Scaffolds for vascular constructs synthesized using hydrolyzed elastin.Abbreviations: SMC: smooth muscle cell, EC: endothelial cell, EPC: endothelial progenitor cells, Fb: fibroblast, TCPS: tissue culture polystyrene, PLGA: poly(D,L-lactide-
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.
2. Elastin formation in vivo
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.
3. The role of elastin in vivo
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).
3.2. Biological properties of elastin
Elastin plays key biological roles in the regulation of cells native to elastic tissues. Studies of elastin knockout mice reveal a crucial role for elastin in arterial morphogenesis through regulation of SMC proliferation and phenotype (Li, Brooke et al. 1998). This model is supported by
Several cell receptors have been identified for elastin (Figure 2). The most well documented of these receptors is EBP, which binds to multiple sites including the VGVAPG sequence on exon 24 of tropoelastin (Rodgers and Weiss 2005). Upon binding elastin, this receptor activates intracellular signaling pathways involved in cell proliferation, chemotaxis, migration and cell morphology for a range of cell types including SMCs, endothelial cells, fibroblasts, monocytes, leukocytes and mesenchymal cells (Senior, Griffin et al. 1980; Indik, Abrams et al. 1990; Faury, Ristori et al. 1994; Faury, Ristori et al. 1995; Kamisato, Uemura et al. 1997; Jung, Rutka et al. 1998; Mochizuki, Brassart et al. 2002). Other cell receptors, including a less documented glycoprotein termed elastonectin and G protein-coupled receptor can bind elastin through the VGVAPG sequence (Hornebeck, Tixier et al. 1986). Interactions of vascular cells with elastin via these receptors have been shown to dictate focal adhesion formation, cell proliferation and migration (Hornebeck, Tixier et al. 1986; Karnik, Brooke et al. 2003; Karnik, Wythe et al. 2003). Glycosaminoglycans on the SMC and chondrocyte cell surface dominate binding to the C-terminus of bovine tropoelastin (Broekelmann, Kozel et al. 2005; Akhtar, Broekelmann et al. 2011). Cell interactions with human tropoelastin C-terminus specifically occur through the integrin αvβ3 (Rodgers and Weiss 2004; Bax, Rodgers et al. 2009). Elastin binding for some cell types is likely to occur through multiple receptors (Bax, Rodgers et al. 2009; Wilson, Gibson et al. 2010; Akhtar, Broekelmann et al. 2011).
4. Elastin and disease
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).
5. Elastin biomaterials
Common to all elastin diseases is the catalogued
6. Decellularized tissues as elastin biomaterials
Decellularized tissues, generated by the removal of the cellular components of tissue explant are useful as biomaterials as they
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
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.
7. Tissue derived elastin constructs
7.1. Insoluble elastin materials
Elastin used for
Freeze-dried scaffolds of insoluble elastin fibers and purified collagen fibers present mechanical properties consistent with those of elastic tissues (Buttafoco, Engbers-Buijtenhuijs et al. 2006). Furthermore, these scaffolds appear to be compatible with SMCs (Buijtenhuijs, Buttafoco et al. 2004; Engbers-Buijtenhuijs, Buttafoco et al. 2005; Buttafoco, Engbers-Buijtenhuijs et al. 2006), endothelial cells (Wissink, van Luyn et al. 2000) and platelets (Koens, Faraj et al. 2010) pointing to potential vascular applications. Also, insoluble elastin/collagen scaffolds have been explored as possible dermal replacements as these materials can support fibroblasts (Daamen, van Moerkerk et al. 2003) and keratinocytes (Lammers, Tjabringa et al. 2009). Other insoluble elastin composites such as elastin/fibrin biomaterials have been generated but characterization of these materials is limited to mechanical capacity (Barbie, Angibaud et al. 1989).
7.2. Hydrolyzed elastin materials
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
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
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
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
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 | (Ito, Ishimaru et al. 1997) |
α-elastin & collagen electrospun blended conduit | -attachment & proliferation of SMCs | -no mechanical testing | (Buttafoco, Kolkman et al. 2006) |
α-elastin electrospun sheet | -SMC proliferation inhibited -α-SMA expression observed | -no mechanical testing | (Miyamoto, Atarashi et al. 2009) |
α-elastin electrospun fibers | -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 | (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 | (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 | -growth of EC, SMC and Fb in separate layers | -delamination of layers -no mechanical testing | (Boland, Matthews et al. 2004) |
α-elastin, gelatin & PDS blended electrospun conduit | -matched tensile properties & elastic modulus to femoral artery | -loss of tensile properties due to -no cell studies performed | (Thomas, Zhang et al. 2009) |
α-elastin, gelatin & Maxon multi-layered electrospun conduit | -comparable mechanical properties to femoral artery | -no cell studies performed | (Thomas, Zhang et al. 2007) |
bovine elastin, PGC, PCL & gelatin bi-layered electrospun conduit | -tensile strength matched to native artery -attachment & proliferation of EC & EPCs | -no SMC characterization | (Zhang, Thomas et al. 2010; Zhang, Thomas et al. 2010; Zhang, Xu et al. 2011) |
α-elastin, collagen, PCL tri-layered electrospun conduit | -mechanical properties matched to native artery by modulation of elastin & PCL content | -no cell studies performed | (McClure, Sell et al. 2010) |
8. Elastin-sequence based materials
8.1. Synthetic elastin-based peptides
Synthetic peptides based on key elastin sequences present elastin-like properties including self-assembly, cross-linking and cell interactions (Long, King et al. 1989; Faury, Garnier et al. 1998; Bellingham, Woodhouse et al. 2001; Karnik, Brooke et al. 2003; Karnik, Wythe et al. 2003). Coating of materials with elastin peptides can improve biocompatibility by providing protein sequences required for cell binding (reviewed by (Almine, Bax et al. 2010)). Some three dimensional materials formed from elastin-based peptides demonstrate elastin-like properties, including hydrogels that support cell growth and possess high degrees of elasticity (Keeley, Bellingham et al. 2002; Trabbic-Carlson, Setton et al. 2003). However as with hydrolyzed elastin preparations, synthetic peptides can lack the full repertoire of properties of the fully intact protein and are associated with inflammation (Faury, Ristori et al. 1995).
8.2. Recombinant human tropoelastin
Recombinant human tropoelastin (rhTE) is expressed and purified can be made as a recombinant protein in
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.
These types of synthetic elastin hydrogels can be made by chemical cross-linking (Mithieux, Rasko et al. 2004), enzyme treatment (Mithieux, Wise et al. 2005) or raising the pH (Mithieux, Tu et al. 2009) of rhTE solutions (Figure 4). The hydrogels demonstrate mechanical properties that are consistent with native elastin including low elastic moduli, support of attachment and proliferation of dermal fibroblasts (Mithieux, Rasko et al. 2004; Rnjak, Li et al. 2009; Annabi, Mithieux et al. 2010). Increases in hydrogel porosity using high pressure CO2 or the incorporation of glycosaminoglycans improve cell infiltration into hydrogels (Annabi, Mithieux et al. 2010; Tu, Mithieux et al. 2010) where the maintenance of fibroblasts within these scaffolds present them as candidate dermal substitutes.
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
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
9. Conclusion
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.
Acknowledgments
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.
Abbott W. M. Megerman J. et al. 1987 Effect of compliance mismatch on vascular graft patency.5 2 376 382 - 2.
Akhtar K. Broekelmann T. J. et al. 2011 Oxidative modifications of the C-terminal domain of tropoelastin prevent cell binding . - 3.
Almine J. F. Bax D. V. et al. 2010 Elastin-based materials.39 9 3371 3379 - 4.
Annabi N. Fathi A. et al. 2011 The effect of elastin on chondrocyte adhesion and proliferation on poly (varepsilon-caprolactone)/elastin composites. Biomaterials32 6 1517 1525 - 5.
Annabi N. Mithieux S. M. et al. 2009 Synthesis of highly porous crosslinked elastin hydrogels and their interaction with fibroblasts in vitro.30 27 4550 4557 - 6.
Annabi N. Mithieux S. M. et al. 2009 The fabrication of elastin-based hydrogels using high pressure CO(2). Biomaterials30 1 1 7 - 7.
Annabi N. Mithieux S. M. et al. 2010 Cross-linked open-pore elastic hydrogels based on tropoelastin, elastin and high pressure CO2. Biomaterials31 7 1655 1665 - 8.
Baldock C. Oberhauser A. F. et al. 2011 Shape of tropoelastin, the highly extensible protein that controls human tissue elasticity.108 11 4322 4327 - 9.
Barbie C. Angibaud C. et al. 1989 Some factors affecting properties of elastin-fibrin biomaterial. 10 7 445 448 - 10.
Bax D. V. Rodgers U. R. et al. 2009 Cell adhesion to tropoelastin is mediated via the C-terminal GRKRK motif and integrin alphaVbeta3.284 42 28616 28623 - 11.
Bellingham C. M. Woodhouse K. A. et al. 2001 Self-aggregation characteristics of recombinantly expressed human elastin polypeptides. Biochim Biophys Acta1550 1 6 19 - 12.
Boland E. D. Matthews J. A. et al. 2004 Electrospinning collagen and elastin: preliminary vascular tissue engineering.9 1422 1432 - 13.
Broekelmann T. J. Kozel B. A. et al. 2005 Tropoelastin interacts with cell-surface glycosaminoglycans via its COOH-terminal domain.280 49 40939 40947 - 14.
Brooke B. S. Bayes-Genis A. et al. 2003 New insights into elastin and vascular disease. Trends Cardiovasc Med13 5 176 181 - 15.
Buijtenhuijs P. Buttafoco L. et al. 2004 Tissue engineering of blood vessels: characterization of smooth-muscle cells for culturing on collagen-and-elastin-based scaffolds. 39(Pt 2):141 EOF 9 EOF - 16.
Buttafoco L. Engbers-Buijtenhuijs P. et al. 2006 First steps towards tissue engineering of small-diameter blood vessels: preparation of flat scaffolds of collagen and elastin by means of freeze drying.77 2 357 368 - 17.
Buttafoco L. Kolkman N. G. et al. 2006 Electrospinning of collagen and elastin for tissue engineering applications.27 5 724 734 - 18.
Callewaert B. Renard M. et al. 2011 New insights into the pathogenesis of autosomal-dominant cutis laxa with report of five ELN mutations.32 4 445 455 - 19.
Chlupac J. Filova E. et al. 2009 Blood vessel replacement: 50 years of development and tissue engineering paradigms in vascular surgery. 58 Suppl 2: S119 139 - 20.
Chuang T. H. Stabler C. et al. 2009 Polyphenol-stabilized tubular elastin scaffolds for tissue engineered vascular grafts. Tissue Eng Part A15 10 2837 2851 - 21.
Conklin B. S. Richter E. R. et al. 2002 Development and evaluation of a novel decellularized vascular xenograft.24 3 173 183 - 22.
Daamen W. F. van Moerkerk H. T. et al. 2003 Preparation and evaluation of molecularly-defined collagen-elastin-glycosaminoglycan scaffolds for tissue engineering.24 22 4001 4009 - 23.
Daamen W. F. Veerkamp J. H. et al. 2007 Elastin as a biomaterial for tissue engineering.28 30 4378 4398 - 24.
Dahl S. L. Koh J. et al. 2003 Decellularized native and engineered arterial scaffolds for transplantation.12 6 659 666 - 25.
de Chalain T. Phillips J. H. et al. 1999 Bioengineering of elastic cartilage with aggregated porcine and human auricular chondrocytes and hydrogels containing alginate, collagen, and kappa-elastin. J Biomed Mater Res44 3 280 288 - 26.
De Vries H. J. Zeegelaar J. E. et al. 1995 Reduced wound contraction and scar formation in punch biopsy wounds. Native collagen dermal substitutes. A clinical study. Br J Dermatol132 5 690 697 - 27.
Engbers-Buijtenhuijs P. Buttafoco L. et al. 2005 Analysis of the balance between proliferation and apoptosis of cultured vascular smooth muscle cells for tissue-engineering applications. 11(11-12):1631 EOF 1639 EOF - 28.
Faury G. Garnier S. et al. 1998 Action of tropoelastin and synthetic elastin sequences on vascular tone and on free Ca2+ level in human vascular endothelial cells. Circ Res82 3 328 336 - 29.
Faury G. Ristori M. T. et al. 1994 Role of the elastin-laminin receptor in the vasoregulation. C R Acad Sci III317 9 807 811 - 30.
Faury G. Ristori M. T. et al. 1995 Effect of elastin peptides on vascular tone. J Vasc Res32 2 112 119 - 31.
Gilbert T. W. Sellaro T. L. et al. 2006 Decellularization of tissues and organs. Biomaterials27 19 3675 3683 - 32.
Glagov S. Vito R. et al. 1992 Micro-architecture and composition of artery walls: relationship to location, diameter and the distribution of mechanical stress. 10(6): S101 104 - 33.
Hafemann B. Ensslen S. et al. 1999 Use of a collagen/elastin-membrane for the tissue engineering of dermis.25 5 373 384 - 34.
Han J. Lazarovici P. et al. 2011 Co-electrospun blends of PLGA, gelatin, and elastin as potential nonthrombogenic scaffolds for vascular tissue engineering.12 2 399 408 - 35.
Hinek A. 1995 The 67 kDa spliced variant of beta-galactosidase serves as a reusable protective chaperone for tropoelastin.192 185 191 discussion 191-186. - 36.
Holst J. Watson S. et al. 2010 Substrate elasticity provides mechanical signals for the expansion of hemopoietic stem and progenitor cells.28 10 1123 1128 - 37.
Hornebeck W. Tixier J. M. et al. 1986 Inducible adhesion of mesenchymal cells to elastic fibers: elastonectin. Proc Natl Acad Sci U S A83 15 5517 5520 - 38.
Hu X. Wang X. et al. 2010 Biomaterials derived from silk-tropoelastin protein systems.31 32 8121 8131 - 39.
Hucthagowder V. Morava E. et al. 2009 Loss-of-function mutations in ATP60A2 impair vesicular trafficking, tropoelastin secretion and cell survival. 18(12):2149 EOF 2165 EOF - 40.
Indik Z. Abrams W. R. et al. 1990 Production of recombinant human tropoelastin: characterization and demonstration of immunologic and chemotactic activity. Arch280 1 80 86 - 41.
Indik Z. Yeh H. et al. 1987 Alternative splicing of human elastin mRNA indicated by sequence analysis of cloned genomic and complementary DNA.84 16 5680 5684 - 42.
Ito S. Ishimaru S. et al. 1997 Inhibitory effect of type 1 collagen gel containing alpha-elastin on proliferation and migration of vascular smooth muscle and endothelial cells. 5 2 176 183 - 43.
Ito S. Ishimaru S. et al. 1998 Effect of coacervated alpha-elastin on proliferation of vascular smooth muscle and endothelial cells. Angiology49 4 289 297 - 44.
Jacob M. P. Hornebeck W. 1985 Isolation and characterisation of insoluble and kappa-elastins. L. Robert, M. Moczar and E. Moczar. Basel, Karger.4 92 129 - 45.
Jung S. Rutka J. T. et al. 1998 Tropoelastin and elastin degradation products promote proliferation of human astrocytoma cell lines.57 5 439 448 - 46.
Kagan H. M. Sullivan K. A. 1982 Lysyl oxidase: preparation and role in elastin biosynthesis. 82 Pt A:637 650 - 47.
Kamisato S. Uemura Y. et al. 1997 Involvement of intracellular cyclic GMP and cyclic GMP-dependent protein kinase in alpha-elastin-induced macrophage chemotaxis. J Biochem121 5 862 867 - 48.
Karnik S. K. Brooke B. S. et al. 2003 A critical role for elastin signaling in vascular morphogenesis and disease. Development130 2 411 423 - 49.
Karnik S. K. Wythe J. D. et al. 2003 Elastin induces myofibrillogenesis via a specific domain, VGVAPG.22 5 409 425 - 50.
Keeley F. W. Bellingham C. M. et al. 2002 Elastin 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 Sci357 1418 185 189 - 51.
Kielty C. M. 2006 Elastic fibres in health and disease.8 19 1 23 - 52.
Koens M. J. Faraj K. A. et al. 2010 Controlled fabrication of triple layered and molecularly defined collagen/elastin vascular grafts resembling the native blood vessel. Acta Biomater6 12 4666 4674 - 53.
Lammers G. Tjabringa G. S. et al. 2009 A molecularly defined array based on native fibrillar collagen for the assessment of skin tissue engineering biomaterials. Biomaterials30 31 6213 6220 - 54.
Lamprou D. Zhdan P. et al. 2010 Gelatine and Gelatine/Elastin Nanocomposites for Vascular Grafts: Processing and Characterization. J Biomater Appl. - 55.
Leach J. B. Wolinsky J. B. et al. 2005 Crosslinked alpha-elastin biomaterials: towards a processable elastin mimetic scaffold.1 2 155 164 - 56.
Lee S. J. Yoo J. J. et al. 2007 In vitro evaluation of electrospun nanofiber scaffolds for vascular graft application.83 4 999 1008 - 57.
Li D. Xia Y. N. 2004 Electrospinning of nanofibers: Reinventing the wheel?16 14 1151 1170 - 58.
Li D. Y. Brooke B. et al. 1998 Elastin is an essential determinant of arterial morphogenesis.393 6682 276 280 - 59.
Li M. Mondrinos M. J. et al. 2005 Electrospun protein fibers as matrices for tissue engineering.26 30 5999 6008 - 60.
Lloyd-Jones D. Adams R. J. et al. 2010 Heart disease and stroke statistics--2010 update: a report from the American Heart Association. 121(7): e46 e215. - 61.
Long M. M. King V. J. et al. 1989 Elastin repeat peptides as chemoattractants for bovine aortic endothelial cells.140 3 512 518 - 62.
Macchiarini P. Jungebluth P. et al. 2008 Clinical transplantation of a tissue-engineered airway. Lancet372 9655 2023 2030 - 63.
Mc Clure M. J. Sell S. A. et al. 2010 A three-layered electrospun matrix to mimic native arterial architecture using polycaprolactone, elastin, and collagen: a preliminary study. Acta Biomater6 7 2422 2433 - 64.
Mecham R. P. 1991 Elastin synthesis and fiber assembly. Ann N Y Acad Sci624 137 146 - 65.
Mithieux S. M. Rasko J. E. et al. 2004 Synthetic elastin hydrogels derived from massive elastic assemblies of self-organized human protein monomers.25 20 4921 4927 - 66.
Mithieux S. M. Tu Y. et al. 2009 In situ polymerization of tropoelastin in the absence of chemical cross-linking.30 4 431 435 - 67.
Mithieux S. M. Weiss A. S. 2005 Elastin.70 437 461 - 68.
Mithieux S. M. Wise S. G. et al. 2005 A model two-component system for studying the architecture of elastin assembly in vitro.149 3 282 289 - 69.
Miyamoto K. Atarashi M. et al. 2009 Creation of cross-linked electrospun isotypic-elastin fibers controlled cell-differentiation with new cross-linker. Int J Biol Macromol45 1 33 41 - 70.
Mochizuki S. Brassart B. et al. 2002 Signaling pathways transduced through the elastin receptor facilitate proliferation of arterial smooth muscle cells.277 47 44854 44863 - 71.
Muiznieks L. D. Jensen S. A. et al. 2003 Structural changes and facilitated association of tropoelastin. Arch Biochem Biophys410 2 317 323 - 72.
Nivison-Smith L. Rnjak J. et al. 2010 Synthetic human elastin microfibers: stable cross-linked tropoelastin and cell interactive constructs for tissue engineering applications.6 2 354 359 - 73.
Partridge S. M. Davis H. F. et al. 1955 The chemistry of connective tissues. 2. Soluble proteins derived from partial hydrolysis of elastin.61 1 11 21 - 74.
Pasquali-Ronchetti I. Baccarani-Contri M. 1997 Elastic fiber during development and aging.38 4 428 435 - 75.
Petersen T. H. Calle E. A. et al. 2010 Tissue-engineered lungs for in vivo implantation.329 5991 538 541 - 76.
Price A. P. England K. A. et al. 2010 Development of a decellularized lung bioreactor system for bioengineering the lung: the matrix reloaded. Tissue Eng Part A16 8 2581 2591 - 77.
Rnjak J. Li Z. et al. 2009 Primary human dermal fibroblast interactions with open weave three-dimensional scaffolds prepared from synthetic human elastin. Biomaterials30 32 6469 6477 - 78.
Rnjak J. Wise S. G. et al. 2011 Severe Burn Injuries and the Role of Elastin in the Design of Dermal Substitutes. . - 79.
Rodgers U. R. Weiss A. S. 2004 Integrin alpha v beta 3 binds a unique non-RGD site near the C-terminus of human tropoelastin.86 3 173 178 - 80.
Rodgers U. R. Weiss A. S. 2005 Cellular interactions with elastin. Pathol Biol (Paris)53 7 390 398 - 81.
Rosenbloom J. Abrams W. R. et al. 1993 Extracellular matrix 4: the elastic fiber. FASEB J7 13 1208 1218 - 82.
Roten S. V. Bhat S. et al. 1996 Elastic fibers in scar tissue.23 1 37 42 - 83.
Ryssel H. Gazyakan E. et al. 2008 The use of MatriDerm in early excision and simultaneous autologous skin grafting in burns--a pilot study.34 1 93 97 - 84.
Sandberg L. B. Soskel N. T. et al. 1981 Elastin structure, biosynthesis, and relation to disease states.304 10 566 579 - 85.
Schmidt C. E. Baier J. M. 2000 Acellular vascular tissues: natural biomaterials for tissue repair and tissue engineering. Biomaterials21 22 2215 2231 - 86.
Sell S. A. Mc Clure M. J. et al. 2006 Electrospun polydioxanone-elastin blends: potential for bioresorbable vascular grafts.1 2 72 80 - 87.
Senior R. M. Griffin G. L. et al. 1980 Chemotactic activity of elastin-derived peptides. J66 4 859 862 - 88.
Shapiro S. D. Endicott S. K. et al. 1991 Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon.87 5 1828 1834 - 89.
Smith M. J. Mc Clure M. J. et al. 2008 Suture-reinforced electrospun polydioxanone-elastin small-diameter tubes for use in vascular tissue engineering: a feasibility study.4 1 58 66 - 90.
Starcher B. 2001 A ninhydrin-based assay to quantitate the total protein content of tissue samples.292 1 125 129 - 91.
Stitzel J. Liu J. et al. 2006 Controlled fabrication of a biological vascular substitute.27 7 1088 1094 - 92.
Thomas V. Zhang X. et al. 2007 Functionally graded electrospun scaffolds with tunable mechanical properties for vascular tissue regeneration.2 4 224 232 - 93.
Thomas V. Zhang X. et al. 2009 A biomimetic tubular scaffold with spatially designed nanofibers of protein/PDS bio-blends.104 5 1025 1033 - 94.
Trabbic-Carlson K. Setton L. A. et al. 2003 Swelling and mechanical behaviors of chemically cross-linked hydrogels of elastin-like polypeptides. Biomacromolecules4 3 572 580 - 95.
Tu Y. Mithieux S. M. et al. 2010 Synthetic elastin hydrogels that are coblended with heparin display substantial swelling, increased porosity, and improved cell penetration.95 4 1215 1222 - 96.
Uchimura E. Sawa Y. et al. 2003 Novel method of preparing acellular cardiovascular grafts by decellularization with poly(ethylene glycol).67 3 834 837 - 97.
Biochem Soc Trans,Uitto J. Christiano A. M. Kahari V. M. Bashir M. M. Rosenbloom J. Molecular biology. pathology of. human elastin. 1991 824 829 - 98.
Umeda H. Nakamura F. et al. 2001 Oxodesmosine and isooxodesmosine, candidates of oxidative metabolic intermediates of pyridinium cross-links in elastin.385 1 209 219 - 99.
Urban Z. Zhang J. et al. 2001 Supravalvular aortic stenosis: genetic and molecular dissection of a complex mutation in the elastin gene.109 5 512 520 - 100.
Vrhovski B. Jensen S. et al. 1997 Coacervation characteristics of recombinant human tropoelastin 250 1 92 98 - 101.
Vrhovski B. Weiss A. S. 1998 Biochemistry of tropoelastin.258 1 1 18 - 102.
Williamson M. R. Shuttleworth A. et al. 2007 The 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.28 35 5307 5318 - 103.
Wilson B. D. Gibson C. C. et al. 2010 Novel Approach for Endothelializing Vascular Devices: Understanding and Exploiting Elastin-Endothelial Interactions. . - 104.
Wise S. G. Byrom M. J. et al. 2011 A multilayered synthetic human elastin/polycaprolactone hybrid vascular graft with tailored mechanical properties.7 1 295 303 - 105.
Wissink M. J. van Luyn M. J. et al. 2000 Endothelial cell seeding on crosslinked collagen: effects of crosslinking on endothelial cell proliferation and functional parameters.84 2 325 331 - 106.
Yin Y. Wise S. G. et al. 2009 Covalent immobilisation of tropoelastin on a plasma deposited interface for enhancement of endothelialisation on metal surfaces. Biomaterials30 9 1675 1681 - 107.
Zhang X. Thomas V. et al. 2010 Two ply tubular scaffolds comprised of proteins/poliglecaprone/polycaprolactone fibers.21 2 541 549 - 108.
Zhang X. Thomas V. et al. 2010 An in vitro regenerated functional human endothelium on a nanofibrous electrospun scaffold.31 15 4376 4381 - 109.
Zhang X. Xu Y. et al. 2011 Engineering an antiplatelet adhesion layer on an electrospun scaffold using porcine endothelial progenitor cells. . - 110.
Zou Y. Zhang Y. 2009 An experimental and theoretical study on the anisotropy of elastin network.37 8 1572 1583