Review
Fabricating Organized Elastin in Vascular Grafts

https://doi.org/10.1016/j.tibtech.2020.09.003Get rights and content

Highlights

  • 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.

Section snippets

The Lack of Organized Elastin in Vascular Grafts

The annual mortality associated with cardiovascular disease worldwide is expected to increase from 17.5 million in 2012 to 22.2 million in 2030 [1]. Patients often suffer from narrowing or blockage of the aorta, coronary artery, and peripheral arteries, which leads to ischemia in downstream tissues due to insufficient blood supply. Current treatments include angioplasty (see Glossary) and stent insertion to mechanically widen the constricted blood vessel or the implantation of vascular grafts

Elastogenesis in Arterial Development: From Tropoelastin to Organized Elastin

Elastogenesis refers to the process of forming elastic fibers from tropoelastin. Tropoelastin is the soluble monomeric precursor of the protein polymer elastin, which is the main component of elastic fibers, elastic lamellae, IEL, and EEL [20]. In vivo, elastic fiber assembly (Figure 2A) starts with the production of tropoelastin within the elastogenic cells. The protein is then transferred to the cell surface where it is aggregated with glycosaminoglycans (GAGs) and accumulates through

Limited Synthesis of Organized Elastin in Implanted Biodegradable Vascular Grafts

Biodegradable, polymer-based grafts have been shown to support elastin synthesis in vivo through stepwise polymer degradation and tissue remodeling processes that are mediated by the immune response (Figure 2B) [30., 31., 32., 33., 34., 35.]. Immediately after implantation, an early provisional matrix that contains mitogens, chemoattractants, cytokines, and growth factors forms on the vascular graft lumen surface. Matrix formation is followed by an acute inflammation phase, and the influx of

Incorporating Organized Elastin in Vascular Grafts Pre-implantation

As a result of limited organized elastin generation within grafts following in vivo implantation, researchers have sought to incorporate elastin directly into the vessels pre-implantation in an attempt to reproduce the native elastic structures found in arteries. Approaches currently under investigation include preseeding grafts with SMCs that are then stimulated to generate elastic fibers de novo, incorporation of engineered synthetic elastin into grafts, and the use of decellularized

Concluding Remarks and Future Perspectives

Regenerating the complex architecture and function of an artery from a biodegradable vascular graft is greatly limited by inadequate de novo production of organized elastin postimplantation. Implanted vascular grafts rely on immune response-facilitated remodeling for polymer degradation and ECM production, and current evidence indicates that limited elastin is produced. The lack of continuous elastic fibers, elastic lamella, and elastic lamina in vascular grafts likely contributes to multiple

Acknowledgements

Z.W. acknowledges an Australian Commonwealth Government Research Training Program Tuition Fee Offset and Stipend Scholarship. A.S.W. acknowledges funding from the National Health and Medical Research Council.

Disclaimer Statement

A.S.W. is the founding scientist of Elastagen Pty. Ltd., now sold to Allergan, Inc., an Abbvie company.

Glossary

Angioplasty
the use of a balloon catheter to widen a narrowed blood vessel and restore normal blood flow.
Coacervation
the spontaneous association of tropoelastin monomers into larger aggregates on the cell surface.
Compliance
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.
Elastic arteries
large conducting vessels emerging from the heart that

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