Abstract 12372: In-Situ Constructive Myocardial Regeneration With A 3-D Tissue-Engineered Cardiac Patch Combined Myocardial Cells and Extracellular Matrix

Objective: We developed a tissue-engineered cardiac patch derived from a myocardial cell block reinforced with extracellular matrix (ECM) to enhance in-situ myocardial regeneration. We sought to assess constructive and functional regeneration of the patch in a porcine preparation. Methods: A scaffold-free myocardial cell block was created with cardiomyocytes and embryonic fibroblast cells using a 3D Net Mold system( Fig.A ). The myocardial cell block incorporated with ECM sheets(cbECM) was surgically implanted into a right ventricular (RV) of a healthy porcine model (n=4), or Dacron patches (n=4) which served as control ( Fig.B,C ). After 60 days, the implanted patches were assessed with cardiac magnetic resonance imaging including the rest perfusion(RP) analysis, Extracellular volume fraction(ECV) analysis, and electroanatomical mapping(EAM) studies as well as post euthanasia analyses including histological analysis and Quantitative reverse transcription-polymerase chain reaction(RT-PCR). Results: RP analysis showed improved regional tissue perfusion in the cbECM patch area( Fig.D ). ECV values were much less in the cbECM patch compared to Dacron patch(36.1±3.6 vs. 72.0±13.6, p=0.012)( Fig.E ), which implied the cbECM patch had less fibrosis and edema. EAM revealed regenerated electrical conductivity in the patch as evidenced by relatively preserved voltage regions (1.11±0.8 mV) compared with the normal RV control 4.7±2.8 mV( Fig.F ). RT-PCR showed increased expression of growth factors in cbECM group( Fig.G ). Repopulation of site-specific host cells including premature cardiomyocyte and active vasculogenesis were confirmed with histology/tissue analysis( Fig.H ). Conclusions: The tissue-engineered cardiac patch facilitated in-situ constructive functional myocardial regeneration with increased regional tissue perfusion, and positive electrical activity in the porcine RV model.