Hierarchical Topography with Tunable Micro‐ and Nanoarchitectonics for Highly Enhanced Cardiomyocyte Maturation via Multi‐Scale Mechanotransduction

Author:

Ahn Hyunah1ORCID,Cho Younghak23,Yun Geun‐Tae4,Jung Kwang Bo5,Jeong Wonji23,Kim Yesol23,Son Mi‐Young5,Lee Eunjung23,Im Sung Gap23,Jung Hee‐Tae1ORCID

Affiliation:

1. National Laboratory for Organic Opto‐Electronic Material Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology (KAIST) 291 Daehak‐ro, Yuseong‐gu Daejeon 34141 Korea

2. Functional Thin Film Laboratory Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology (KAIST) 291 Daehak‐ro, Yuseong‐gu Daejeon 34141 Korea

3. KI for NanoCentury KAIST, 291 Daehak‐ro, Yuseong‐gu Daejeon 34141 Korea

4. National Nanofab Center Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Korea

5. Korea Research Institute of Bioscience and Biotechnology (KRIBB) Daejeon 34141 Korea

Abstract

AbstractEnhancing cardiomyocyte (CM) maturation by topographical cues is a critical issue in cardiac tissue engineering. Thus far, single‐scale topographies with a broad range of feature shapes and dimensions have been utilized including grooves, pillars, and fibers. This study reports for the first time a hierarchical structure composed of nano‐pillars (nPs) on micro‐wrinkles (µWs) for effective maturation of CMs. Through capillary force lithography followed by a wrinkling process, vast size ranges of topographies are fabricated, and the responses of CMs are systematically investigated. Maturation of CMs on the hierarchical structures is highly enhanced compared to a single‐scale topography: cardiac differentiation of H9C2s (rat cardiomyocytes) on the hierarchical topography is ≈ 2.8 and ≈ 1.9 times higher than those consisting of single‐scale µWs and nPs. Both nPs and µWs have important roles in cardiac maturation, and the aspect ratio (height/diameter) of the nPs and the wavelength of the µWs are important in CM maturation. This enhancement is caused by strong focal adhesion and nucleus mediated mechanotransduction of CMs from the confinement effects of the different wavelengths of µWs and the cellular membrane protrusion on the nPs. This study demonstrates how a large family of hierarchical structures is used for cardiac maturation.

Funder

Electronics and Telecommunications Research Institute

Ministry of Trade, Industry and Energy

National Research Foundation of Korea

Publisher

Wiley

Subject

Pharmaceutical Science,Biomedical Engineering,Biomaterials

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