Abstract:
Cardiovascular disease is a major cause of death globally. This has led to significant efforts
to develop new anti‐thrombotic therapies or re‐purpose existing drugs to treat cardiovascular
diseases. Due to difficulties of obtaining healthy human blood vessel tissues to recreate in vivo
conditions, pre‐clinical testing of these drugs currently requires significant use of animal
experimentation, however, the successful translation of drugs from animal tests to use in humans
is poor. Developing humanised drug test models that better replicate the human vasculature will
help to develop anti‐thrombotic therapies more rapidly. Tissue‐engineered human blood vessel
(TEBV) models were fabricated with biomimetic matrix and cellular components. The pro‐ and anti‐
aggregatory properties of both intact and FeCl3‐injured TEBVs were assessed under physiological
flow conditions using a modified parallel‐plate flow chamber. These were perfused with
fluorescently labelled human platelets and endothelial progenitor cells (EPCs), and their responses
were monitored in real‐time using fluorescent imaging. An endothelium‐free TEBV exhibited the
capacity to trigger platelet activation and aggregation in a shear stress‐dependent manner, similar
to the responses observed in vivo. Ketamine is commonly used as an anaesthetic in current in vivo
models, but this drug significantly inhibited platelet aggregation on the injured TEBV. Atorvastatin
was also shown to enhance EPC attachment on the injured TEBV. The TEBV, when perfused with
human blood or blood components under physiological conditions, provides a powerful alternative
to current in vivo drug testing models to assess their effects on thrombus formation and EPC
recruitment
