Department of Chemical and Biological Engineering, University of Colorado at Boulder, Boulder, CO USA.
Drug Deliv Transl Res. 2012 Oct;2(5):305-12. doi: 10.1007/s13346-012-0090-2. Epub 2012 Sep 18.
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.
精确控制生长因子局部和持续呈现的方法对于许多复杂的组织工程应用越来越重要。细胞因子转化生长因子β（TGFβ）在促进人间充质干细胞（hMSCs）的软骨分化中起着关键作用。传统的软骨诱导方法利用可溶的传递方法，这种方法在临床转化方面的应用有限。在这项工作中，我们在 TGFβ上引入了一个反应性巯基，并使用光引发的巯基-丙烯酰基聚合机制将生长因子共价键接到聚乙二醇（PEG）水凝胶中。我们使用 SMAD2 报告细胞系来证明聚合前后硫醇化 TGFβ的生物活性。hMSCs 被包封在带有和不带有固定 TGFβ的 PEG 水凝胶中，然后通过检测糖胺聚糖和胶原 II 的产生来作为软骨形成的指标进行检测。在 21 天的时间过程中，固定的 TGFβ以类似于使用可溶性生长因子的阳性对照的水平促进软骨形成。这些结果表明，固定的 TGFβ材料可以成功地用于促进 MSC 的软骨分化。
