טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentGonen-Wadmany Maya
SubjectMechanical Stimulation of Tissue Engineered Cardiac Muscle
DepartmentDepartment of Biomedical Engineering
Supervisors Professor Dror Seliktar
Professor Lior Gepstein


Abstract

The present study describes our efforts to develop a cardiac patch that can be locally implanted into a myocardial infraction. The requirements of restoring the contractile function of the diseased heart using a cardiac patch must aspire to true tissue integration with the host myocardium and synchronous contraction thereafter. In the present work, we describe the development of a 3D bioartificial cardiac muscle with defined geometry and cellular organization that enables better host-tissue integration.  We hypothesized that mechanical stimulation can be used to regulate cell-mediated functional reorganization of the tissue constructs and that this stimulation would initiate the cardiomyocytes to reorient into longitudinal configuration, causing tissue reorganization and subsequent phenotypic changes to the cells. The mechanical stimulation is imparted by a bioreactor system that is designed to mimic the natural myocardial wall motion.  We prepared engineered constructs from neonatal rat cardiac cells, smooth muscle cells and reconstituted collagen for use in the bioreactor system. After an initial period of cellular compaction, the constructs were inserted into the bioreactor and cyclically strained. We controlled the organization of cells in the tissue constructs by applying up to 12.5% cyclic radial strain at a 1-Hz frequency with a precisely controlled duty cycle. The results demonstrate that the strain stimulation guides cellular orientation in the direction of applied strain (i.e., in the circumferential direction). The cellular and morphological reorganization is highly dependent on the amplitude of the strain stimulation. The stimulated constructs exhibited a cardiac phenotype and increased protein content. In conclusion, the cellular reorganization produces defined cellular organization and structural characteristics that are similar to that of the mature native tissue.