Covalently tethered transforming growth factor beta in PEG hydrogels promotes chondrogenic differentiation of encapsulated human mesenchymal stem cells.
Covalently tethered transforming growth factor beta in PEG hydrogels promotes chondrogenic differentiation of encapsulated human mesenchymal stem cells.
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DOI：
10.1007/s13346-012-0090-2
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发表时间：
2012-10
影响因子：
5.4
通讯作者：
Anseth, Kristi S.
中科院分区：
文献类型：
--
作者：
McCall, Joshua D.;Luoma, Jacob E.;Anseth, Kristi S.
关键词：
以局部和持续的方式精确控制生长因子呈递的方法对于许多复杂的组织工程应用越来越感兴趣。细胞因子转化生长因子β（TGFβ）在促进人骨髓间充质干细胞（hMSCs）向软骨细胞分化中起关键作用。传统的软骨形成方法利用可溶性递送，这是一种临床转化应用有限的方法。在这项工作中，我们引入了一个反应性的硫醇到TGFβ和共价拴到聚（乙二醇）（PEG）水凝胶使用光引发的硫醇-丙烯酸酯聚合机制的生长因子。我们使用SMAD 2报告细胞系证明了聚合前后巯基化TGFβ的生物活性。将hMSC包封在具有和不具有栓系的TGFβ的PEG水凝胶中，随后测定糖胺聚糖和胶原II的产生作为软骨形成的指标。在21天的时间过程中，栓系的TGFβ以与使用可溶性剂量的生长因子的阳性对照相似的水平促进软骨形成。这些结果提供了证据表明，系留的TGFβ材料可以成功地用于促进MSC的软骨形成分化。
Methods to precisely control growth factor presentation in a local and sustained fashion are of increasing interest for a number of complex tissue engineering applications. The cytokine transforming growth factor beta (TGFβ) plays a key role in promoting the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). Traditional chondrogenic approaches utilize soluble delivery, an approach with limited application for clinical translation. In this work, we introduce a reactive thiol onto TGFβ and covalently tether the growth factor into poly(ethylene glycol) (PEG) hydrogels using a photoinitiated thiol-acrylate polymerization mechanism. We demonstrate the bioactivity of thiolated TGFβ, before and after polymerization, using a SMAD2 reporter cell line. hMSCs were encapsulated in PEG hydrogels with and without tethered TGFβ, and subsequently assayed for glycosaminoglycan and collagen II production as indicators of chondrogenesis. Over a 21-day time course, tethered TGFβ promoted chondrogenesis at levels similar to a positive control using solubly dosed growth factor. These results provide evidence that tethered TGFβ materials can be successfully used to promote chondrogenic differentiation of MSCs.
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