Fabricating Organized Elastin in Vascular Grafts

A lack of elastin contributes to vascular graft failure modes, including aneurysm, thrombosis, and intimal hyperplasia. Organized elastin synthesis during vascular graft remodeling is limited. De novo elastin production can be stimulated in vitro by using elastogenic smooth muscle cells in combination with the use of biochemical molecules and biomechanical stimuli. Continuous elastic fiber regeneration can be promoted by providing biaxial biomechanical stimulation. Elastin-based recombinamer-functionalized vascular grafts prevent thrombosis and promote endothelium formation. Tropoelastin can be stabilized by heating and incorporated into vascular grafts as a structural component to provide elasticity. Elastic lamina can be extracted without other extracellular matrix components, and decellularized internal elastic lamina is a functional blood-contacting surface. Surgically bypassing or replacing a severely damaged artery using a biodegradable synthetic vascular graft is a promising treatment that allows for the remodeling and regeneration of the graft to form a neoartery. Elastin-based structures, such as elastic fibers, elastic lamellae, and laminae, are key functional components in the arterial extracellular matrix. In this review, we identify the lack of elastin in vascular grafts as a key factor that prevents their long-term success. We further summarize advances in vascular tissue engineering that are focused on either de novo production of organized elastin or incorporation of elastin-based biomaterials within vascular grafts to mitigate failure and enhance enduring in vivo performance. Surgically bypassing or replacing a severely damaged artery using a biodegradable synthetic vascular graft is a promising treatment that allows for the remodeling and regeneration of the graft to form a neoartery. Elastin-based structures, such as elastic fibers, elastic lamellae, and laminae, are key functional components in the arterial extracellular matrix. In this review, we identify the lack of elastin in vascular grafts as a key factor that prevents their long-term success. We further summarize advances in vascular tissue engineering that are focused on either de novo production of organized elastin or incorporation of elastin-based biomaterials within vascular grafts to mitigate failure and enhance enduring in vivo performance. the use of a balloon catheter to widen a narrowed blood vessel and restore normal blood flow. the spontaneous association of tropoelastin monomers into larger aggregates on the cell surface. the ability of a vascular graft to expand and contract elastically in response to a pulsatile luminal pressure. This is measured by the percent change of diameter between systolic and diastolic pressure. large conducting vessels emerging from the heart that contain layers of elastic lamellae in the tunica media that respond elastically to high blood pressure. Examples of elastic arteries include the aorta and the pulmonary arteries. the ability of the vascular graft to resume its nominal diameter after expansion in response to the pulsatile luminal pressure. bundles of elastin associated with microfibrils. concentrically aligned fenestrated sheets composed of elastic fiber networks. a key ECM protein that gives rise to the elasticity of tissues. long polypeptides containing repetitive natural elastin domains that are fabricated through recombinant DNA technology. the process of fabricating fibrous scaffolds by using electrostatic force to draw fine polymer fibers onto a substrate for collection. a 3D, non-cellular network that contains proteins, proteoglycans, and non-proteoglycan polysaccharides and provides structural support and biochemical cues to cells. glycoproteins that are a major component of the microfibrils in elastic fibers. glycoproteins that are present in the elastic fiber and interact with various components of the basement membrane and ECM. a drying process that can be used to form pores in a scaffold by removal of its frozen water content through sublimation. a process used to form pores in a scaffold by saturating the scaffold with gas under high pressure then releasing the pressure to allow nucleation and growth of air bubbles within the scaffold. pluripotent stem cells that are reprogrammed from somatic cells in adult tissues. They can differentiate into all types of cells in the human body. Production of induced pluripotent stem cells bypasses the use of embryos for stem cell isolation and has patient-specific applications in regenerative medicine that are free from the risk of immune rejection. the thickening of the tunica intima caused by the over proliferation of arterial SMCs. a family of copper-dependent enzymes that oxidizes lysine residues in tropoelastin in order to facilitate crosslinking of tropoelastin monomers to form polymeric elastin. multipotent stromal cells that are isolated from tissues such as bone marrow and adipose tissue. They can differentiate into more than one type of cell in the human body, including bone, fat, and cartilage cells, but are more limited than pluripotent stem cells. arteries that follow on from the elastic arteries and distribute blood to different parts of the body. Examples of muscular arteries include coronary, carotid, axillary, and palmar arteries. an ECM that is rich in fibrin and plasma fibronectin. tropoelastin produced in an expression host and used as a highly purified protein. a process used to form pores in a scaffold by mixing salt and a polymer solvent and then allowing the solvent to evaporate. Subsequent salt removal through dissolution in water produces pores. the soluble protein monomer of elastin produced by elastogenic cells.