Photocrosslinking of gelatin macromers to synthesize porous hydrogels that promote valvular interstitial cell function.
Photocrosslinking of gelatin macromers to synthesize porous hydrogels that promote valvular interstitial cell function.
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DOI：
10.1089/ten.tea.2008.0545
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发表时间：
2009-11
影响因子：
--
通讯作者：
Anseth KS
中科院分区：
文献类型：
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作者：
Benton JA;DeForest CA;Vivekanandan V;Anseth KS
用于培养主动脉瓣间质细胞（VIC）的新型三维细胞培养平台的开发充满了许多挑战。尽管最可调的纯合成系统在促进细胞存活性或功能方面并不成功。另一方面，完全天然的材料缺乏机械完整性。在这里，我们探索了一种新的混合系统，由明胶大分子单体合成改性甲基丙烯酸酯功能，允许光封装的细胞。扫描电子显微镜观察显示在水凝胶内聚合期间诱导的微孔结构。这种多孔结构是可调的聚合速率，并没有出现互连孔。用胶原酶处理引起体积侵蚀，表明酶降解控制基质重塑。VICs是心脏瓣膜组织工程的重要细胞系，光包裹VICs并检测其细胞定向迁移和分化。VIC能够在培养2周内达到其天然形态。添加促纤维化生长因子转化生长因子β1加速了这一过程，并能够诱导α-平滑肌肌动蛋白和胶原蛋白-1表达增强，表明从静止成纤维细胞分化为活性肌成纤维细胞，如定量实时聚合酶链反应和免疫组织化学所示。虽然这些研究仅限于VIC，但这种新型水凝胶系统也可用于研究其他成纤维细胞类型。
The development of novel three-dimensional cell culture platforms for the culture of aortic valvular interstitial cells (VICs) has been fraught with many challenges. Although the most tunable, purely synthetic systems have not been successful at promoting cell survivability or function. On the other hand, entirely natural materials lack mechanical integrity. Here we explore a novel hybrid system consisting of gelatin macromers synthetically modified with methacrylate functionalities allowing for photoencapsulation of cells. Scanning electron microscopy observations show a microporous structure induced during polymerization within the hydrogel. This porous structure was tunable with polymerization rate and did not appear to have interconnected pores. Treatment with collagenase caused bulk erosion indicating enzymatic degradation controls the matrix remodeling. VICs, an important cell line for heart valve tissue engineering, were photoencapsulated and examined for cell-directed migration and differentiation. VICs were able to achieve their native morphology within 2 weeks of culture. The addition of the pro-fibrotic growth factor, transforming growth factor-β1, accelerated this process and also was capable of inducing enhanced α-smooth muscle actin and collagen-1 expression, indicating a differentiation from quiescent fibroblasts to active myofibroblasts as demonstrated by quantitative real-time polymerase chain reaction and immunohistochemistry. Although these studies were limited to VICs, this novel hydrogel system may also be useful for studying other fibroblastic cell types.