certain culture conditions, suggesting that PLL may induce the expression of condensation markers in synthetic hydrogel systems. In summary, PLL can function as an inductive factor that primes the cellular microenvironment for early chondrogenic gene expression but may require additional biochemical factors for the generation of fully functional chondrocytes.
机译:为了解决软骨损伤缺乏可靠的长期解决方案的问题,组织工程学中的策略开始利用发展过程来刺激组织再生。这项研究专注于聚(L-赖氨酸)(PLL)的使用,以前证明其在体外骨骼发育过程中会上调间充质凝结,作为间充质干细胞(MSC)的早期软骨刺激性物质。我们表征了PLL掺入对基于寡聚(聚(乙二醇)富马酸酯)(OPF)的水凝胶的溶胀和降解的影响,这是PLL分子量和剂量的函数。此外,我们研究了PLL掺入对水凝胶包裹的MSC软骨形成基因表达的影响。与空白对照相比,PLL的掺入导致II型胶原蛋白和聚集蛋白聚糖基因表达以及II / I型胶原蛋白表达比率的早期增强。在某些培养条件下,PLL向包裹在OPF水凝胶中的MSC的呈递也增强了N-钙粘蛋白基因的表达,这表明PLL可能诱导合成水凝胶系统中缩合标志物的表达。总而言之,PLL可以充当诱导因子,为早期软骨生成基因的表达引发细胞微环境,但可能需要其他生化因子来生成功能完整的软骨细胞。

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