Biomimetic control of vascular smooth muscle cell morphology and phenotype for functional tissue-engineered small-diameter blood vessels

Small-diameter blood vessel substitutes are urgently needed for patients requiring replacements of their coronary and below-the-knee vessels and for better arteriovenous dialysis shunts. Circulatory diseases, especially those arising from atherosclerosis, are the predominant cause of mortality and morbidity in the developed world. Current therapies include the use of autologous vessels or synthetic materials as vessel replacements. The limited availability of healthy vessels for use as bypass grafts and the failure of purely synthetic materials in small-diameter sites necessitate the development of a biological substitute. Tissue engineering is such an approach and has achieved promising results, but reconstruction of a functional vascular tunica media, with circumferentially oriented contractile smooth muscle cells (SMCs) and extracellular matrix, appropriate mechanical properties, and vasoactivity has yet to be demonstrated. This review focuses on strategies to effect the switch of SMC phenotype from synthetic to contractile, which is regarded as crucial for the engineering of a functional vascular media. The synthetic SMC phenotype is desired initially for cell proliferation and tissue remodeling, but the contractile phenotype is then necessary for sufficient vasoactivity and inhibition of neointima formation. The factors governing the switch to a more contractile phenotype with in vitro culture are reviewed.