Preclinical In-Vivo Assessment of Tissue Engineered Vascular Grafts and Selection of Appropriate Animal Models
Worldwide the population affected by cardiovascular diseases is increasing. Among others, vascular occlusion due to atherosclerosis is the major underlying mechanism. Surgical revascularization therapies are often indicated and require sufficient vascular substitutes with long-term function. Autologous vessels such as the saphenous vein or internal thoracic artery are still the gold standard for small diameter revascularizations like coronary artery bypass procedures. Unfortunately these vessels are often not available or of poor quality due to concomitant disease. Alternative vascular grafts are needed to overcome these limitations. Significant advances have been made in the development of tissue-engineered conduits over the last decades showing impressive results especially when these conduits were applied in young patients in high-flow, low-pressure vascular applications. Clinical studies are also currently ongoing showing successful application of tissue engineered vascular grafts (TEVGs) in adults as arteriovenous shunt grafts for dialysis access.
TEVGs are classified as tissue engineered medicinal products. Currently new regulatory approaches for tissue-engineered products are defined to comply with safety issues and to guarantee consistent product quality. Preclinical testing in adequate animal models is an important part of these evaluations to assess safety and functionality of cardiovascular tissue engineered devices to predict successful long-term clinical application.
The selection of the most appropriate animal model is an important consideration for significant preclinical trials because there are important variables between the different animal species. Small and large animals have been assigned to different graft testing procedures. To simulate, all the challenges to the implant after human application knowledge of comparative anatomy and physiology of the animal model is of utmost importance. Although no unique ideal animal model for all requirements of vascular graft testing exists, there are a number of animal species, which can be used for different test settings. Appropriate interpretation of test results based on relevant knowledge of species-dependent characteristics will help to assess preclinical biocompatibility of TEVGs and to predict potential harm for the patient as far as possible.
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