Micromolded gelatin hydrogels for extended culture of engineered cardiac tissues.
Micromolded gelatin hydrogels for extended culture of engineered cardiac tissues.
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DOI：
10.1016/j.biomaterials.2014.03.052
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发表时间：
2014-07
期刊：
影响因子：
14
通讯作者：
Parker, Kevin Kit
中科院分区：
文献类型：
--
作者：
McCain, Megan L.;Agarwal, Ashutosh;Nesmith, Haley W.;Nesmith, Alexander P.;Parker, Kevin Kit
在临床前筛选过程中定义药物的慢性心脏毒性作用受到体外功能性心脏组织相对较短寿命的阻碍，这些组织传统上是在不能重现心脏微环境的合成材料上培养的。由于胶原蛋白是心脏中主要的细胞外基质蛋白，我们假设微模制明胶水凝胶基质经过调整以模拟心脏的弹性模量，可以通过更好地匹配天然化学和机械微环境来延长工程心脏组织的寿命。为了测量组织应力，我们使用流延成型、微成型和激光雕刻来制造明胶水凝胶肌肉薄膜悬臂梁。新生大鼠心肌细胞粘附在明胶水凝胶上并形成微纹所定义的排列组织。心脏组织可以培养三周以上，收缩应力不会下降。与纤连蛋白包被的 PDMS 上的肌细胞相比，明胶上的肌细胞具有更高的备用呼吸能力，这表明代谢功能的改善可能有助于延长培养寿命。最后，人类诱导多能干细胞衍生的心肌细胞粘附到微模制明胶表面并形成对齐的组织，该组织在四个星期内保持功能，突出了它们在人类相关慢性研究中的潜力。
Defining the chronic cardiotoxic effects of drugs during preclinical screening is hindered by the relatively short lifetime of functional cardiac tissues in vitro, which are traditionally cultured on synthetic materials that do not recapitulate the cardiac microenvironment. Because collagen is the primary extracellular matrix protein in the heart, we hypothesized that micromolded gelatin hydrogel substrates tuned to mimic the elastic modulus of the heart would extend the lifetime of engineered cardiac tissues by better matching the native chemical and mechanical microenvironment. To measure tissue stress, we used tape casting, micromolding, and laser engraving to fabricate gelatin hydrogel muscular thin film cantilevers. Neonatal rat cardiac myocytes adhered to gelatin hydrogels and formed aligned tissues as defined by the microgrooves. Cardiac tissues could be cultured for over three weeks without declines in contractile stress. Myocytes on gelatin had higher spare respiratory capacity compared to those on fibronectin-coated PDMS, suggesting that improved metabolic function could be contributing to extended culture lifetime. Lastly, human induced pluripotent stem cell-derived cardiac myocytes adhered to micromolded gelatin surfaces and formed aligned tissues that remained functional for four weeks, highlighting their potential for human-relevant chronic studies.
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影响因子：
19
作者：
Agarwal A;Farouz Y;Nesmith AP;Deravi LF;McCain ML;Parker KK
通讯作者：
Parker KK
影响因子：
14
作者：
Feinberg, Adam W.;Alford, Patrick W.;Jin, Hongwei;Ripplinger, Crystal M.;Werdich, Andreas A.;Sheehy, Sean P.;Grosberg, Anna;Parker, Kevin Kit
通讯作者：
Parker, Kevin Kit
影响因子：
6.1
作者：
Grosberg A;Alford PW;McCain ML;Parker KK
通讯作者：
Parker KK
影响因子：
14
作者：
Hopp, Isabel;Michelmore, Andrew;Vasilev, Krasimir
通讯作者：
Vasilev, Krasimir
影响因子：
14
作者：
Alford, Patrick W.;Feinberg, Adam W.;Sheehy, Sean P.;Parker, Kevin K.
通讯作者：
Parker, Kevin K.