title: Micromolded gelatin hydrogels for extended culture of engineered cardiac tissues.
abstract: Defining the chronic cardiotoxic effects of drugs during preclinical screening is hindered by the relatively short lifetime of functional cardiac tissues in vitro, which are traditionally cultured on synthetic materials that do not recapitulate the cardiac microenvironment. Because collagen is the primary extracellular matrix protein in the heart, we hypothesized that micromolded gelatin hydrogel substrates tuned to mimic the elastic modulus of the heart would extend the lifetime of engineered cardiac tissues by better matching the native chemical and mechanical microenvironment. To measure tissue stress, we used tape casting, micromolding, and laser engraving to fabricate gelatin hydrogel muscular thin film cantilevers. Neonatal rat cardiac myocytes adhered to gelatin hydrogels and formed aligned tissues as defined by the microgrooves. Cardiac tissues could be cultured for over three weeks without declines in contractile stress. Myocytes on gelatin had higher spare respiratory capacity compared to those on fibronectin-coated PDMS, suggesting that improved metabolic function could be contributing to extended culture lifetime. Lastly, human induced pluripotent stem cell-derived cardiac myocytes adhered to micromolded gelatin surfaces and formed aligned tissues that remained functional for four weeks, highlighting their potential for human-relevant chronic studies.
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: McCain
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Haley W
authors.initials: HW
authors.lastname: Nesmith
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Nesmith
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. Electronic address: kkparker@seas.harvard.edu.
authors.forename: Kevin Kit
authors.initials: KK
authors.lastname: Parker
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D040761:Biomimetic Materials / Q000378:metabolism; D002478:Cells, Cultured; D055119:Elastic Modulus; D005353:Fibronectins / Q000378:metabolism; D005780:Gelatin / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D005353:Fibronectins; D020100:Hydrogels; C015233:gelatin film; D005780:Gelatin
keywords: Mechanotransduction; Metabolism; Organs on chips; Tissue engineering
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