Light-Induced Cell Alignment and Harvest for Anisotropic Cell Sheet Technology
Light-Induced Cell Alignment and Harvest for Anisotropic Cell Sheet Technology
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各向异性细胞片技术的光诱导细胞排列和收获
DOI：
10.1021/acsami.7b07202
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发表时间：
2017-10-25
影响因子：
9.5
通讯作者：
Wang, Huiming
中科院分区：
文献类型：
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作者：
Liu, Chao;Zhou, Ying;Wang, Huiming
良好的细胞定向和各向异性细胞外基质(ECM)在肌肉、动脉、神经系统等仿生组织工程中是至关重要的。然而，这一战略才刚刚开始探索。在这里，我们展示了一种光诱导细胞取向和收获各向异性细胞片(ACS)技术，使用光响应性二氧化钛纳米点膜(TNF)和光交联型甲基丙烯酸明胶(Ge1MA)。细胞对肿瘤坏死因子的初始行为可能由光诱导的独特的表面羟基特征的微模式控制，这是由于肌球蛋白II驱动的片状脂蛋白收缩的传感机制。进一步的光处理使ACs从肿瘤坏死因子表面剥离，同时固化了GeIMA。实现了ACS的自动转接。此外，成功地将两个分离的AC堆积成一个单层取向可控的3D双层结构，并保持细胞排列超过7天。有趣的是，各向异性的HFF-1细胞膜通过上调VEGFA和ANGPT1，产生各向异性的ECM，进一步诱导HUVEC形成各向异性的毛细血管样网络。因此，这种开发的集成功能ACS技术提供了一种新的途径来生产具有明确定向的复杂组织结构，并可能对再生医学产生深远的影响。
Well-organized orientation of cells and anisotropic extracellular matrix (ECM) are crucial in engineering biomimetic tissues, such as muscles, arteries, and nervous system, and so on. This strategy, however, is only beginning to be explored. Here, we demonstrated a light-induced cell alignment and harvest for anisotropic cell sheets (ACS) technology using light-responsive TiO2 nanodots film (TNF) and photo-cross-linkable gelatin methacrylate (Ge1MA). Cell initial behaviors on TNF might be controlled by micropatterns of light-induced distinct surface hydroxyl features, owing to a sensing mechanism of myosin II-driven retraction of lamellipodia. Further light treatment allowed ACS detachment from TNF surface while simultaneously solidified the GeIMA,. realizing the automatic transference of ACS. Moreover, two detached ACS were successfully stacked into a 3D bilayer construct with controllable orientation of individual layer and maintained cell alignment for more than 7 days. Interestingly, the anisotropic HFF-1 cell sheets could further induce the HUVECs to form anisotropic capillary-like networks via upregulating VEGFA and ANGPT1 and producing anisotropic ECM. This developed integrated-functional ACS technology therefore provides a novel route to produce complex tissue constructs with well-defined orientations and may have a profound impact on regenerative medicine.