Impact of Poly(dimethylsiloxane) Surface Modification with Conventional and Amino Acid-Conjugated Self-Assembled Monolayers on the Differentiation of Induced Pluripotent Stem Cells into Cardiomyocytes
| Autor: | Deniz Hür, Kurt Pfannkuche, Carlos O Heras-Bautista, Jürgen Hescheler, Bora Garipcan, M. Özgen Öztürk-Öncel, Lokman Uzun |
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| Rok vydání: | 2021 |
| Předmět: |
Induced Pluripotent Stem Cells
0206 medical engineering Cell Biomedical Engineering Octadecyltrimethoxysilane 02 engineering and technology Biomaterials Extracellular matrix chemistry.chemical_compound medicine Humans Myocytes Cardiac Dimethylpolysiloxanes Amino Acids Induced pluripotent stem cell chemistry.chemical_classification Cell Differentiation Self-assembled monolayer Adhesion 021001 nanoscience & nanotechnology 020601 biomedical engineering Amino acid medicine.anatomical_structure chemistry Biophysics Surface modification 0210 nano-technology |
| Zdroj: | ACS Biomaterials Science & Engineering. 7:1539-1551 |
| ISSN: | 2373-9878 |
| DOI: | 10.1021/acsbiomaterials.0c01434 |
| Popis: | Cardiomyocytes, differentiated from induced pluripotent stem cells (iPSCs), have the potential to produce patient- and disease-specific pharmacological and toxicological platforms, in addition to their cardiac cell therapy applications. However, the lack of both a robust and a simple procedure for scalable cell substrate production is one of the major limitations in this area. Mimicking the natural healthy myocardium extracellular matrix (ECM) properties by altering the cell substrate properties, such as stiffness and chemical/biochemical composition, can significantly affect cell substrate interfacial characteristics and potentially influence cellular behavior and differentiation of iPSCs to cardiomyocytes. Here, we propose a systematic and biomimetic approach, based on the preparation of poly(dimethylsiloxane) (PDMS) substrates having the similar stiffness as healthy heart tissue and a well-defined surface chemistry obtained by conventional [(3-aminopropyl)triethoxysilane (APTES) and octadecyltrimethoxysilane (OTS)] and amino acid (histidine and leucine)-conjugated self-assembled monolayers (SAMs). Among a wide range of different concentrations, the 50:1 prepolymer cross-linker ratio of PDMS allowed adaptation of the myocardium stiffness with a Young's modulus of 23.79 +/- 0.61 kPa. Compared with conventional SAM modification, amino acidconjugated SAMs greatly improved iPSC adhesion, viability, and cardiac marker expression by increasing surface biomimetic properties, whereas all SAMs enhanced cell behavior, with respect to native PDMS. Furthermore, leucine-conjugated SAM modification provided the best environment for cardiac differentiation of iPSCs. This optimized approach can be easily adapted for cardiac differentiation of iPSCs in vitro, rendering a very promising tool for microfluidics, drug screening, and organ-on-chip platforms. |
| Databáze: | OpenAIRE |
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