Blood Vessel Engineering - Requirements And Techniques

Introduction:

Patients with cardiovascular diseases undergo several vascular interventions, such as bypass grafting and angioplasty (a procedure to widen the narrow vessels) with or without a stent. Many patients do not have the required blood vessels, causing autograft difficulty. Many cardiac, peripheral, and cerebral vessels have a diameter of less than six-millimeter. Patients with vascular disorders have reduced availability of autologous (collecting from the same individual) blood tissues for small-sized (diameter less than six millimeters) blood vessel replacement. Synthetic polymer grafts with small diameters are prone to rapid thrombus formation, risk of bacterial colonization, intimal hyperplasia, neointimal hyperplasia, graft infection, and lastly, graft failure. Due to these limitations, tissue-engineered blood vessels were developed and have the capability to grow, provide a vasoactive response, remodel, and provide anti-coagulant, anti-platelet, and pro-fibrinolytic properties to reduce restenosis (reduction in the size of the vessel) and thrombogenesis (formation of blood clot).

What Is Blood Vessel Engineering?

Blood vessel engineering is a method of generating a bio-compatible vessel graft along with growth potentials. It has advantages such as the capability to grow, provide a vasoactive response, remodel, provide anti-coagulant, anti-platelet, and pro-fibrinolytic properties and reduce restenosis (reduction in blood vessel size) and thrombogenesis (formation of blood clot).

What Are The Requirements In Blood Vessel Tissue Engineering?

The mechanical requirements include:

• The engineered blood vessel should be able to withstand the burst pressure and should resist catastrophic rupture or tearing of the vessel. The average pressure of arterial circulation is 100 millimeters of mercury, the femoral artery is 250 millimeters of mercury, and cerebral vasculature is 60 to 100 millimeters of mercury. Therefore the tissue-engineered blood vessel should withstand a step higher than the maximum physiologic pressure.

• It should be resistant to fatigue.

• High suture retention and should be able to withstand the force required to dislodge the suture.

The biological requirements include:

• It should resist the acute response to blood-material interactions, which can lead to thrombosis due to non-specific protein adsorption.

• It should not undergo biodegradation or should not form scar tissue.

• It should not cause any infection.

• Hydrophobic materials can cause the adsorption of blood protein. Therefore hydrophilic materials should be used to resist blood protein adsorption, along with a luminal layer of endothelial cells. The use of endothelial cells can promote anti-coagulant, anti-platelet, and pro-fibrinolytic properties.

• The vascular grafts should undergo neo-endothelialization, which is done by including CD34 antibody, which is conjugated to graft surfaces, plasma treatment of graft surfaces, and use of stromal-derived factor-1 (SDF-1), which induces endothelial progenitor cells to migrate from the bone marrow. Endothelial cells also play an important role in being biocompatibility with blood-contacting materials. The use of endothelial cell seeding grafts has limited proliferative potential, but the use of luminal endothelial cells seeding grafts and smooth muscle cells seeding grafts have shown improved host integration, medial cellularization, and increased medial contractility. Choosing a correct phenotype of smooth muscle cells can prevent intimal hyperplasia and medial thickening.

• It should not produce an immune response to surgical trauma.

• It should not undergo a foreign body reaction.

• The graft should not undergo acute or chronic rejection. This is achieved by incorporating bioactive materials and biomimetic moieties such as glycosaminoglycans, elastin, and collagen.

• The graft should maintain a non-inflammatory environment. This can be achieved by using decellularized matrice, which can promote healing and resolution. The use of bone marrow mesenchymal stem cells can reduce immune and inflammatory responses.

• It should be hemocompatible (measurement of the thrombotic response of blood to a material), vasoactive, and should contain cell-supportive properties.

• It should be cytocompatible (should not harm the cells).

• It should mimic the immune response. This is achieved by using secretion products of inflammatory cells like neutrophils and macrophages.

What Are The Techniques That Are Used In Blood Vessel Engineering?

There are various methods, such as;

• Use Of Collagen And Other Biopolymers: Collagen gel cultured with smooth muscle cells and endothelial cells which contains a biologically active endothelial cell luminal surface, can be used, but it requires additional use of dacron mesh to withstand the high burst pressure. Using intracellular biomolecules and matrix components improves mechanical strength. Fibrin is an alternative biopolymer that can help in wound healing. Fibrin-collagen composites have higher gel compaction and strength compared to collagen alone. Fibrin gels can simulate smooth muscle cells to produce elastin, which is an important part of the artery wall; fibrin-based approaches require the addition of growth factors.

• Use Of Biodegradable And Bioresorbable Synthetic Polymers: Biodegradable materials such as polyglycolic acid, polylactic acid polycaprolactone, polyurethanes, and related composites and copolymers are used. These are pre-seeded with cells by using dynamic seeding, electrostatic seeding, or vacuum-aided seeding. But the use of biodegradable systems can amplify stress and compromise strength because of the absence of organized extracellular elastin sheets and smooth muscle cell contractility. Bioresorbable vascular grafts are used in host cells along with host-mediated degradation systems like oxidation, hydrolysis, and enzymolysis.

• Cell-Sheet Tissue Engineering: These blood vessels are engineered from secreted matrix proteins and autologous cells (collected from the same individual). This uses decellularized internal membrane obtained from a fibroblast sheet, a seeded endothelial layer, and a living adventitial layer. This method has shown success when used as arteriovenous fistulas in the case of high-risk patients.

• Use Of Decellularized Tissue Scaffolds: This technique uses the patient’s own extracellular matrix proteins, therefore providing structural integrity and cell growth.

• Advanced Biofabrication Technique (3D Bioprinting): This method creates a three-dimensional object by using layers of material with the help of computer-aided design models. This technique can produce complex functional heterocellular structures along with precision cell deposition and anatomical morphology. The technology which is used here is microextrusion based-bioprinting. Another technique, called the coaxial technique, can construct a multilayer blood tissue easily and quickly; this is the most advanced method.

Conclusion:

The blood vessel which is engineered should function all the biological factors, such as preventing thrombosis, foreign body reaction, and inflammatory reaction, and mechanical factors, such as withstanding burst pressure, strong suture retention, and preventing mechanical mismatch.