Regeneration of Blood Vessels

Cardiovascular disease is the leading cause of mortality in today’s world, necessitating the development of vascular substitutes with long-term patency [85]. Common disorders are connected with the stenosis or occlusion of blood vessels result in tissue damage and reduced blood flow because of inadequate nutrientsupply. Although autologous vessels such as internal thoracic artery and the saphenous vein represent the gold standard for small diameter grafts, patients do not have a vessel suitable for use because of vascular disease, amputation, or previous harvest [86]. The development for vascular materials has far been a half-century endeavor. Synthetic vascular grafts are also available as an alternative to autologous vessels. While large diameter (>6 mm) synthetic vascular grafts are successfully used to bypass arteries in high flow regions (e.g. the thoracic and abdominal aorta) [87], grafts with a small diameter (<6 mm) fail earlier because of thrombus formation and intimal hyperplasia [88].

Vascular graft failures are most commonly result from intimal hyperplasia, atherosclerosis, thrombosis, or infection. The absence of ECs lining the graft lumen can result in thrombosis, leading to the activation of clotting mechanisms and the adherence of blood proteins [89]. Intimal hyperplasia attributed to the migration of VSMCs from the vessel media to the intima. Intimal hyperplasia may happen in the native vessel or in the graft vessel around the anastomosis [86]. There are multiple causes, including (1) compliance mismatch between native vessel and the graft; (2) damage to, or a lack of ECs; (3) vessel diameter mismatch; (4) hemodynamic factors

Biomaterials, stem cells, and bioreactors for tissue engineering vascular grafts

Fig. 6.9 Biomaterials, stem cells, and bioreactors for tissue engineering vascular grafts. Mesenchymal stem cells from various sources such as hair follicles (HF), adipose tissue (AT), bone marrow (BM), or iPSC have been developed to generate functional vascular tissue. Small intestinal submucosa (SIS) was combined with fibrin glue to embed HF-MSC or BM-MSC into the vascular wall. The tissue engineering vascular grafts were subjected to pulsatile pressure and shear stress in a dynamic bioreactor after seeding with ECs [87] (Copyright permission from Elsevier Science Ltd)

causing blood flow disturbances; (5) trauma during surgery; and (6) suture line stress concentrations [90-95]. The main cause of graft failure after 1 year is atherosclerosis [96]. Atheroma formation is connected with the same factors as in the native arteries and happens through a similar process [86]. The vessel neointima was invaded by monocytes and result in the generation of atherosclerotic plaque [97, 98].Graft infection is very common in synthetic grafts, which can release toxins and give rise to chronic inflammation, resulting in sepsis and an astomotic rupture or failure [99-101].

To address this, a tissue-engineered vascular graft (TEVG) presents an attractive potential solution for the future of vascular surgery (see Fig. 6.9) [87]. A tissue- engineered vessel with the ability to grow, remodel, and repair in vivo, has clear advantages and would be of great benefit [86]. Thus, the development of tissue- engineered blood vessels has gained much attention in the field of vascular tissue engineering. The aim of vascular tissue engineering is to develop biological vascular tissues with functional properties of native vessels, combining various cells with biodegradable scaffolds. Three tissue engineering process are developed to regenerate blood vessels: in vivo, in vitro, and in situ. For in vitro vascular tissue engineering, cells, scaffolds and bioreactors are used to construct functional vascular tissues outside the body. In vivo vascular tissue engineering is a process that the tissue environment of the body is used as a bioreactor to generate an autologous vascular tissue. For in situ vascular tissue engineering, aacellular vascular graft is fabricated and a blood vessel is generated with the host cells to avoid the in vitro culture time period in situ. In situ vascular tissue engineering is a promising process to generate blood vessels since it can reduce the in vitro cultivation time and makes the grafts available off-the-shelf [86].

As an integrated part of the vascular network, a TEVG must satisfy a number of design criteria to be fit for purpose [102]. Fundamentally, it must possess appropriate mechanical properties, including the ability to withstand long-term hemodynamic stress, physiological compliance, and no susceptibility to permanent creep [103-106]. In addition, the graft should also be biocompatible, ie, nonimmunogenic, nonthrombogenic, and resistant to infection. In addition, the graft should possess appropriate water permeability [106]. Additionally, a TEVG should be suitable for implantation; with kink resistance and the ability to be sutured, manipulated, and handled. Ultimately, the graft should be able to remodel, grow, and self-repair in vivo [86].Although different methods try to meet these criteria, three factors are necessary: (1) a biocompatible elastic component to provide recoil and prevent aneurysm formation; (2) a nonactivated, confluent endothelium to prevent thrombosis; (3) a biocompatible component with high tensile strength to provide mechanical support [106, 107].

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