A modular approach to cardiac tissue engineering.
Functional cardiac tissue was prepared using a modular tissue engineering approach with the goal of creating vascularized tissue. Rat aortic endothelial cells (RAEC) were seeded onto submillimeter-sized modules made of type I bovine collagen supplemented with Matrigel™ (25% v/v) embedded with cardiomyocyte (CM)-enriched neonatal rat heart cells and assembled into a contractile, macroporous, sheet-like construct. Modules (without RAEC) cultured in 10% bovine serum (BS) were more contractile and responsive to external stimulus (lower excitation threshold, higher maximum capture rate, and greater en face fractional area changes) than modules cultured in 10% fetal BS. Incorporating 25% Matrigel in the matrix reduced the excitation threshold and increased the fractional area change relative to collagen only modules (without RAEC). A coculture medium, containing 10% BS, low Mg2+ (0.814mM), and normal glucose (5.5mM), was used to maintain RAEC junction morphology (VE-cadherin) and CM contractility, although the responsiveness of CM was attenuated with RAEC on the modules. Macroporous, sheet-like module constructs were assembled by partially immobilizing a layer of modules in alginate gel until day 8, with or without RAEC. RAEC/CM module sheets were electrically responsive; however, like modules with RAEC this responsiveness was attenuated relative to CM-only sheets. Muscle bundles coexpressing cardiac troponin I and connexin-43 were evident near the perimeter of modules and at intermodule junctions. These results suggest the potential of the modular approach as a platform for building vascularized cardiac tissue.
Leung
Brendan M
BM
Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.
Sefton
Michael V
MV
D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000166:cytology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D023822:Tissue Engineering / Q000379:methods*