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

Abstract

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.

Extracellular matrix-mimetic poly(ethylene glycol) hydrogels engineered to regulate smooth muscle cell proliferation in 3-D

“…This suggests that the incorporation of heparin into gels could show promise to regulate excessive SMC proliferation and, further, inhibit the development of intimal hyperplasia. Besides heparin, a variety of bioactive factors have been reported to affect SMC proliferation [4,5]. For example, the growth factors in the culture medium (Section 2.7), such as basic fibroblast growth factor, epidermal growth factor, and insulin, have been reported to promote SMC proliferation [4,5].…”

“…The use of autologous bypass grafts, such as saphenous veins, remains one of the mainstays of treatment for advanced CVD. Owing to the limited availability of suitable autologous vessels, tissue engineered blood vessels (TEBVs) have emerged as an attractive alternative for bypass grafts [1][2][3][4]. In the development of TEBVs, smooth muscle cell (SMC) proliferation, along with deposition of extracellular matrix (ECM) in vascular media, is necessary for vessel wall construction and biomechanical functionality as blood conduits [4,5].…”

“…Owing to the limited availability of suitable autologous vessels, tissue engineered blood vessels (TEBVs) have emerged as an attractive alternative for bypass grafts [1][2][3][4]. In the development of TEBVs, smooth muscle cell (SMC) proliferation, along with deposition of extracellular matrix (ECM) in vascular media, is necessary for vessel wall construction and biomechanical functionality as blood conduits [4,5]. However, excessive SMC proliferation, if uncontrolled, will promote the development of intimal hyperplasia, which is one of the major failure mechanisms for current synthetic vascular grafts [6].…”

Vascular Grafting Strategies in Coronary Intervention

“…Poly(ethylene terephthalate) (PET®, Dacron), expanded poly(tetrafluoroethylene) (ePTFE, Gore-Tex®), and heparinbonded ePTFE (Propaten®) have demonstrated some degree of success as peripheral vascular grafts for larger vessel diameters due to high flow rates of blood past the luminal surface (Kapadia et al, 2008). In smaller diameter vessels (3-6 mm), early graft occlusion is frequently encountered, resulting from thrombogenicity of the synthetic surface and anastomotic hyperplasia (Chan-Park et al, 2009). Thrombus formation on the surface of a biomaterial is dictated by the Vroman effect of protein adsorption upon injury following implantation.…”

Construction of Small-Caliber, Polydiaxanone Cyclohexanone Vascular Stents

“…However, most types of grafts are not suitable for use with small arteries due to poor antiangiothrombicity, inconsistent material types, and low long-term graft strength [1][2][3][4]. For instance, two commonly used vascular prosthesis materials, viz Dacron and expanded polytetrafluoroethylene (ePTFE) [5], are not suitable for small-diameter vascular grafts (\5 mm), due to their poor resilience, compliance, and increased likelihood of thrombosis [6][7][8].…”