Trends in Biotechnology
ReviewFabricating Organized Elastin in Vascular Grafts
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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2021, Advanced Drug Delivery ReviewsCitation Excerpt :Moreover, once sufficient tissue is deposited and scaffold has been resorbed, it is essential that the inflammation is resolved and that the newly formed tissue is remodelled into a native-like organisation. Tissue maturation encompasses several processes, including the switch from activated myofibroblasts into a quiescent state [120], a transition of a matrix of primarily collagen 3 into a to collagen 1-dominated matrix [102,121,122], collagen reorganisation according to the hemodynamic demand [123], endothelialisation [15], and elastic fiber regeneration, although the latter is still largely elusive [124]. During this tissue maturation phase, IL-10-induced regulatory M2 macrophages play an important role, as they secrete tissue remodeling factors, such as matrix metalloproteinases (MMPs), and govern the resolution of both inflammation and myofibroblast activation by further secretion of key regulatory cytokines, including IL-10 [125].
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