Collagen hydrogels with controllable combined cues of elasticity and topography to regulate cellular processes

Tomoko G Oyama; Kotaro Oyama; Atsushi Kimura; Fumiya Yoshida; Ryo Ishida; Masashi Yamazaki; Hiromi Miyoshi; Mitsumasa Taguchi

doi:10.1088/1748-605X/ac0452

Collagen hydrogels with controllable combined cues of elasticity and topography to regulate cellular processes

Biomed Mater. 2021 Jun 11;16(4). doi: 10.1088/1748-605X/ac0452.

Authors

Tomoko G Oyama¹, Kotaro Oyama^{1

2}, Atsushi Kimura¹, Fumiya Yoshida^{1

3}, Ryo Ishida⁴, Masashi Yamazaki⁴, Hiromi Miyoshi⁴, Mitsumasa Taguchi¹

Affiliations

¹ Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology (QST), 1233 Watanukimachi, Takasaki-shi, Gunma 370-1292, Japan.
² PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
³ Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu-shi, Gunma 376-0052, Japan.
⁴ Graduate School of Systems Design, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo 192-0397, Japan.

PMID: 34030146
DOI: 10.1088/1748-605X/ac0452

Abstract

The elasticity, topography, and chemical composition of cell culture substrates influence cell behavior. However, the cellular responses toin vivoextracellular matrix (ECM), a hydrogel of proteins (mainly collagen) and polysaccharides, remain unknown as there is no substrate that preserves the key features of native ECM. This study introduces novel collagen hydrogels that can combine elasticity, topography, and composition and reproduce the correlation between collagen concentration (C) and elastic modulus (E) in native ECM. A simple reagent-free method based on radiation-cross-linking altered ECM-derived collagen I and hydrolyzed collagen (gelatin or collagen peptide) solutions into hydrogels with tunable elastic moduli covering a broad range of soft tissues (E= 1-236 kPa) originating from the final collagen density in the hydrogels (C= 0.3%-14%) and precise microtopographies (⩾1 μm). The amino acid composition ratio was almost unchanged by this method, and the obtained collagen hydrogels maintained enzyme-mediated degradability. These collagen hydrogels enabled investigation of the responses of cell lines (fibroblasts, epithelial cells, and myoblasts) and primary cells (rat cardiomyocytes) to soft topographic cues such as thosein vivounder the positive correlation betweenCandE. These cells adhered directly to the collagen hydrogels and chose to stay atop or spontaneously migrate into them depending onE, that is, the density of the collagen network,C. We revealed that the cell morphology and actin cytoskeleton organization conformed to the topographic cues, even when they are as soft asin vivoECM. The stiffer microgrooves on collagen hydrogels aligned cells more effectively, except HeLa cells that underwent drastic changes in cell morphology. These collagen hydrogels may not only reducein vivoandin vitrocell behavioral disparity but also facilitate artificial ECM design to control cell function and fate for applications in tissue engineering and regenerative medicine.

Keywords: collagen; elasticity; extracellular matrix; hydrogels; topography.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biocompatible Materials* / chemistry
Biocompatible Materials* / pharmacology
Cell Physiological Phenomena / drug effects*
Cells, Cultured
Collagen* / chemistry
Collagen* / pharmacology
Dogs
Elasticity / drug effects*
Extracellular Matrix / chemistry
Extracellular Matrix / drug effects
Extracellular Matrix / metabolism
HeLa Cells
Humans
Hydrogels* / chemistry
Hydrogels* / pharmacology
Madin Darby Canine Kidney Cells
Rats
Surface Properties

Substances

Biocompatible Materials
Hydrogels
Collagen