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 (Corresponding author), Leda Klouda

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Abstract

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.

Original languageEnglish
Article number106423
JournaliScience
Volume26
Issue number4
DOIs
Publication statusPublished - 21 Apr 2023

Bibliographical note

Funding Information:
This research was financially supported by the Gravitation Program “Materials Driven Regeneration,” funded by the Netherlands Organization for Scientific Research ( 024.003.013 ). N. A. Kurniawan and C.V.C. Bouten acknowledge financial support from the European Research Council (NAK: 851960 ; CVCB: 101054726 ). I. Jorba acknowledges financial support from the Dutch Research Council ( OCENW.XS21.4.146 ). M. Vissers (Multiscale lab, Eindhoven University of Technology) is gratefully acknowledged for his help in performing the SEM imaging. Milan van Wezel from the Institute for Complex Molecular Systems Animation Studio is kindly acknowledged for his help in creating the graphical abstract.

Funding Information:
This research was financially supported by the Gravitation Program “Materials Driven Regeneration,” funded by the Netherlands Organization for Scientific Research (024.003.013). N. A. Kurniawan and C.V.C. Bouten acknowledge financial support from the European Research Council (NAK: 851960; CVCB: 101054726). I. Jorba acknowledges financial support from the Dutch Research Council (OCENW.XS21.4.146). M. Vissers (Multiscale lab, Eindhoven University of Technology) is gratefully acknowledged for his help in performing the SEM imaging. Milan van Wezel from the Institute for Complex Molecular Systems Animation Studio is kindly acknowledged for his help in creating the graphical abstract. Conceptualization, D.M. I.J. and L.K.; methodology and investigation, D.M. I.J. H.B. and B.G.; writing – original draft, D.M. and I.J.; writing – review and editing, D.M. I.J. L.K. N.A.K. and C.V.C.B.; funding acquisition, I.J. N.A.K. and C.V.C.B.; resources, R.P. H.B. and M.G; supervision, N.A.K. and C.V.C.B. H.A. van Boxtel is an employee of Fujifilm Manufacturing Europe B.V. The results of this study were not influenced by him or any other employee of Fujifilm Manufacturing Europe B.V.

Keywords

  • Biomaterials
  • Cell biology
  • Materials in biotechnology
  • Stem cells research

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