Statement of Purpose: Cardiomyocytes derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells appear to be a promising cell source for practical applications like cell transplantation for myocardial repair, cardiotoxicity testing during drug development, and patient-specific disease modeling
. However, these cells exhibit a fetal phenotype and are functionally immature compared to cardiomyocytes in adult hearts. Maturation of stem cell derived cardiomyocyte can be promoted in a microenvironment that mimics physiologically relevant, dynamic extracellular matrix (ECM) changes in cardiac tissues
. Myocardial ECM stiffness increases during cardiac development
. Biomaterial platforms can be dynamically modulated to mimic this mechanical ECM change
. Importantly, gelatin is derived from collagen and does not require any additional extracellular matrix linkage steps to facilitate cell adhesion, and its stiffness can be tuned within physiological ranges
. The aim of this study is to develop a biomimetic two-dimensional gelatin-based hydrogel system, which stiffens temporally, for the maturation of hESC-derived cardiomyocytes. Engineering mature cardiac tissue from stem cell-derived cardiomyocytes would allow future development of improved drug testing platforms, disease models, and regenerative medicine therapies.