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Multifunctional Thermoresponsive Microcarriers for High-Throughput Cell Culture and Enzyme-Free Cell Harvesting
Small ( IF 13.0 ) Pub Date : 2021-09-23 , DOI: 10.1002/smll.202103192 Seyed Mohammad Hossein Dabiri 1, 2 , Ehsan Samiei 1, 2 , Shahla Shojaei 1, 2 , Lucas Karperien 1, 2 , Bardia Khun Jush 1 , Tavia Walsh 1, 2 , Maryam Jahanshahi 1, 2 , Sadegh Hassanpour 1, 2 , David Hamdi 1, 2 , Amir Seyfoori 1, 2 , Samad Ahadian 3 , Ali Khademhosseini 3 , Mohsen Akbari 1, 2, 4
Small ( IF 13.0 ) Pub Date : 2021-09-23 , DOI: 10.1002/smll.202103192 Seyed Mohammad Hossein Dabiri 1, 2 , Ehsan Samiei 1, 2 , Shahla Shojaei 1, 2 , Lucas Karperien 1, 2 , Bardia Khun Jush 1 , Tavia Walsh 1, 2 , Maryam Jahanshahi 1, 2 , Sadegh Hassanpour 1, 2 , David Hamdi 1, 2 , Amir Seyfoori 1, 2 , Samad Ahadian 3 , Ali Khademhosseini 3 , Mohsen Akbari 1, 2, 4
Affiliation
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An effective treatment of human diseases using regenerative medicine and cell therapy approaches requires a large number of cells. Cultivation of cells on microcarriers is a promising approach due to the high surface-to-volume ratios that these microcarriers offer. Here, multifunctional temperature-responsive microcarriers (cytoGel) made of an interpenetrating hydrogel network composed of poly(N-isopropylacrylamide) (PNIPAM), poly(ethylene glycol) diacrylate (PEGDA), and gelatin methacryloyl (GelMA) are developed. A flow-focusing microfluidic chip is used to produce microcarriers with diameters in the range of 100–300 μm and uniform size distribution (polydispersity index of ≈0.08). The mechanical properties and cells adhesion properties of cytoGel are adjusted by changing the composition hydrogel composition. Notably, GelMA regulates the temperature response and enhances microcarrier stiffness. Human-derived glioma cells (U87) are grown on cytoGel in static and dynamic culture conditions with cell viabilities greater than 90%. Enzyme-free cell detachment is achieved at room temperature with up to 70% detachment efficiency. Controlled release of bioactive molecules from cytoGel is accomplished for over a week to showcase the potential use of microcarriers for localized delivery of growth factors to cell surfaces. These microcarriers hold great promise for the efficient expansion of cells for the industrial-scale culture of therapeutic cells.
中文翻译：
用于高通量细胞培养和无酶细胞收获的多功能热响应微载体
使用再生医学和细胞疗法有效治疗人类疾病需要大量细胞。由于这些微载体提供的高表面积与体积比，在微载体上培养细胞是一种很有前景的方法。在这里，多功能温度响应微载体（cytoGel）由相互渗透的水凝胶网络制成，由聚（N-异丙基丙烯酰胺）（PNIPAM）、聚（乙二醇）二丙烯酸酯（PEGDA）和明胶甲基丙烯酰（GelMA）。流动聚焦微流控芯片用于生产直径在 100-300 μm 范围内且尺寸分布均匀（多分散指数≈0.08）的微载体。cytoGel 的机械性能和细胞粘附性能是通过改变水凝胶组成来调整的。值得注意的是，GelMA 调节温度响应并增强微载体刚度。人源性神经胶质瘤细胞 (U87) 在 cytoGel 上在静态和动态培养条件下生长，细胞活力大于 90%。在室温下实现无酶细胞分离，分离效率高达 70%。从 cytoGel 中受控释放生物活性分子需要一个多星期，以展示微载体在将生长因子局部递送至细胞表面的潜在用途。这些微载体在有效扩增细胞以用于治疗细胞的工业规模培养方面具有广阔的前景。
更新日期：2021-11-04
中文翻译：
用于高通量细胞培养和无酶细胞收获的多功能热响应微载体
使用再生医学和细胞疗法有效治疗人类疾病需要大量细胞。由于这些微载体提供的高表面积与体积比，在微载体上培养细胞是一种很有前景的方法。在这里，多功能温度响应微载体（cytoGel）由相互渗透的水凝胶网络制成，由聚（N-异丙基丙烯酰胺）（PNIPAM）、聚（乙二醇）二丙烯酸酯（PEGDA）和明胶甲基丙烯酰（GelMA）。流动聚焦微流控芯片用于生产直径在 100-300 μm 范围内且尺寸分布均匀（多分散指数≈0.08）的微载体。cytoGel 的机械性能和细胞粘附性能是通过改变水凝胶组成来调整的。值得注意的是，GelMA 调节温度响应并增强微载体刚度。人源性神经胶质瘤细胞 (U87) 在 cytoGel 上在静态和动态培养条件下生长，细胞活力大于 90%。在室温下实现无酶细胞分离，分离效率高达 70%。从 cytoGel 中受控释放生物活性分子需要一个多星期，以展示微载体在将生长因子局部递送至细胞表面的潜在用途。这些微载体在有效扩增细胞以用于治疗细胞的工业规模培养方面具有广阔的前景。
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