Building 3D tissue scaffolds to repair damaged hearts

By Megan Mayerle, PhD

September 4, 2019

Over 700,000 people in the United States suffer from heart attacks each year. In order to treat these patients, scientists and clinicians have increasingly been looking to regenerative medicine and therapeutic cell delivery. However, clinical trials of therapeutic cell delivery have generally shown minimal to moderate benefit in improving the heart’s pumping capacity.

Tissue engineering has emerged as an alternative method to regenerate heart tissue and to encourage new blood vessels to form in the heart. A key component of engineered tissues is the extracellular matrix (ECM), a scaffold for cells that provides important cues to cells through properties such as spatial patterning, stiffness, and cell binding domains.

Blood vessel formation is critical to the survival of the engineered heart tissue. A group of Stanford scientists led by Cardiovascular Institute member Dr. Ngan Huang have recently published a study in Frontiers in Bioengineering and Biotechnology looking at how the three-dimensional organization of engineered tissue scaffolds impacts how well blood vessel networks form in these tissues.

The researchers designed scaffolds with different levels of organization and seeded them with cardiomyocytes and endothelial cells differentiated from induced pluripotent stem cells and then compared how well the different tissues functioned in a heart injury animal model. They found that different scaffold alignments facilitated different biological processes. For example, parallel-aligned scaffolds preferentially directed the formation of capillaries along the direction and plane of the scaffold microfibers. By contrast, endothelial cells survived better in randomly aligned scaffolds. These findings are important because they suggest that scaffold topography plays a key role in modulating cellular survival, vascularization, and microvessel architecture.

Stanford researchers Maureen Wanjare, Masashi Kawamura, Caroline Hu, Cynthia Alcazar, Hanjay Wang, Y. Joseph Woo, and Ngan F. Huang contributed to this study. This work was supported by the US Department of Veterans Affairs, the US National Institutes of Health, and the American Heart Association.

Dr. Ngan Huang