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3D Tissue Engineered Supramolecular Hydrogels for Controlled Chondrogenesis of Human Mesenchymal Stem Cells

机译:3D组织工程化的超分子水凝胶可控制人间充质干细胞的软骨形成。

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Despite a wide investigation of hydrogels as an artificial extracellular matrix, there are few scaffold systems for the facile spatiotemporal control of mesenchymal stem cells (MSCs). Here, we report 3D tissue engineered supramolecular hydrogels prepared with highly water-soluble monofunctional- ized cucurbit[6]uril—hyaluronic acid (CB[6]-HA), diamino- hexane conjugated HA (DAH-HA), and drug conjugated CB[6] (drug-CB[6]) for the controlled chondrogenesis of human mesenchymal stem cells (hMSCs). The mechanical property of supramolecular HA hydrogels was modulated by changing the cross-linking density for the spatial control of hMSCs. In addition, the differentiation of hMSCs was temporally controlled by changing the release profiles of transforming growth factor-β3 (TGF-β3) and/or dexamefhasone (Dexa) from the hydrolyzable Dexa-CB[S]. The effective chondrogenic differentiation of hMSCs encapsulated in the monoCB[6]/DAH-HA hydrogel with TGF-β3 and Dexa-CB[6] was confirmed by biochemical glycosaminoglycan content analysis, real-time quantitative PCR, histological, and immunohistochemical analyses. Taken together, We could confirm the feasibility of cytocompatible monoCB[6] /DAH-HA hydrogels as a platform scaffold with controlled drug delivery for cartilage regeneration and other various tissue engineering applications.
机译:尽管对作为人工细胞外基质的水凝胶进行了广泛的研究,但很少有用于轻松控制间质干细胞(MSC)的时空支架系统。在这里,我们报道了由3D组织工程化的超分子水凝胶,其由高度水溶性的单官能化葫芦[6]尿素-透明质酸(CB [6] -HA),二氨基己烷共轭HA(DAH-HA)和药物共轭CB制备[6](drug-CB [6])用于控制人间充质干细胞(hMSCs)的软骨形成。超分子HA水凝胶的机械性能是通过改变hMSCs的交联密度来调节的。另外,通过改变转化性生长因子-β3(TGF-β3)和/或地塞米松(Dexa)从可水解Dexa-CB的释放曲线来暂时控制hMSC的分化[S]。通过生化糖胺聚糖含量分析,实时定量PCR,组织学和免疫组织化学分析,证实了具有TGF-β3和Dexa-CB [6]的monoCB [6] / DAH-HA水凝胶中封装的hMSC的有效成软骨分化。综上所述,我们可以证实细胞相容性monoCB [6] / DAH-HA水凝胶作为可控药物递送的平台支架在软骨再生和其他各种组织工程应用中的可行性。

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