Cardiac Patch Research

Cardiovascular

Tissue Engineering

In this line of research, we aim at creating 3D functional cardiac tissue constructs using a variety of bioengineering approaches including 3D bioprinting, perfusion bioreactors, induced pluripotent stem cell (iPSC) technology, and Faraday waves. The bioartificial cardiac scaffolds are used either as cardiac patch to repair/regenerate damaged heart tissue in vivo, or as in vitro tissue culture platforms to model a variety of (pediatric) diseases and/or conduct drug screening.

A. Bioengineered Cardiac Patch

Cardiac patch system consists of a biomaterial with physiomechanical properties mimicking those of the embryonic heart tissue. The patch, loaded with an epicardial paracrine peptide, follistatin-like 1 (FSTL1), has shown an unprecedented pro-proliferative and regenerative effect on ischemic myocardium (i.e. heart attack).

Current directions of project:

Completing the pre-clinical pig study (cardiac patch – myocardial infarction model) and preparation for human clinical trials.
Using 3D bioprinting to incorporate vasculature into our cardiac path system.
Study the regenerative impact of incorporation of cardiac progenitor cells into the patch.

Selected publications related to this project

K. Wei+, V. Serpooshan+ (Co-First Author), ..., M.J. Butte, P.C. Yang, K. Walsh, B. Zhou, D. Bernstein, M. Mercola, and P. Ruiz-Lozano. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature 525, 479-85, 2015.

M. Mahmoudi, M. Yu, V. Serpooshan, J.C. Wu, R. Langer, R.T. Lee, J.M. Karp, and O.C. Farokhzad, Multiscale technologies for treatment of ischemic cardiomyopathy. Nature Nanotechnology 12, 845-855, 2017.

V. Serpooshan, Y.H. Liu, J.W. Buikema, F.X. Galdos, O. Chirikian, S. Paige,..., D.A. Pijnappels, and Sean M. Wu. Nkx2.5+ cardiomyoblasts contribute to cardiomyogenesis in the neonatal heart. Scientific Reports 7, 12590, 2017.

V. Serpooshan, P. Chen, ..., M. Yarmush, F. Yang, J.C. Wu, U. Demirci, and S.M. Wu. Bioacoustic-enabled patterning of human iPSC-derived cardiomyocytes into 3D cardiac tissue. Biomaterials 131, 47-57, 2017.

S. Lee, V. Serpooshan, ..., J.C. Wu, S.M. Wu, and F. Yang. Contractile force generation by 3D hiPSC-derived cardiac tissues is enhanced by rapid establishment of cellular interconnection in matrix with muscle-mimicking stiffness. Biomaterials 131, 111-120, 2017.

V. Serpooshan, M. Mahmoudi, D.A. Hu, J.B. Hu, and S.M. Wu. Bioengineering cardiac constructs using 3D printing. Journal of 3D Printing in Medicine, DOI: 10.2217/3dp-2016-0009.

S.A. Doppler, M.A. Deutsch, V. Serpooshan, G. Li, E. Dzilic, R. Lange, M. Krane, and S.M. Wu. Mammalian Heart Regeneration: The Race to the Finish Line. Circulation Research 120, 630-632, 2017.

B. Pediatric Cardiovascular Disease Modeling

B.1 Hypoplastic Left Heart Syndrome (HLHS)

By employing 3D bioprinting, perfusion bioreactor, and human iPSC technologies, we are working on development of disease-specific, 3D vascular platforms to model a variety of pediatric disease including the HLHS.

Human iPSCs are obtained from healthy and HLHS donors, differentiated into cardiac cells (cardiomyocytes and endothelial cells), and seeded in 2D and 3D cultures. A 3D bioprinter is used to create 3D vascular tissue constructs that can be perfused using a bioreactor. By applying different flow rates/regimens, we recapitulate the impaired flow conditions in the developing heart in HLHS children and study how flow-induced mechanosensation may result in abnormal cardiac tissue growth and function.