Engineered Contractile Skeletal Muscle Tissue on a Microgrooved Methacrylated Gelatin Substrate
Engineered Contractile Skeletal Muscle Tissue on a Microgrooved Methacrylated Gelatin Substrate
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DOI：
10.1089/ten.tea.2012.0181
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发表时间：
2012-12-01
影响因子：
4.1
通讯作者：
Khademhosseini, Ali
中科院分区：
文献类型：
--
作者：
Hosseini, Vahid;Ahadian, Samad;Khademhosseini, Ali
为了设计类组织结构，细胞必须将自己组织成三维（3D）网络，以模仿天然组织的微结构。微制备水凝胶底物为在体外引导细胞进入仿生组织结构提供了一个潜在的有用平台。在这里，我们提出微槽甲基丙烯酸明胶水凝胶作为一个合适的平台，以一种简单和高度可复制的方式构建肌肉样纤维结构。制备了两种不同脊大小（50 μ m和100 μ m）的微沟槽水凝胶基质，以评估工程肌纤维之间的距离对桥接C2C12成肌细胞方向和由此产生的多核肌管形成的影响。结果表明，尽管脊大小对C2C12成肌细胞排列没有显著影响，但与脊小的微图案水凝胶相比，脊宽的微图案水凝胶产生了更多不向槽方向排列的肌管。我们也证明了电刺激改善了成肌细胞的排列，并增加了肌管的直径。通过使用微结构甲基丙烯酸明胶基质，我们建立了独立的3D肌肉片，当电刺激时收缩。由于其强大的收缩性和仿生微结构，工程组织可能在组织工程、生物学研究、高通量药物筛选和生物机器人中得到应用。
To engineer tissue-like structures, cells must organize themselves into three-dimensional (3D) networks that mimic the native tissue microarchitecture. Microfabricated hydrogel substrates provide a potentially useful platform for directing cells into biomimetic tissue architecture in vitro. Here, we present microgrooved methacrylated gelatin hydrogels as a suitable platform to build muscle-like fibrous structures in a facile and highly reproducible fashion. Microgrooved hydrogel substrates with two different ridge sizes (50 and 100 [mu m) were fabricated to assess the effect of the distance between engineered myofibers on the orientation of the bridging C2C12 myoblasts and the formation of the resulting multinucleated myotubes. It was shown that although the ridge size did not significantly affect the C2C12 myoblast alignment, the wider-ridged micropatterned hydrogels generated more myotubes that were not aligned to the groove direction as compared to those on the smaller-ridge micropatterns. We also demonstrated that electrical stimulation improved the myoblast alignment and increased the diameter of the resulting myotubes. By using the microstructured methacrylated gelatin substrates, we built free-standing 3D muscle sheets, which contracted when electrically stimulated. Given their robust contractility and biomimetic microarchitecture, engineered tissues may find use in tissue engineering, biological studies, high-throughput drug screening, and biorobotics.