In Situ Myocardial Regeneration With Tissue Engineered Cardiac Patch Using Spheroid-Based 3-Dimensional Tissue

Ann Thorac Surg Short Rep. 2024 Mar;2(1):150-155. doi: 10.1016/j.atssr.2023.11.014. Epub 2023 Nov 30.

Abstract

Background: We have developed a tissue engineered cardiac patch derived from a 3-dimensional (3D) myocardial tissue reinforced with extracellular matrix in an effort to enhance in situ myocardial regeneration. The feasibility of the patch was evaluated in a porcine model by various modalities to assess both the constructive and functional aspects of regeneration.

Methods: A spheroid-based 3D multicellular tissue was created using a 3D net mold system that incorporated cardiomyocytes and embryonic fibroblast cells. The 3D multicellular tissue was incorporated with extracellular matrix sheets and surgically implanted into the right ventricle of a healthy porcine model (n = 4). After 60 days, the implanted patches were evaluated by cardiac magnetic resonance imaging and electroanatomic mapping studies as well as by post-euthanasia analyses, including measurements of mechanical viscoelasticity.

Results: Cardiac magnetic resonance imaging revealed improved regional tissue perfusion in the patch area. Electroanatomic mapping exhibited regenerated electrical conductivity in the patch, as evidenced by relatively preserved voltage regions (1.11 ± 0.8 mV) in comparison to the normal right ventricle (4.7 ± 2.8 mV). Histologic and tissue analyses confirmed repopulation of site-specific host cells, including premature cardiomyocytes and active vasculogenesis. These findings were supported by quantitative reverse transcription-polymerase chain reaction.

Conclusions: The tissue engineered cardiac patch effectively facilitated in situ constructive and functional myocardial regeneration, characterized by increased regional tissue perfusion and positive electrical activity in the porcine model.