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首页> 外文期刊>Acta biomaterialia >An in vitro and in vivo comparison of cartilage growth in chondrocyte-laden matrix metalloproteinase-sensitive poly(ethylene glycol) hydrogels with localized transforming growth factor beta 3
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An in vitro and in vivo comparison of cartilage growth in chondrocyte-laden matrix metalloproteinase-sensitive poly(ethylene glycol) hydrogels with localized transforming growth factor beta 3

机译：软骨生长的体外和体内比较，含有局部转化生长因子β3的软骨细胞 - 升降基质金属蛋白酶敏感聚（乙二醇）水凝胶中的软骨生长

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While matrix-assisted autologous chondrocyte implantation has emerged as a promising therapy to treat focal chondral defects, matrices that support regeneration of hyaline cartilage remain challenging. The goal of this work was to investigate the potential of a matrix metalloproteinase (MMP)-sensitive poly (ethylene glycol) (PEG) hydrogel containing the tethered growth factor, transforming growth factor 113 (TGF-beta 3), and compare cartilage regeneration in vitro and in vivo. The in vitro environment comprised chemically-defined medium while the in vivo environment utilized the subcutaneous implant model in athymic mice. Porcine chondrocytes were isolated and expanded in 2D culture for 10 days prior to encapsulation. The presence of tethered TGF-beta 3 reduced cell spreading. Chondrocyte-laden hydrogels were analyzed for total sulfated glycosaminoglycan and collagen contents, MMP activity, and spatial deposition of aggrecan, decorin, biglycan, and collagens type II and I. The total amount of extracellular matrix (ECM) deposited in the hydrogel constructs was similar in vitro and in vivo. However, the in vitro environment was not able to support long-term culture up to 64 days of the engineered cartilage leading to the eventual breakdown of aggrecan. The in vivo environment, on the other hand, led to more elaborate ECM, which correlated with higher MMP activity, and an overall higher quality of engineered tissue that was rich in aggrecan, decorin, biglycan and collagen type II with minimal collagen type I. Overall, the MMPsensitive PEG hydrogel containing tethered TGF-beta 3 is a promising matrix for hyaline cartilage regeneration in vivo.
机译：虽然基质辅助的自体软骨细胞植入植入作为治疗局灶性骨质缺陷的有希望的疗法，但支持透明软骨再生的基质仍然具有挑战性。本作作品的目的是研究含有束缚生长因子的基质金属蛋白酶（MMP） - 敏感聚（乙二醇）（PEG）水凝胶的潜力，转化生长因子113（TGF-β3），并比较软骨再生体外和体内。体外环境包括化学定义的培养基，而体内环境在无胸腺小鼠中使用皮下植入模型。在包封之前将猪软骨细胞分离并在2D培养物中膨胀10天。束缚TGF-β3的存在降低了细胞扩散。分析软骨细胞 - 升起水凝胶，用于总硫酸化糖胺糖苷和胶原蛋白含量，MMP活性和蛋白质，Qualin，Biglycan和胶原蛋白的空间沉积和I型和I。水凝胶构建体中沉积的细胞外基质（ECM）的总量相似体外和体内。然而，体外环境无法支持长期培养，长达64天的工程软件，导致聚会的最终崩溃。另一方面，体内环境导致更细心的ECM，其与较高的MMP活性相关，以及具有富含蛋白质，装饰汀类，大葡萄酒和胶原蛋白II型富含胶原蛋白，胶原蛋白的工程组织的整体更高质量的工程组织。总的来说，含有系环化TGF-β3的MM敏感PEG水凝胶是体内透明软骨再生的有望基质。

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