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脂肪来源的成体干细胞在琼脂糖、藻酸盐和明胶支架中的软骨形成分化。

Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds.

作者信息

Awad Hani A, Wickham M Quinn, Leddy Holly A, Gimble Jeffrey M, Guilak Farshid

机构信息

Department of Surgery, Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

Biomaterials. 2004 Jul;25(16):3211-22. doi: 10.1016/j.biomaterials.2003.10.045.

Abstract

The differentiation and growth of adult stem cells within engineered tissue constructs are hypothesized to be influenced by cell-biomaterial interactions. In this study, we compared the chondrogenic differentiation of human adipose-derived adult stem (hADAS) cells seeded in alginate and agarose hydrogels, and porous gelatin scaffolds (Surgifoam), as well as the functional properties of tissue engineered cartilage constructs. Chondrogenic media containing transforming growth factor beta 1 significantly increased the rates of protein and proteoglycan synthesis as well as the content of DNA, sulfated glycosaminoglycans, and hydroxyproline of engineered constructs as compared to control conditions. Furthermore, chondrogenic culture conditions resulted in 86%, and 160% increases ( p < 0.05 ) in the equilibrium compressive and shear moduli of the gelatin scaffolds, although they did not affect the mechanical properties of the hydrogels over 28 days in culture. Cells encapsulated in the hydrogels exhibited a spherical cellular morphology, while cells in the gelatin scaffolds showed a more polygonal shape; however, this difference did not appear to hinder the chondrogenic differentiation of the cells. Furthermore, the equilibrium compressive and shear moduli of the gelatin scaffolds were comparable to agarose by day 28. Our results also indicated that increases in the shear moduli were significantly associated with increases in S-GAG content ( R2 = 0.36, p < 0.05 ) and with the interaction between S-GAG and hydroxyproline ( R2 = 0.34, p < 0.05 ). The findings of this study suggest that various biomaterials support the chondrogenic differentiation of hADAS cells, and that manipulating the composition of these tissue engineered constructs may have significant effects on their mechanical properties.

摘要

据推测,工程化组织构建物中成人干细胞的分化和生长受细胞与生物材料相互作用的影响。在本研究中,我们比较了接种在藻酸盐、琼脂糖水凝胶以及多孔明胶支架( Surgifoam )中的人脂肪来源成人干细胞( hADAS )的软骨形成分化,以及组织工程软骨构建物的功能特性。与对照条件相比,含有转化生长因子β1的软骨形成培养基显著提高了工程构建物的蛋白质和蛋白聚糖合成速率以及DNA、硫酸化糖胺聚糖和羟脯氨酸的含量。此外,软骨形成培养条件使明胶支架的平衡压缩模量和剪切模量分别增加了86%和160%(p < 0.05),尽管在28天的培养过程中它们并未影响水凝胶的力学性能。封装在水凝胶中的细胞呈现球形细胞形态,而明胶支架中的细胞则呈现更多边形的形状;然而,这种差异似乎并未阻碍细胞的软骨形成分化。此外,到第28天时,明胶支架的平衡压缩模量和剪切模量与琼脂糖相当。我们的结果还表明,剪切模量的增加与S - GAG含量的增加(R2 = 0.36,p < 0.05)以及S - GAG与羟脯氨酸之间的相互作用(R2 = 0.34,p < 0.05)显著相关。本研究结果表明,各种生物材料均支持hADAS细胞的软骨形成分化,并且操纵这些组织工程构建物的组成可能会对其力学性能产生显著影响。

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