Universität zu Köln

Ozturk-Oncel, M. Ozgen, Heras-Bautista, Carlos O., Uzun, Lokman ORCID: 0000-0002-3971-7725, Hur, Deniz, Hescheler, Juergen, Pfannkuche, Kurt and Garipcan, Bora (2021). 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. ACS Biomater. Sci. Eng., 7 (4). S. 1539 - 1552. WASHINGTON: AMER CHEMICAL SOC. ISSN 2373-9878

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ozturk-Oncel, M. Ozgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Heras-Bautista, Carlos O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Uzun, Lokman UNSPECIFIED orcid.org/0000-0002-3971-7725 UNSPECIFIED Hur, Deniz UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfannkuche, Kurt UNSPECIFIED UNSPECIFIED UNSPECIFIED Garipcan, Bora UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-586096
DOI:	10.1021/acsbiomaterials.0c01434
Journal or Publication Title:	ACS Biomater. Sci. Eng.
Volume:	7
Number:	4
Page Range:	S. 1539 - 1552
Date:	2021
Publisher:	AMER CHEMICAL SOC
Place of Publication:	WASHINGTON
ISSN:	2373-9878
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HYDROPHOBIC RECOVERY; COVALENT ATTACHMENT; FUNCTIONAL-GROUPS; ADHESION; MATRIX; HEART; TISSUE; PDMS; PROLIFERATION; ARCHITECTURE Multiple languages Materials Science, Biomaterials Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58609