Open Access is an initiative that aims to make scientific research freely available to all. To date our community has made over 100 million downloads. It’s based on principles of collaboration, unobstructed discovery, and, most importantly, scientific progression. As PhD students, we found it difficult to access the research we needed, so we decided to create a new Open Access publisher that levels the playing field for scientists across the world. How? By making research easy to access, and puts the academic needs of the researchers before the business interests of publishers.
We are a community of more than 103,000 authors and editors from 3,291 institutions spanning 160 countries, including Nobel Prize winners and some of the world’s most-cited researchers. Publishing on IntechOpen allows authors to earn citations and find new collaborators, meaning more people see your work not only from your own field of study, but from other related fields too.
To purchase hard copies of this book, please contact the representative in India:
CBS Publishers & Distributors Pvt. Ltd.
www.cbspd.com
|
customercare@cbspd.com
School of Molecular Bioscience, University of Sydney, Australia
Anthony Weiss*
School of Molecular Bioscience, University of Sydney, Australia
*Address all correspondence to:
1. Introduction
Elastin is a key structural protein found in the extracellular matrix (ECM) of all mammals. As the dominant part of the elastic fiber, elastin confers the mechanical properties of resilience and elasticity essential to the function of elastic tissues. Elastin interacts with cells through specific biochemical mechanisms. This chapter considers the (1) mechanical and biochemical roles of elastin in elastic tissues and the subsequent disease phenotypes that result from the degradation and loss of elastin, (2) development and success of current elastin based biomaterials including sources of elastin for tissue engineering and their application, and (3) vascular constructs that our laboratory has developed from recombinant human tropoelastin. These constructs mimic the physical and biochemical properties of native elastin.
Elastin is formed in the process of elastogenesis through the assembly and cross-linking of the protein tropoelastin (Figure 1). The tropoelastin monomer is produced from expression of the elastin gene during perinatal development by elastogenic cells such as smooth muscle cells (SMCs), endothelial cells, fibroblasts and chondroblasts (Uitto, Christiano et al. 1991). The tropoelastin transcript undergoes extensive alternative splicing leading to the removal of entire domains from the protein. In humans, this splicing results in several tropoelastin isoforms, the most common of which lacks exon 26A (Indik, Yeh et al. 1987). Mature, intracellular tropoelastin associates with the elastin binding protein (EBP) and this complex is secreted to the cell surface (Hinek 1995). Competition from galactosides results in the dissociation of EBP from tropoelastin and the return of EBP to the cell (Mecham 1991). Released tropoelastin on the cell surface subsequently aggregates by coacervation. During this process, the hydrophobic domains of tropoelastin associate and tropoelastin molecules become concentrated and increasingly aligned allowing for subsequent formation of cross-links (Vrhovski, Jensen et al. 1997).
Coacervated tropoelastin is deposited onto microfibrils which probably serve as a scaffold to direct tropoelastin cross-linking and consequential elastic fiber formation. Cross-linking is facilitated by the enzyme lysyl oxidase, which deaminates lysine side chains in tropoelastin to form allysine sidechains that can subsequently react with adjacent allysine or lysine side chains to form cross-links (Kagan and Sullivan 1982). These cross-links can then further react to form desmosine and isodesmosine cross-links between tropoelastin molecules (Umeda, Nakamura et al. 2001). Multiple cross-links result in the mature insoluble elastic fiber.
Figure 1.
Schematic of the stages of elastogenesis.(i) Tropoelastin is transcribed and translated from the elastin (ELN) gene and (ii) transported to the plasma membrane in association with EBP. (iii) Tropoelastin is released and aggregates on the cell surface, while EBP disassociates to form a complex with available galactosides. (iv) Tropoelastin aggregates are oxidized by lysyl oxidase leading to cross-linked elastin that accumulates on microfibrils which help to direct elastin deposition. (v) The process of deposition and cross-linking continues to give rise to mature elastic fibers
Elastin plays a key structural role in elastic tissues including arteries, skin, ligament, cartilage and tendons (Sandberg, Soskel et al. 1981). As the dominant part of the elastic fiber, elastin confers resilience and elasticity essential to the function of these tissues. The arrangement of elastin in the ECM varies between different tissues to yield a wide range of structures with tailored elastic properties. For example, elastin in the form of thin lamina in the arterial wall is mostly responsible for the strength and elasticity necessary for vessel expansion and regulation of blood flow (Glagov, Vito et al. 1992). In the lung, elastin is arranged as a latticework that helps to support the opening and closing of the alveoli (Starcher 2001). In skin, elastin fibers are enriched in the dermis where they impart skin flexibility and extensibility (Roten, Bhat et al. 1996; Pasquali-Ronchetti and Baccarani-Contri 1997).
3.1. Mechanical properties of elastin
Elastin is extremely durable protein with a mean residence time of 74 years (Shapiro, Endicott et al. 1991). It comprises almost 90% of the elastic fiber where it dominates its elastic, mechanical properties. The Young’s modulus for elastic fibers typically ranges from 300 - 600 kPa although it can measure as low as 100 kPa for arterial elastin, highlighting the versatile nature of these structures within the ECM (Mithieux and Weiss 2005; Zou and Zhang 2009). Although the mechanism for elasticity has not been fully elucidated, elastic recoil likely to be entropically driven whereby extension of the protein results in a more ordered structure and thus recoil occurs so the protein can return to a disorder state (reviewed by (Rosenbloom, Abrams et al. 1993; Vrhovski and Weiss 1998). This elasticity is due to the inherent elastic properties of the monomer (Holst, Watson et al. 2010; Baldock, Oberhauser et al. 2011).
Schematic of human tropoelastin primary organization and binding partners.All domains are shown. Exons 13, 22, 23, 26A and 32 are subject to alternate splicing
Disease phenotypes manifest due to the degradation and loss of elastin through injury, genetic mutation or age. For example, autosomal dominant and recessive forms of cutis laxa mutations can arise from genetic modifications to the elastin gene and impaired vesicular trafficking, and have been reviewed elsewhere (e.g. (Hucthagowder, Morava et al. 2009; Callewaert, Renard et al. 2011). In skin, the loss of elastin in the dermal layers in severe burns leads significant physical injuries including scarring, wound contraction and loss of skin extensibility (Rnjak, Wise et al. 2011). In the vasculature, genetic mutations in the elastin gene or genes associated with elastic fiber formation result in severe, debilitating diseases (reviewed by (Kielty 2006)). Supravalvular aortic stenosis can arise from point mutations, deletions or translocations within the elastin gene that typically lead to haploinsufficiency and an altered organization of elastic lamellae in the artery, SMC hyperproliferation, increased media thickness and obstruction of the aorta (Urban, Zhang et al. 2001). Elastin is also associated with several vascular pathologies. Damage and fragmentation of elastin in the artery have been linked with deregulation of SMC phenotype, SMC hyperproliferation and invasion which cause vessel occlusion and cardiovascular complications (Brooke, Bayes-Genis et al. 2003). The failure of inelastic materials as arterial replacements further indicate the essential need for intact elastin in functional arteries (Abbott, Megerman et al. 1987).
Common to all elastin diseases is the catalogued in vivo inability to adequately regenerate and repair dysfunctional elastic fibers leading to subsequent failure of tissue function. This deficiency is mostly attributed to exclusive expression of elastin during early development (Mecham 1991), which results in poor renewal of elastin in adult tissues. Materials that can serve as elastin replacements in adult tissues are in demand. This demand is most apparent in vascular tissue engineering as cardiovascular disease is the major contributor to adult mortality worldwide (Lloyd-Jones, Adams et al. 2010). Current synthetic vascular biomaterials, particularly expanded polyterafluoroethylene (ePTFE) and polyethylene terephthalate (Dacron) are poorly mismatched to native arteries in terms of mechanical properties, endothelial cell and SMC interactions and thrombogenecity which lead to a high failure rate in patients (Chlupac, Filova et al. 2009). Elastin can restore properties that are deficient in current grafts, including compliance and strength to match native vessels and regulation of endothelial and smooth muscle cells.
Decellularized tissues, generated by the removal of the cellular components of tissue explant are useful as biomaterials as they a priori possess much of the complex architecture of the native ECM. Elastic tissues are particular amenable to this method as the stability and insolubility of the elastin protein means it is resistant to many treatments used during decellularization processes.
Decellularizing elastin-rich tissues have been proposed as a path towards the potential replacement of artery, heart valves, bladder skin and lung (Daamen, Veerkamp et al. 2007; Petersen, Calle et al. 2010; Price, England et al. 2010). Enriched elastin vascular grafts generated by decellularization and removal of collagen with proteases from porcine carotid arteries can support fibroblasts in vitro (Chuang, Stabler et al. 2009). Cell infiltration has also been observed for other decellularized vascular constructs in vitro and in vivo (Schmidt and Baier 2000; Conklin, Richter et al. 2002; Dahl, Koh et al. 2003; Uchimura, Sawa et al. 2003). Skin replacements formed from decellularized porcine dermis containing 30% elastin show vascularization and support of cultured keratinocytes when examined in a rat excision model. Degradation of the collagen component of the material also occurs (Hafemann, Ensslen et al. 1999). Transplant of a repopulated decellularized human trachea demonstrates the feasibility of acquiring functionality and improved mechanical capabilities in a patient after 4 months (Macchiarini, Jungebluth et al. 2008).
Despite these advantages, decellularized tissue sources are generally animal derived and are therefore restricted in shape, size and supply. Additionally, decellularization methods involve chemical, physical or enzymatic treatments that can individually or collectively compromise mechanical and biological properties (Gilbert, Sellaro et al. 2006). The common use of detergents can limit the degree of cell repopulation. Decellularization methods are highly specific to a particular tissue thus their broader application to different tissues yields viable results in terms of remaining ECM structure and degree of decellularization (Gilbert, Sellaro et al. 2006). Lack of uniformity and versatility can limit the use of decellularized materials as commercial tissue replacements.
Elastin used for in vitro work is generally obtained by purifying the protein directly from elastin-rich tissues. Tissues are treated with chemicals such as NaOH or guanidine-HCl and/or high heat to remove other proteins and cellular material and leave insoluble elastic fibers. However extensive cross-linking and the consequential insolubility of elastin makes it difficult to manipulate in vitro (Daamen, Veerkamp et al. 2007).
The solubility of tissue-derived elastin can be improved by partial hydrolysis. A fragmented elastin preparation termed α-elastin is obtained by hydrolysis with oxalic acid and is often used in in vitro studies of elastin (Partridge, Davis et al. 1955). Hydrolysis can be performed with potassium hydroxide to yield κ-elastin or through mild digestion with proteinases (Partridge, Davis et al. 1955; Jacob and Hornebeck 1985). Hydrolyzed preparations of elastin display various properties that are similar to the native protein including temperature-induced aggregation (coacervation) and regulation of SMC and fibroblast phenotype (De Vries, Zeegelaar et al. 1995; Ito, Ishimaru et al. 1998). Fragmentation of elastin is associated with reduced protein structural integrity and altered cellular signaling properties (Daamen, Veerkamp et al. 2007; Bax, Rodgers et al. 2009).
Multiple vascular materials have been synthesized from hydrolyzed elastin preparations (Table 1). Hydrogels, cross-linked films and electrospun fibers containing hydrolyzed α-elastin all show preferable vascular material properties including regulation of SMC phenotype and increased mechanical elasticity. Electrospun materials are of particular interest as architecturally, these materials closely mimic the dimensions of elastic fibers in vivo (Li and Xia 2004).
Hydrolyzed elastin materials have also been proposed for use in the repair of elastic cartilage. In porous PCL scaffolds, infusion of α-elastin demonstrates enhanced scaffold elasticity and attachment and proliferation of articular cartilage chondrocytes in vitro (Annabi, Fathi et al. 2011). Replication of auricular-like cartilage has also been explored using alginate, collagen type I and κ-elastin containing hydrogels with auricular cartilage chondrocytes (de Chalain, Phillips et al. 1999). When these materials were implanted in mice and harvested after 12 weeks, matrix components including collagen and elastic fibers were present.
Dermal replacements containing hydrolyzed elastin demonstrate improved properties over elastin-free materials in regards to wound contraction and tissue regeneration (Rnjak, Wise et al. 2011). For example, MatriDerm, a collagen based scaffold with α-elastin shows improved skin elasticity (Ryssel, Gazyakan et al. 2008). Hydrogels formed exclusively from α-elastin (Figure 3) favorably support attachment and proliferation of dermal fibroblasts in vitro (Annabi, Mithieux et al. 2009; Annabi, Mithieux et al. 2009).
Scaffold
Advantages
Limitations
Reference
α-elastin film
-Low elastic modulus -attachment & proliferation of SMCs
-reduced SMC proliferation compared to TCPS
(Leach, Wolinsky et al. 2005)
elastin/gelatin gel
-Young’s modulus matched to native artery -proliferation & infiltration of SMCs
-reduced SMC growth compared to TCPS
(Lamprou, Zhdan et al. 2010)
Collagen type I gels containing α-elastin
-SMC proliferation inhibited
- EC proliferation inhibited at high α-elastin concentrations
-attachment & proliferation of embryonic mesenchymal cells
-complete 3D constructs not created
(Li, Mondrinos et al. 2005)
α-elastin, PLGA & gelatin electrospun sheet
-mechanical properties tuned to artery through polymer content -proliferation of ECs on scaffold surface & infiltration of SMCs. -expression of functional EC molecules
-mechanical properties tested on electrospun sheets, not tubes
(Han, Lazarovici et al. 2011)
α-elastin, collagen type I & PLGA electrospun conduit
-matched compliance to bovine iliac artery -proliferation of ECs on inner & SMCs on outer surface of conduit -no immune reaction when implanted in mice
-scaffold contraction in vitro
(Stitzel, Liu et al. 2006; Lee, Yoo et al. 2007)
α-elastin, collagen type I & PLLA, PCL or PLCL blended electrospun conduit
-growth of bovine ECs -infiltration and α-SMA expression of SMCs
-scaffold contraction of PLCL blends in vitro
(Lee, Yoo et al. 2007)
α-elastin & PDO blended electrospun conduit
-mechanical properties matched to femoral artery with increased elastin content -increased cell infiltration with increased elastin content -increased graft burst pressure with suture reinforcement
-suture reinforcement lowers compliance
(Sell, McClure et al. 2006; Smith, McClure et al. 2008)
Elastin, collagen type I & collagen type III tri-layered electrospun conduit
Synthetic human elastin hydrogels (A) formed from the cross-linking of rhTE and (B) after hydration in phosphate buffered saline. (C) Hydrogel surface porosity shown by scanning electron microscopy
Figure 5.
Synthetic elastin electrospun materials.Representative photographs of a synthetic human elastin scaffold (A) before cross-linking and (B-C) after cross-linking with hexamethylene diisocyanate and wetting with phosphate buffered saline. Uncross-linked scaffolds are stiff and inflexible while cross-linked scaffolds are highly flexible and collapse when not supported. Scanning electron micrographs of (D) uncross-linked electrospun fibers and (E) cross-linked electrospun fibers reveal the ribbon-like morphology of fibers
Three dimensional biomaterials are produced by cross-linking rhTE to form synthetic human elastin. Synthetic elastin has advantages over decellularized tissue and hydrolyzed elastin preparations as it utilizes human protein avoiding potential problems arising from species differences while benefiting from homogeneity to improve reproducibility and uniformity.
Figure 6.
Examples of synthetic elastin electrospun materials.Scanning electron micrographs of (A) human umbilical vein endothelial cells, (B) SMCs and (C) dermal fibroblasts cultured on synthetic elastin fibers
Electrospun synthetic elastin allows for the formation of highly organized biomaterials with tunable mechanical biological properties. Electrospun synthetic elastin is formed by the electrospinning and chemical cross-linking of rhTE to yield ribbon-like microfibers (Figure 5) whose dimensions match those of native elastin fibers (Nivison-Smith, Rnjak et al. 2010). Highly porous electrospun synthetic elastin scaffolds, generated by using high flow rates facilitate the infiltration of dermal fibroblasts in vitro and present an alternative to synthetic elastin hydrogels as a dermal replacement (Rnjak, Li et al. 2009).
As a potential vascular material, electrospun synthetic elastin shows attractive characteristics including internal mammary artery-matched elastic mechanical properties, low platelet adhesion (Wise, Byrom et al. 2011) and support of growing human vascular cells including SMCs, endothelial cells (Figure 6) and embryonic palatal mesenchymal stem cells (Li, Mondrinos et al. 2005; Nivison-Smith, Rnjak et al. 2010). Synthetic human elastin fibers can also direct cell spreading to resemble cell organization in vivo. For example, the radial alignment of SMC in the arterial media is mimicked by culture of these cells on parallel synthetic elastin fibers (Nivison-Smith & Weiss 2011, submitted). Blended conduits of synthetic elastin and silk or polycaprolactone display elasticity and cell adhesion properties courtesy of the rhTE component while the composite component confers additional mechanical strength (Hu, Wang et al. 2010; Wise, Byrom et al. 2011).
Elastin is an essential matrix protein, so it is logical that biomaterials designed for elastic tissues should incorporated elastin. Difficulties in sourcing pure intact elastin preparations, particularly those that reflect human sequences, has limited the generation of these materials. Synthetic human elastin that is made from rhTE presents a versatile and stable component of vascular and dermal materials. Elastin-based constructs demonstrate mechanical and biological properties consistent with native elastin and have potential for a wider range of applications.
We acknowledge grant support from the Australian Research Council and the National Health and Medical Research Council. We thank Dr. Anna Waterhouse for the images related to elastin hydrogels. We acknowledge the contributions of the staff and the facilities made available at the AMMRF (Australian Microscopy & Microanalysis Research Facility) at the Australian Center for Microscopy and Microanalysis, The University of Sydney.
References
1.AbbottW. M.MegermanJ.et al.1987Effect of compliance mismatch on vascular graft patency. J Vasc Surg52376382
2.AkhtarK.BroekelmannT. J.et al.2011Oxidative modifications of the C-terminal domain of tropoelastin prevent cell bindingJ Biol Chem.
4.AnnabiN.FathiA.et al.2011The effect of elastin on chondrocyte adhesion and proliferation on poly (varepsilon-caprolactone)/elastin composites. Biomaterials 32615171525
5.AnnabiN.MithieuxS. M.et al.2009Synthesis of highly porous crosslinked elastin hydrogels and their interaction with fibroblasts in vitro. Biomaterials302745504557
6.AnnabiN.MithieuxS. M.et al.2009The fabrication of elastin-based hydrogels using high pressure CO(2). Biomaterials 30117
7.AnnabiN.MithieuxS. M.et al.2010Cross-linked open-pore elastic hydrogels based on tropoelastin, elastin and high pressure CO2. Biomaterials 31716551665
8.BaldockC.OberhauserA. F.et al.2011Shape of tropoelastin, the highly extensible protein that controls human tissue elasticity. Proc Natl Acad Sci U S A1081143224327
9.BarbieC.AngibaudC.et al.1989Some factors affecting properties of elastin-fibrin biomaterial.Biomaterials107445448
10.BaxD. V.RodgersU. R.et al.2009Cell adhesion to tropoelastin is mediated via the C-terminal GRKRK motif and integrin alphaVbeta3. J Biol Chem284422861628623
11.BellinghamC. M.WoodhouseK. A.et al.2001Self-aggregation characteristics of recombinantly expressed human elastin polypeptides. Biochim Biophys Acta 15501619
12.BolandE. D.MatthewsJ. A.et al.2004Electrospinning collagen and elastin: preliminary vascular tissue engineering. Front Biosci914221432
13.BroekelmannT. J.KozelB. A.et al.2005Tropoelastin interacts with cell-surface glycosaminoglycans via its COOH-terminal domain. J Biol Chem280494093940947
14.BrookeB. S.Bayes-GenisA.et al.2003New insights into elastin and vascular disease. Trends Cardiovasc Med 135176181
15.BuijtenhuijsP.ButtafocoL.et al.2004Tissue engineering of blood vessels: characterization of smooth-muscle cells for culturing on collagen-and-elastin-based scaffolds. Biotechnol Appl Biochem 39(Pt 2): 141 EOF9 EOF
16.ButtafocoL.Engbers-BuijtenhuijsP.et al.2006First steps towards tissue engineering of small-diameter blood vessels: preparation of flat scaffolds of collagen and elastin by means of freeze drying. J Biomed Mater Res B Appl Biomater772357368
17.ButtafocoL.KolkmanN. G.et al.2006Electrospinning of collagen and elastin for tissue engineering applications. Biomaterials275724734
18.CallewaertB.RenardM.et al.2011New insights into the pathogenesis of autosomal-dominant cutis laxa with report of five ELN mutations. Hum Mutat324445455
19.ChlupacJ.FilovaE.et al.2009Blood vessel replacement: 50 years of development and tissue engineering paradigms in vascular surgery. Physiol Res 58 Suppl 2: S119139
20.ChuangT. H.StablerC.et al.2009Polyphenol-stabilized tubular elastin scaffolds for tissue engineered vascular grafts. Tissue Eng Part A 151028372851
21.ConklinB. S.RichterE. R.et al.2002Development and evaluation of a novel decellularized vascular xenograft. Med Eng Phys243173183
22.DaamenW. F.van MoerkerkH. T.et al.2003Preparation and evaluation of molecularly-defined collagen-elastin-glycosaminoglycan scaffolds for tissue engineering. Biomaterials242240014009
23.DaamenW. F.VeerkampJ. H.et al.2007Elastin as a biomaterial for tissue engineering. Biomaterials283043784398
24.DahlS. L.KohJ.et al.2003Decellularized native and engineered arterial scaffolds for transplantation. Cell Transplant126659666
25.de ChalainT.PhillipsJ. H.et al.1999Bioengineering of elastic cartilage with aggregated porcine and human auricular chondrocytes and hydrogels containing alginate, collagen, and kappa-elastin. J Biomed Mater Res 443280288
26.De VriesH. J.ZeegelaarJ. E.et al.1995Reduced wound contraction and scar formation in punch biopsy wounds. Native collagen dermal substitutes. A clinical study. Br J Dermatol 1325690697
27.Engbers-BuijtenhuijsP.ButtafocoL.et al.2005Analysis of the balance between proliferation and apoptosis of cultured vascular smooth muscle cells for tissue-engineering applications. Tissue Eng 11(11-12): 1631 EOF1639 EOF
28.FauryG.GarnierS.et al.1998Action of tropoelastin and synthetic elastin sequences on vascular tone and on free Ca2+ level in human vascular endothelial cells. Circ Res 823328336
29.FauryG.RistoriM. T.et al.1994Role of the elastin-laminin receptor in the vasoregulation. C R Acad Sci III 3179807811
30.FauryG.RistoriM. T.et al.1995Effect of elastin peptides on vascular tone. J Vasc Res 322112119
31.GilbertT. W.SellaroT. L.et al.2006Decellularization of tissues and organs. Biomaterials 271936753683
32.GlagovS.VitoR.et al.1992Micro-architecture and composition of artery walls: relationship to location, diameter and the distribution of mechanical stress. J Hypertens Suppl 10(6): S101104
33.HafemannB.EnsslenS.et al.1999Use of a collagen/elastin-membrane for the tissue engineering of dermis. Burns255373384
34.HanJ.LazaroviciP.et al.2011Co-electrospun blends of PLGA, gelatin, and elastin as potential nonthrombogenic scaffolds for vascular tissue engineering. Biomacromolecules122399408
35.HinekA.1995The 67 kDa spliced variant of beta-galactosidase serves as a reusable protective chaperone for tropoelastin. Ciba Found Symp192185191discussion 191-186.
36.HolstJ.WatsonS.et al.2010Substrate elasticity provides mechanical signals for the expansion of hemopoietic stem and progenitor cells. Nat Biotechnol281011231128
37.HornebeckW.TixierJ. M.et al.1986Inducible adhesion of mesenchymal cells to elastic fibers: elastonectin. Proc Natl Acad Sci U S A 831555175520
38.HuX.WangX.et al.2010Biomaterials derived from silk-tropoelastin protein systems. Biomaterials313281218131
39.HucthagowderV.MoravaE.et al.2009Loss-of-function mutations in ATP60A2impair vesicular trafficking, tropoelastin secretion and cell survival. Hum Mol Genet 18(12): 2149 EOF2165 EOF
40.IndikZ.AbramsW. R.et al.1990Production of recombinant human tropoelastin: characterization and demonstration of immunologic and chemotactic activity. Arch Biochem Biophys28018086
41.IndikZ.YehH.et al.1987Alternative splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA. Proc Natl Acad Sci U S A841656805684
42.ItoS.IshimaruS.et al.1997Inhibitory effect of type 1 collagen gel containing alpha-elastin on proliferation and migration of vascular smooth muscle and endothelial cells.Cardiovasc Surg52176183
43.ItoS.IshimaruS.et al.1998Effect of coacervated alpha-elastin on proliferation of vascular smooth muscle and endothelial cells. Angiology 494289297
44.JacobM. P.HornebeckW.1985Isolation and characterisation of insoluble and kappa-elastins. Methods of connective tissue research L. Robert, M. Moczar and E. Moczar. Basel, Karger. 492129
45.JungS.RutkaJ. T.et al.1998Tropoelastin and elastin degradation products promote proliferation of human astrocytoma cell lines. J Neuropathol Exp Neurol575439448
46.KaganH. M.SullivanK. A.1982Lysyl oxidase: preparation and role in elastin biosynthesis. Methods Enzymol 82 Pt A: 637650
47.KamisatoS.UemuraY.et al.1997Involvement of intracellular cyclic GMP and cyclic GMP-dependent protein kinase in alpha-elastin-induced macrophage chemotaxis. J Biochem 1215862867
48.KarnikS. K.BrookeB. S.et al.2003A critical role for elastin signaling in vascular morphogenesis and disease. Development 1302411423
49.KarnikS. K.WytheJ. D.et al.2003Elastin induces myofibrillogenesis via a specific domain, VGVAPG. Matrix Biol225409425
50.KeeleyF. W.BellinghamC. M.et al.2002Elastin as a self-organizing biomaterial: use of recombinantly expressed human elastin polypeptides as a model for investigations of structure and self-assembly of elastin. Philos Trans R Soc Lond B Biol Sci 3571418185189
51.KieltyC. M.2006Elastic fibres in health and disease. Expert Rev Mol Med819123
52.KoensM. J.FarajK. A.et al.2010Controlled fabrication of triple layered and molecularly defined collagen/elastin vascular grafts resembling the native blood vessel. Acta Biomater 61246664674
53.LammersG.TjabringaG. S.et al.2009A molecularly defined array based on native fibrillar collagen for the assessment of skin tissue engineering biomaterials. Biomaterials 303162136220
54.LamprouD.ZhdanP.et al.2010Gelatine and Gelatine/Elastin Nanocomposites for Vascular Grafts: Processing and Characterization. J Biomater Appl.
55.LeachJ. B.WolinskyJ. B.et al.2005Crosslinked alpha-elastin biomaterials: towards a processable elastin mimetic scaffold. Acta Biomater12155164
56.LeeS. J.YooJ. J.et al.2007In vitro evaluation of electrospun nanofiber scaffolds for vascular graft application. J Biomed Mater Res A8349991008
57.LiD.XiaY. N.2004Electrospinning of nanofibers: Reinventing the wheel? Advanced Materials161411511170
58.LiD. Y.BrookeB.et al.1998Elastin is an essential determinant of arterial morphogenesis. Nature3936682276280
59.LiM.MondrinosM. J.et al.2005Electrospun protein fibers as matrices for tissue engineering. Biomaterials263059996008
60.Lloyd-JonesD.AdamsR. J.et al.2010Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation 121(7): e46e215.
61.LongM. M.KingV. J.et al.1989Elastin repeat peptides as chemoattractants for bovine aortic endothelial cells. J Cell Physiol1403512518
62.MacchiariniP.JungebluthP.et al.2008Clinical transplantation of a tissue-engineered airway. Lancet 372965520232030
63.Mc ClureM. J.SellS. A.et al.2010A three-layered electrospun matrix to mimic native arterial architecture using polycaprolactone, elastin, and collagen: a preliminary study. Acta Biomater 6724222433
64.MechamR. P.1991Elastin synthesis and fiber assembly. Ann N Y Acad Sci 624137146
65.MithieuxS. M.RaskoJ. E.et al.2004Synthetic elastin hydrogels derived from massive elastic assemblies of self-organized human protein monomers. Biomaterials252049214927
66.MithieuxS. M.TuY.et al.2009In situ polymerization of tropoelastin in the absence of chemical cross-linking. Biomaterials304431435
67.MithieuxS. M.WeissA. S.2005Elastin. Adv Protein Chem70437461
68.MithieuxS. M.WiseS. G.et al.2005A model two-component system for studying the architecture of elastin assembly in vitro. J Struct Biol1493282289
69.MiyamotoK.AtarashiM.et al.2009Creation of cross-linked electrospun isotypic-elastin fibers controlled cell-differentiation with new cross-linker. Int J Biol Macromol 4513341
70.MochizukiS.BrassartB.et al.2002Signaling pathways transduced through the elastin receptor facilitate proliferation of arterial smooth muscle cells. J Biol Chem277474485444863
71.MuiznieksL. D.JensenS. A.et al.2003Structural changes and facilitated association of tropoelastin. Arch Biochem Biophys 4102317323
72.Nivison-SmithL.RnjakJ.et al.2010Synthetic human elastin microfibers: stable cross-linked tropoelastin and cell interactive constructs for tissue engineering applications. Acta Biomater62354359
73.PartridgeS. M.DavisH. F.et al.1955The chemistry of connective tissues. 2. Soluble proteins derived from partial hydrolysis of elastin. Biochem J6111121
74.Pasquali-RonchettiI.Baccarani-ContriM.1997Elastic fiber during development and aging. Microsc Res Tech384428435
75.PetersenT. H.CalleE. A.et al.2010Tissue-engineered lungs for in vivo implantation. Science3295991538541
76.PriceA. P.EnglandK. A.et al.2010Development of a decellularized lung bioreactor system for bioengineering the lung: the matrix reloaded. Tissue Eng Part A 16825812591
77.RnjakJ.LiZ.et al.2009Primary human dermal fibroblast interactions with open weave three-dimensional scaffolds prepared from synthetic human elastin. Biomaterials 303264696477
78.RnjakJ.WiseS. G.et al.2011Severe Burn Injuries and the Role of Elastin in the Design of Dermal Substitutes. Tissue Eng Part B Rev.
79.RodgersU. R.WeissA. S.2004Integrin alpha v beta 3 binds a unique non-RGD site near the C-terminus of human tropoelastin. Biochimie863173178
80.RodgersU. R.WeissA. S.2005Cellular interactions with elastin. Pathol Biol (Paris) 537390398
88.ShapiroS. D.EndicottS. K.et al.1991Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon. J Clin Invest87518281834
89.SmithM. J.Mc ClureM. J.et al.2008Suture-reinforced electrospun polydioxanone-elastin small-diameter tubes for use in vascular tissue engineering: a feasibility study. Acta Biomater415866
90.StarcherB.2001A ninhydrin-based assay to quantitate the total protein content of tissue samples. Anal Biochem2921125129
91.StitzelJ.LiuJ.et al.2006Controlled fabrication of a biological vascular substitute. Biomaterials27710881094
92.ThomasV.ZhangX.et al.2007Functionally graded electrospun scaffolds with tunable mechanical properties for vascular tissue regeneration. Biomed Mater24224232
93.ThomasV.ZhangX.et al.2009A biomimetic tubular scaffold with spatially designed nanofibers of protein/PDS bio-blends. Biotechnol Bioeng104510251033
94.Trabbic-CarlsonK.SettonL. A.et al.2003Swelling and mechanical behaviors of chemically cross-linked hydrogels of elastin-like polypeptides. Biomacromolecules 43572580
95.TuY.MithieuxS. M.et al.2010Synthetic elastin hydrogels that are coblended with heparin display substantial swelling, increased porosity, and improved cell penetration. J Biomed Mater Res A95412151222
96.UchimuraE.SawaY.et al.2003Novel method of preparing acellular cardiovascular grafts by decellularization with poly(ethylene glycol). J Biomed Mater Res A673834837
98.UmedaH.NakamuraF.et al.2001Oxodesmosine and isooxodesmosine, candidates of oxidative metabolic intermediates of pyridinium cross-links in elastin. Arch Biochem Biophys3851209219
99.UrbanZ.ZhangJ.et al.2001Supravalvular aortic stenosis: genetic and molecular dissection of a complex mutation in the elastin gene. Hum Genet1095512520
100.VrhovskiB.JensenS.et al.1997Coacervation characteristics of recombinant human tropoelastinEur J Biochem25019298
101.VrhovskiB.WeissA. S.1998Biochemistry of tropoelastin. Eur J Biochem2581118
102.WilliamsonM. R.ShuttleworthA.et al.2007The role of endothelial cell attachment to elastic fibre molecules in the enhancement of monolayer formation and retention, and the inhibition of smooth muscle cell recruitment. Biomaterials283553075318
103.WilsonB. D.GibsonC. C.et al.2010Novel Approach for Endothelializing Vascular Devices: Understanding and Exploiting Elastin-Endothelial Interactions. Ann Biomed Eng.
104.WiseS. G.ByromM. J.et al.2011A multilayered synthetic human elastin/polycaprolactone hybrid vascular graft with tailored mechanical properties. Acta Biomater71295303
105.WissinkM. J.van LuynM. J.et al.2000Endothelial cell seeding on crosslinked collagen: effects of crosslinking on endothelial cell proliferation and functional parameters. Thromb Haemost842325331
106.YinY.WiseS. G.et al.2009Covalent immobilisation of tropoelastin on a plasma deposited interface for enhancement of endothelialisation on metal surfaces. Biomaterials 30916751681
107.ZhangX.ThomasV.et al.2010Two ply tubular scaffolds comprised of proteins/poliglecaprone/polycaprolactone fibers. J Mater Sci Mater Med212541549
108.ZhangX.ThomasV.et al.2010An in vitro regenerated functional human endothelium on a nanofibrous electrospun scaffold. Biomaterials311543764381
109.ZhangX.XuY.et al.2011Engineering an antiplatelet adhesion layer on an electrospun scaffold using porcine endothelial progenitor cells. J Biomed Mater Res A.
110.ZouY.ZhangY.2009An experimental and theoretical study on the anisotropy of elastin network. Ann Biomed Eng37815721583
Written By
Lisa Nivison-Smith and Anthony Weiss
Submitted: 29 November 2010Published: 29 August 2011