Animal models of cardiovascular disease as test beds of bioengineered vascular grafts

Abstract

The last two decades have seen many advances in regenerative medicine, including the development of tissue engineered vessels (TEVs) for replacement of damaged or diseased arteries or veins. Biomaterials from natural sources, as well as synthetic polymeric materials have been employed in engineering vascular grafts. Recently, cell-free grafts have become available, opening new possibilities for the next generation, off-the-shelf products. These TEVs are first tested in small or large animal models, which are usually young and healthy. However, the majority of patients in need of vascular grafts are elderly and suffer from comorbidities that may complicate their response to the implants. Therefore, it is important to evaluate TEVs in animal models of vascular disease in order to increase their predictive value and learn how the disease microenvironment may affect the patency and remodeling of vascular grafts. Small animals with various disease phenotypes are readily utilizable due to the availability of transgenic or gene knockout technologies and can be used to address mechanistic questions related to vascular grafting. On the other hand, large animal models with similar anatomy, hematology and thrombotic responses to humans have been utilized in a preclinical setting. We propose that large animal models with certain pathologies or age range may provide more clinically relevant platforms for testing TEVs and facilitate the clinical translation of tissue engineering technologies by increasing the likelihood of success in clinical trials.