2. ENGINEERED “SMART” MATERIALS FOR IMPROVED CARDIOMYOCYTE DIFFERENTIATION

Department: Bioengineering
Faculty Advisor(s): Adam J Engler

Primary Student
Name: Jennifer L Young
Email: jly004@ucsd.edu
Phone: 858-246-0332
Grad Year: 2013

Abstract
Recent studies have reported the importance of extracellular matrix (ECM) elasticity in directing stem cells toward a specific lineage. In particular, tissue-specific ECM elastic moduli have been shown to play an integral role in development. These findings suggest that traditional cardiomyocyte cultures on ECM-coated glass may not be the appropriate physical environment for this cell type. Rather, stem cells should be cultured in the appropriate physical conditions that mimic the progression of pre-cardiac endoderm from a soft microenvironment, E ~ 200 Pa, into a mature, less compliant cardiac tissue where E ~ 10 kPa. ECM changes also occur in diseased tissues, thereby limiting appropriate stem cell differentiation in regenerative therapies. Thus, the objective of this study is to understand the underpinnings of how and why heart muscle develops a specific elasticity, and then recreate this process in vitro by engineering a “smart” material that mimics temporal ECM changes in the myocardium. We characterized the elasticity changes in developing chicken myocardium by atomic force microscopy (AFM), and this data was used to establish the elastic parameters of collagen, fibronectin and hyaluronic (HA) matrices for the “smart” materials. Optimal time-dependent crosslinking of the gels was achieved by utilizing crosslinkers, such as poly(ethylene glycol) diacrylate (PEGDA). Stem cells were plated onto the engineered matrices, and improved cardiomyocyte differentiation was characterized by immunofluorescence after staining for proteins that mark cardiogenesis. Results from this experiment will not only have a profound impact on the field of cardiovascular engineering, but will influence the way in which many cellular regenerative therapies are conducted.

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