Micromolded gelatin hydrogels for extended culture of engineered cardiac tissues

Megan L. McCain, Ashutosh Agarwal, Haley W. Nesmith, Alexander P. Nesmith, Kevin Kit Parker

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Defining the chronic cardiotoxic effects of drugs during preclinical screening is hindered by the relatively short lifetime of functional cardiac tissues invitro, 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.

Original languageEnglish (US)
Pages (from-to)5462-5471
Number of pages10
JournalBiomaterials
Volume35
Issue number21
DOIs
StatePublished - Jul 2014

Keywords

  • Mechanotransduction
  • Metabolism
  • Organs on chips
  • Tissue engineering

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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