Methacrylated human recombinant collagen peptide as a hydrogel for manipulating and monitoring stiffness-related cardiac cell behavior
Dylan Mostert,
Ignasi Jorba,
Bart G.W. Groenen,
Robert Passier,
Marie-José T.H. Goumans,
Huibert A. van Boxtel,
Nicholas A. Kurniawan,
Carlijn V.C. Bouten,
Leda Klouda
Affiliations
Dylan Mostert
Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, the Netherlands; Institute for Complex Molecular Systems (ICMS), 5600 MB Eindhoven, the Netherlands
Ignasi Jorba
Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, the Netherlands; Institute for Complex Molecular Systems (ICMS), 5600 MB Eindhoven, the Netherlands
Bart G.W. Groenen
Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, the Netherlands
Robert Passier
Department of Applied Stem Cell Technologies, University of Twente, 7522 NB Enschede, the Netherlands; Department of Anatomy and Embryology, Leiden University Medical Centre, 2333 ZA Leiden, the Netherlands
Marie-José T.H. Goumans
Department of Cell and Chemical Biology and Center for Biomedical Genetics, Leiden University Medical Centre, 2333 ZA Leiden, the Netherlands
Huibert A. van Boxtel
Fujifilm Manufacturing Europe B.V., 5047 TK Tilburg, the Netherlands
Nicholas A. Kurniawan
Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, the Netherlands; Institute for Complex Molecular Systems (ICMS), 5600 MB Eindhoven, the Netherlands
Carlijn V.C. Bouten
Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, the Netherlands; Institute for Complex Molecular Systems (ICMS), 5600 MB Eindhoven, the Netherlands; Corresponding author
Leda Klouda
Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven, the Netherlands; Department of Engineering, Rangos School of Health Sciences, Duquesne University, Pittsburgh, PA 15282, USA
Summary: Environmental stiffness is a crucial determinant of cell function. There is a long-standing quest for reproducible and (human matrix) bio-mimicking biomaterials with controllable mechanical properties to unravel the relationship between stiffness and cell behavior. Here, we evaluate methacrylated human recombinant collagen peptide (RCPhC1-MA) hydrogels as a matrix to control 3D microenvironmental stiffness and monitor cardiac cell response. We show that RCPhC1-MA can form hydrogels with reproducible stiffness in the range of human developmental and adult myocardium. Cardiomyocytes (hPSC-CMs) and cardiac fibroblasts (cFBs) remain viable for up to 14 days inside RCPhC1-MA hydrogels while the effect of hydrogel stiffness on extracellular matrix production and hPSC-CM contractility can be monitored in real-time. Interestingly, whereas the beating behavior of the hPSC-CM monocultures is affected by environmental stiffness, this effect ceases when cFBs are present. Together, we demonstrate RCPhC1-MA to be a promising candidate to mimic and control the 3D biomechanical environment of cardiac cells.
