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Conditioning of hiPSC-derived cardiomyocytes using surface topography obtained with high throughput technology
Biomedical Materials ( IF 4 ) Pub Date : 2021-09-09 , DOI: 10.1088/1748-605x/ac1f73
Lucas R X Cortella 1 , Idágene A Cestari 1 , Ricardo D Lahuerta 1 , Matheus C Araña 1 , Marcos Soldera 2, 3 , Andreas Rank 2 , Andrés F Lasagni 2, 4 , Ismar N Cestari 1
Affiliation  

Surface functionalization of polymers aims to introduce novel properties that favor bioactive responses. We have investigated the possibility of surface functionalization of polyethylene terephthalate (PET) sheets by the combination of laser ablation with hot embossing and the application of such techniques in the field of stem cell research. We investigated the response of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to topography in the low micrometer range. HiPSC-CMs are expected to offer new therapeutic tools for myocardial replacement or regeneration after an infarct or other causes of cardiac tissue loss. However, hiPSC-CMs are phenotypically immature compared to myocytes in the adult myocardium, hampering their clinical application. We aimed to develop and test a high-throughput technique for surface structuring that would improve hiPSC-CMs structural maturation. We used laser ablation with a ps-laser source in combination with nanoimprint lithography to fabricate large areas of homogeneous micron- to submicron line-like pattern with a spatial period of 3 m on the PET surface. We evaluated cell morphology, alignment, sarcomeric myofibrils assembly, and calcium transients to evaluate phenotypic changes associated with culturing hiPSC-CMs on functionalized PET. Surface functionalization through hot embossing was able to generate, at low cost, low micrometer features on the PET surface that influenced the hiPSC-CMs phenotype, suggesting improved structural and functional maturation. This technique may be relevant for high-throughput technologies that require conditioning of hiPSC-CMs and may be useful for the production of these cells for drug screening and disease modeling applications with lower costs.



中文翻译:

使用通过高通量技术获得的表面形貌对 hiPSC 衍生的心肌细胞进行调理

聚合物的表面功能化旨在引入有利于生物活性反应的新特性。我们研究了通过激光烧蚀与热压印相结合来实现聚对苯二甲酸乙二醇酯 (PET) 片材表面功能化的可能性,以及此类技术在干细胞研究领域的应用。我们研究了人类诱导多能干细胞衍生的心肌细胞 (hiPSC-CMs) 对低微米范围内地形的反应。HiPSC-CM 有望在梗塞或其他导致心脏组织丢失的原因后为心肌置换或再生提供新的治疗工具。然而,与成人心肌中的肌细胞相比,hiPSC-CM 在表型上不成熟,阻碍了它们的临床应用。我们的目标是开发和测试一种用于表面结构化的高通量技术,以提高 hiPSC-CM 的结构成熟度。我们使用 ps 激光源的激光烧蚀与纳米压印光刻相结合,在 PET 表面上制造大面积均匀的微米至亚微米线状图案,空间周期为 3 m。我们评估了细胞形态、排列、肌节肌原纤维组装和钙瞬变,以评估与在功能化 PET 上培养 hiPSC-CM 相关的表型变化。通过热压花的表面功能化能够以低成本在 PET 表面上产生影响 hiPSC-CM 表型的低微米特征,表明结构和功能成熟度得到改善。

更新日期:2021-09-09
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