Evaluation of tissue-engineered blood vessels as three-dimensional in vitro testing system in cardiovascular research

BackgroundDisturbed crosstalk between endothelial cells (ECs) and vascular smooth muscle cells (SMCs) has an important role in intimal hyperplasia and restenosis after vascular interventions, however, the exact pathomechanisms are incompletely understood. Current preclinical models inadequately recapitulate the complexity of human arteries.ObjectiveWe present tissue-engineered blood vessels (TEBVs) as a novel in vitro model and validate it for intimal hyperplasia.MethodsTEBVs fabricated from SMC suspended in fibrin gel, supported by a textile mesh, were seeded with ECs at various concentrations and subjected to arterial flow conditions in a bioreactor for 21 days. In addition, TEBVs underwent plain old balloon angioplasty (POBA) and implantation of bare metal stents (BMS) and drug-eluting stents (DES) at day 7 after fabrication. TEBVs were monitored by optical coherence tomography.ResultsTEBVs with absent or incomplete endothelial layer exhibited thicker vessel walls, more disorganized collagen. Quantitative analysis of Ki67 and αSMA revealed no statistically significant differences in SMC proliferation or contractile phenotype across varying degrees of endothelial coverage. POBA and stent implantation were feasible at day 7. 14 days post-intervention, POBA-treated TEBVs exhibited significantly thicker vessel walls than untreated controls and stented TEBVs, whereas stented TEBVs showed greater lumen diameters than unstented TEBVs. Endothelial coverage was higher in BMS than DES. Levels of IL-6, IL-8, and MCP-1 were highest in medium from BMS-treated TEBVs.ConclusionTEBVs provide a promising in vitro platform to study intimal hyperplasia. Their dimensions and wall thickness resemble human coronary arteries, making them suitable for testing new stent designs.