Extracted forms of collagen are subjected to chemical cross-linking to enhance their stability. However, traditional cross-linking approaches are associated with toxicity and inflammation. This work investigates the stabilization capacity, cytotoxicity and inflammatory response of collagen scaffolds cross-linked with glutaraldehyde (GTA), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, 4-arm polyethylene glycol (PEG) succinimidyl glutarate (4SP), genipin (GEN), and oleuropein. Although all cross-linking methods reduced free amine groups, variable data were obtained with respect to denaturation temperature, resistance to collagenase digestion, and mechanical properties. With respect to biological analysis, fibroblast cultures showed no significant difference between the treatments. Although direct cultures with human-derived leukemic monocyte cells (THP-1) clearly demonstrated the cytotoxic effect of GTA, THP-1 cultures supplemented with conditioned medium from the various groups showed no significant difference between the treatments. With respect to cytokine profile, no significant difference in secretion of proinflammatory (e.g., interleukin [IL]-1β, IL-8, tumor necrosis factor-α) and anti-inflammatory (e.g., vascular endothelial growth factor) cytokines was observed between the noncross-linked and the 4SP and GEN cross-linked groups, suggesting the suitability of these agents as collagen cross-linkers.
Get full access to this article
View all access options for this article.
References
1.
FratzlP., and WeinkamerR.Nature's hierarchical materials. Prog Mater Sci, 52, 1263, 2007.
2.
FriessW.Collagen—biomaterial for drug delivery. Eur J Pharm Biopharm, 45, 113, 1998.
3.
EllingsworthL.R., DeLustroF., BrennanJ.E., SawamuraS., and McPhersonJ.The human immune response to reconstituted bovine collagen. J Immunol, 136, 877, 1986.
4.
LynnA.K., YannasI.V., and BonfieldW.Antigenicity and immunogenicity of collagen. J Biomed Mater Res B, 71, 343, 2004.
5.
LeeC.H., SinglaA., and LeeY.Biomedical applications of collagen. Int J Pharm, 221, 1, 2001.
6.
Abou NeelE.A., BozecL., KnowlesJ.C., SyedO., MuderaV., DayR., and HyunJ.K.Collagen—emerging collagen based therapies hit the patient. Adv Drug Deliv Rev, 65, 429, 2013.
7.
BrownB.N., and BadylakS.F.Expanded applications, shifting paradigms and an improved understanding of host-biomaterial interactions. Acta Biomater, 9, 4948, 2013.
8.
DelgadoL.M., BayonY., PanditA., and ZeugolisD.I.To cross-link or not to cross-link? Cross-linking associated foreign body response of collagen-based devices. Tissue Eng Part B Rev, 21, 298, 2015.
9.
LiJ., ChenJ., and KirsnerR.Pathophysiology of acute wound healing. Clin Dermatol, 25, 9, 2007.
BrownB.N., RatnerB.D., GoodmanS.B., AmarS., and BadylakS.F.Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials, 33, 3792, 2012.
12.
McDadeJ.K., Brennan-PierceE.P., AriganelloM.B., LabowR.S., and Michael LeeJ.Interactions of U937 macrophage-like cells with decellularized pericardial matrix materials: influence of crosslinking treatment. Acta Biomater, 9, 7191, 2013.
13.
GargK., PullenN.A., OskeritzianC.A., RyanJ.J., and BowlinG.L.Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds. Biomaterials, 34, 4439, 2013.
14.
ChenS., JonesJ.A., XuY., LowH.-Y., AndersonJ.M., and LeongK.W.Characterization of topographical effects on macrophage behavior in a foreign body response model. Biomaterials, 31, 3479, 2010.
15.
FranzS., AllensteinF., KajahnJ., ForstreuterI., HintzeV., MollerS., and SimonJ.C.Artificial extracellular matrices composed of collagen I and high-sulfated hyaluronan promote phenotypic and functional modulation of human pro-inflammatory M1 macrophages. Acta Biomater, 9, 5621, 2013.
16.
LucasT., WaismanA., RanjanR., RoesJ., KriegT., MullerW., RoersA., and EmingS.A.Differential roles of macrophages in diverse phases of skin repair. J Immunol, 184, 3964, 2010.
17.
MartinezF.O., and GordonS.The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep, 6, 13, 2014.
18.
McWhorterF.Y., WangT., NguyenP., ChungT., and LiuW.F.Modulation of macrophage phenotype by cell shape. Proc Natl Acad Sci U S A, 110, 17253, 2013.
19.
TabasI., and BornfeldtK.Macrophage phenotype and function in different stages of atherosclerosis. Circ Res, 118, 653, 2016.
20.
PatelU., RajasinghS., SamantaS., CaoT., DawnB., and RajasinghJ.Macrophage polarization in response to epigenetic modifiers during infection and inflammation. Drug Discov Today, 22, 186, 2017.
21.
FerranteC., and LeibovichS.Regulation of macrophage polarization and wound healing. Adv Wound Care (New Rochelle), 1, 10, 2012.
22.
OrensteinS.B., QiaoY., KluehU., KreutzerD.L., and NovitskyY.W.Activation of human mononuclear cells by porcine biologic meshes in vitro. Hernia, 14, 401, 2010.
23.
MantovaniA., SicaA., SozzaniS., AllavenaP., VecchiA., and LocatiM.The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol, 25, 677, 2004.
24.
GordonS., and TaylorP.R.Monocyte and macrophage heterogeneity. Nat Rev Immunol, 5, 953, 2005.
25.
MosserD.M., and EdwardsJ.P.Exploring the full spectrum of macrophage activation. Nat Rev Immunol, 8, 958, 2008.
26.
YahyoucheA., ZhidaoX., CzernuszkaJ.T., and CloverA.J.Macrophage-mediated degradation of crosslinked collagen scaffolds. Acta Biomater, 7, 278, 2011.
27.
HensonP.M.Mechanisms of exocytosis in phagocytic inflammatory cells. Am J Pathol, 101, 494, 1980.
28.
BrodbeckW.G., and AndersonJ.M.Giant cell formation and function. Curr Opin Hematol, 16, 53, 2009.
29.
GoughJ.E., ScotchfordC.A., and DownesS.Cytotoxicity of glutaraldehyde crosslinked collagen/poly(vinyl alcohol) films is by the mechanism of apoptosis. J Biomed Mater Res, 61, 121, 2002.
30.
HassV., Luque-MartinezI.V., GutierrezM.F., MoreiraC.G., GottiV.B., FeitosaV.P., KollerG., OtukiM.F., LoguercioA.D., and ReisA.Collagen cross-linkers on dentin bonding: Stability of the adhesive interfaces, degree of conversion of the adhesive, cytotoxicity and in situ MMP inhibition. Dent Mater, 32, 732, 2016.
31.
McGregorC., ByrneG., RahmaniB., ChisariE., KyriakopoulouK., and BurriesciG.Physical equivalency of wild type and galactose α 1,3 galactose free porcine pericardium; A new source material for bioprosthetic heart valves. Acta Biomater, 41, 204, 2016.
32.
FahrenholtzM.M., WenS., and Grande-AllenK.J.Development of a heart valve model surface for optimization of surface modifications. Acta Biomater, 26, 64, 2015.
33.
BrownB.N., LondonoR., TotteyS., ZhangL., KuklaK.A., WolfM.T., DalyK.A., ReingJ.E., and BadylakS.F.Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. Acta Biomater, 8, 978, 2012.
34.
TaguchiT., XuL., KobayashiH., TaniguchiA., KataokaK., and TanakaJ.Encapsulation of chondrocytes in injectable alkali-treated collagen gels prepared using poly(ethylene glycol)-based 4-armed star polymer. Biomaterials, 26, 1247, 2005.
ZeugolisD.I., PaulG.R., and AttenburrowG.Cross-linking of extruded collagen fibres—a biomimetic three-dimensional scaffold for tissue engineering applications. J Biomed Mater Res A, 89, 895, 2009.
37.
ZeugolisD.I., PaulR.G., and AttenburrowG.The influence of a natural cross-linking agent (Myrica rubra) on the properties of extruded collagen fibres for tissue engineering applications. Mater Sci Eng C, 30, 190, 2010.
38.
AntunesA., AttenburrowG., CovingtonA., and DingJ.Utilisation of oleuropein as a crosslinking agent in collagenic films. J Leather Sci, 2, 1, 2008.
39.
ZeugolisD., PaulR., and AttenburrowG.Factors influencing the properties of reconstituted collagen fibers prior to self-assembly: animal species and collagen extraction method. J Biomed Mater Res A, 86, 892, 2008.
40.
LareuR., ZeugolisD., Abu-RubM., PanditA., and RaghunathM.Essential modification of the Sircol Collagen Assay for the accurate quantification of collagen content in complex protein solutions. Acta Biomater, 6, 3146, 2010.
41.
ZeugolisD., LiB., LareuR., ChanC., and RaghunathM.Collagen solubility testing, a quality assurance step for reproducible electro-spun nano-fibre fabrication. A technical note. J Biomater Sci Polym Ed, 19, 1307, 2008.
42.
SatyamA., SubramanianG., RaghunathM., PanditA., and ZeugolisD.In vitro evaluation of Ficoll-enriched and genipin-stabilised collagen scaffolds. J Tissue Eng Regen Med, 8, 233, 2014.
43.
WardJ., KellyJ., WangW., ZeugolisD.I., and PanditA.Amine functionalization of collagen matrices with multifunctional polyethylene glycol systems. Biomacromolecules, 11, 3093, 2010.
44.
ZeugolisD., and RaghunathM.The physiological relevance of wet versus dry differential scanning calorimetry for biomaterial evaluation: a technical note. Polym Int, 59, 1403, 2010.
45.
HellingA., TsekouraE., BiggsM., BayonY., PanditA., and ZeugolisD.In vitro enzymatic degradation of tissue grafts and collagen biomaterials by matrix metalloproteinases: improving the collagenase assay. ACS Biomater Sci Eng (In Press); DOI: 10.1021/acsbiomaterials.5b00563.
46.
DaigneaultM., PrestonJ.A., MarriottH.M., WhyteM.K., and DockrellD.H.The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages. PLoS One, 5, e8668, 2010.
47.
HelaryC., BrowneS., MathewA., WangW., and PanditA.Transfection of macrophages by collagen hollow spheres loaded with polyplexes: a step towards modulating inflammation. Acta Biomater, 8, 4208, 2012.
48.
FullerK., GasparD., DelgadoL., PanditA., and ZeugolisD.Influence of porosity and pore shape on structural, mechanical and biological properties of poly ε-caprolactone electro-spun fibrous scaffolds. Nanomedicine (Lond), 11, 1031, 2016.
49.
ZeugolisD.I., and RaghunathM.Collagen: materials analysis and implant uses. In: DucheyneP., HealyK.E., HutmacherD.W., GraingerD.W., and KirkpatrickC.J., eds. Comprehensive Biomaterials. Oxford: Elsevier, 2011, p. 261.
50.
YeQ., HarmsenM.C., van LuynM.J., and BankR.A.The relationship between collagen scaffold cross-linking agents and neutrophils in the foreign body reaction. Biomaterials, 31, 9192, 2010.
51.
YeQ., van AmerongenM.J., SandhamJ.A., BankR.A., van LuynM.J., and HarmsenM.C.Site-specific tissue inhibitor of metalloproteinase-1 governs the matrix metalloproteinases-dependent degradation of crosslinked collagen scaffolds and is correlated with interleukin-10. J Tissue Eng Regen Med, 5, 264, 2011.
52.
BellonJ.M., RodriguezM., Gomez-GilV., SotomayorS., BujanJ., and PascualG.Postimplant intraperitoneal behavior of collagen-based meshes followed by laparoscopy. Surg Endosc, 26, 27, 2012.
53.
SundararaghavanH.G., MonteiroG.A., LapinN.A., ChabalY.J., MiksanJ.R., and ShreiberD.I.Genipin-induced changes in collagen gels: correlation of mechanical properties to fluorescence. J Biomed Mater Res A, 87, 308, 2008.
54.
FesselG., CadbyJ., WunderliS., van WeerenR., and SnedekerJ.G.Dose- and time-dependent effects of genipin crosslinking on cell viability and tissue mechanics—toward clinical application for tendon repair. Acta Biomater, 10, 1897, 2014.
55.
SanamiM., SweeneyI., ShteinZ., MeirovichS., SorushanovaA., MullenA., MiraftabM., ShoseyovO., O'DowdC., PanditA., and ZeugolisD.The influence of poly(ethylene glycol) ether tetrasuccinimidyl glutarate on the structural, physical, and biological properties of collagen fibers. J Biomed Mater Res B, 104, 914, 2016.
56.
CoteM., and DoillonC.Wettability of cross-linked collagenous biomaterials: in vitro study. Biomaterials, 13, 612, 1992.
57.
NomuraY., TokiS., IshiiY., and ShiraiK.Effect of transglutaminase on reconstruction and physicochemical properties of collagen gel from shark type I collagen. Biomacromolecules, 2, 105, 2001.
58.
SionkowskaA., and WessT.Mechanical properties of UV irradiated rat tail tendon (RTT) collagen. Intern J Biolog Macromol, 34, 9, 2004.
59.
ChristiansenD., and SilverF.Mineralization of an axially aligned collagenous matrix: a morphological study. Cells Mater, 3, 177, 1993.
60.
GroverC., GwynneJ., PughN., HamaiaS., FarndaleR., BestS., and CameronR.Crosslinking and composition influence the surface properties, mechanical stiffness and cell reactivity of collagen-based films. Acta Biomater, 8, 3080, 2012.
61.
SionkowskaA., Skopinska-WisniewskaJ., GawronM., KozlowskaJ., and PlaneckaA.Chemical and thermal cross-linking of collagen and elastin hydrolysates. Int J Biol Macromol, 47, 570, 2010.
62.
MadhavanK., BelchenkoD., MottaA., and TanW.Evaluation of composition and crosslinking effects on collagen-based composite constructs. Acta Biomater, 6, 1413, 2010.
63.
ZhangX., ChenX., YangT., ZhangN., DongL., MaS., LiuX., ZhouM., and LiB.The effects of different crossing-linking conditions of genipin on type I collagen scaffolds: an in vitro evaluation. Cell Tissue Bank, 15, 531, 2014.
64.
ScheffelD., BianchiL., SoaresD., BassoF., SabatiniC., de Souza CostaC., PashleyD., and HeblingJ.Transdentinal cytotoxicity of carbodiimide (EDC) and glutaraldehyde on odontoblast-like cells. Oper Dent, 40, 44, 2015.
65.
SalvatoreL., MadaghieleM., ParisiC., GattiF., and SanninoA.Crosslinking of micropatterned collagen-based nerve guides to modulate the expected half-life. J Biomed Mater Res A, 102, 4406, 2014.
66.
ZhuK., SlusarewiczP., and HedmanT.Thermal analysis reveals differential effects of various crosslinkers on bovine annulus fibrosis. J Orthop Res, 29, 8, 2011.
67.
LammersG., TjabringaG., SchalkwijkJ., DaamenW., and van KuppeveltT.A molecularly defined array based on native fibrillar collagen for the assessment of skin tissue engineering biomaterials. Biomaterials, 30, 6213, 2009.
68.
HaparantaA., KoivurintaJ., HamalainenE., and KellomakiM.The effect of cross-linking time on a porous freeze-dried collagen scaffold using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as a cross-linker. J Appl Biomater Biomech, 6, 89, 2008.
69.
KonnoK., HirayamaC., YasuiH., and NakamuraM.Enzymatic activation of oleuropein: a protein crosslinker used as a chemical defense in the privet tree. Proc Natl Acad Sci U S A, 96, 9159, 1999.
70.
HaughM., MurphyC., McKiernanR., AltenbuchnerC., and O'BrienF.Crosslinking and mechanical properties significantly influence cell attachment, proliferation, and migration within collagen glycosaminoglycan scaffolds. Tissue Eng Part A, 17, 1201, 2011.
71.
AwangM., FirdausM., BusraM., ChowdhuryS., FadilahN., Wan HamirulW., ReusmaazranM., AminuddinM., and RuszymahB.Cytotoxic evaluation of biomechanically improved crosslinked ovine collagen on human dermal fibroblasts. Biomed Mater Eng, 24, 1715, 2014.
72.
ChenC., MaoC., SunJ., ChenY., WangW., PanH., TangR., and GuX.Glutaraldehyde-induced remineralization improves the mechanical properties and biostability of dentin collagen. Mater Sci Eng C Mater Biol Appl, 67, 657, 2016.
73.
Perez-PuyanaV., RomeroA., and GuerreroA.Influence of collagen concentration and glutaraldehyde on collagen-based scaffold properties. J Biomed Mater Res A, 104, 1462, 2016.
74.
PowellH., and BoyceS.EDC cross-linking improves skin substitute strength and stability. Biomaterials, 27, 5821, 2006.
75.
ParkS., ParkJ., KimH., SongM., and SuhH.Characterization of porous collagen/hyaluronic acid scaffold modified by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide cross-linking. Biomaterials, 23, 1205, 2002.
76.
LeeC., GrodzinskyA., and SpectorM.The effects of cross-linking of collagen-glycosaminoglycan scaffolds on compressive stiffness, chondrocyte-mediated contraction, proliferation and biosynthesis. Biomaterials, 22, 3145, 2001.
77.
McGannM., BonitskyC., JacksonM., OvaertT., TrippelS., and WagnerD.Genipin crosslinking of cartilage enhances resistance to biochemical degradation and mechanical wear. J Orthop Res, 33, 1571, 2015.
78.
BonitskyC., McGannM., SelepM., OvaertT., TrippelS., and WagnerD.Genipin crosslinking decreases the mechanical wear and biochemical degradation of impacted cartilage in vitro. J Orthop Res, 2016 [Epub ahead of print]; DOI: 10.1002/jor.23411.
79.
AvilaM., and NaviaJ.Effect of genipin collagen crosslinking on porcine corneas. J Cataract Refract Surg, 36, 659, 2010.
80.
FesselG., WernliJ., LiY., GerberC., and SnedekerJ.Exogenous collagen cross-linking recovers tendon functional integrity in an experimental model of partial tear. J Orthop Res, 30, 973, 2012.
81.
JeongS., YoonE., LimH., SungS., and KimY.The effect of space fillers in the cross-linking processes of bioprosthesis. Biores Open Access, 2, 98, 2013.
82.
EneaD., HensonF., KewS., WardaleJ., GetgoodA., BrooksR., and RushtonN.Extruded collagen fibres for tissue engineering applications: effect of crosslinking method on mechanical and biological properties. J Mater Sci Mater Med, 22, 1569, 2011.
83.
FratzlP., MisofK., ZizakI., RappG., AmenitschH., and BernstorffS.Fibrillar structure and mechanical properties of collagen. J Struct Biol, 122, 119, 1998.
84.
PurslowP., WessT., and HukinsD.Collagen orientation and molecular spacing during creep and stress-relaxation in soft connective tissues. J Exp Biol, 201, 135, 1998.
85.
RigbyB., HiraiN., SpikesJ., and EyringH.The mechanical properties of rat tail tendon. J Gen Physiol, 43, 265, 1959.
86.
SaitoH., MurabayashiS., MitamuraY., and TaguchiT.Characterization of alkali-treated collagen gels prepared by different crosslinkers. J Mater Sci Mater Med, 19, 1297, 2008.
87.
WissinkM., van LuynM., BeerninkR., DijkF., PootA., EngbersG., BeugelingT., van AkenW., and FeijenJ.Endothelial cell seeding on crosslinked collagen: effects of crosslinking on endothelial cell proliferation and functional parameters. Thromb Haemost, 84, 325, 2000.
88.
XingS., WaddellJ., and BoyntonE.Changes in macrophage morphology and prolonged cell viability following exposure to polyethylene particulate in vitro. Microsc Res Tech, 57, 523, 2002.
89.
BuchacherT., Ohradanova-RepicA., StockingerH., FischerM., and WeberV.M2 polarization of human macrophages favors survival of the intracellular pathogen Chlamydia pneumoniae. PLoS One, 10, e0143593, 2015.
90.
FéréolS., FodilR., LabatB., GaliacyS., LaurentV.M., LouisB., IsabeyD., and PlanusE.Sensitivity of alveolar macrophages to substrate mechanical and adhesive properties. Cell Motil Cytoskeleton, 63, 321, 2006.
91.
SridharanR., CameronA.R., KellyD.J., KearneyC.J., and O'BrienF.J.Biomaterial based modulation of macrophage polarization: a review and suggested design principles. Mater Today, 18, 313, 2015.
BlakneyA., SwartzlanderM., and BryantS.The effects of substrate stiffness on the in vitro activation of macrophages and in vivo host response to poly(ethylene glycol)-based hydrogels. J Biomed Mater Res A, 100, 1375, 2012.
94.
ChristoS., BachhukaA., DienerK., MierczynskaA., HayballJ., and VasilevK.The role of surface nanotopography and chemistry on primary neutrophil and macrophage cellular responses. Adv Healthc Mater, 5, 956, 2016.
95.
RefaiA., TextorM., BrunetteD., and WaterfieldJ.Effect of titanium surface topography on macrophage activation and secretion of proinflammatory cytokines and chemokines. J Biomed Mater Res A, 70, 194, 2004.
96.
ChristoS., BachhukaA., DienerK., VasilevK., and HayballJ.The contribution of inflammasome components on macrophage response to surface nanotopography and chemistry. Sci Rep, 6, 26207, 2016.
97.
LimJ., and DonahueH.Cell sensing and response to micro- and nanostructured surfaces produced by chemical and topographic patterning. Tissue Eng, 13, 1879, 2007.
98.
BayrakA., TyrallaM., LadhoffJ., SchleicherM., StockU.A., VolkH.D., and SeifertM.Human immune responses to porcine xenogeneic matrices and their extracellular matrix constituents in vitro. Biomaterials, 31, 3793, 2010.
99.
UmashankarP.R., MohananP.V., and KumariT.V.Glutaraldehyde treatment elicits toxic response compared to decellularization in bovine pericardium. Toxicol Int, 19, 51, 2012.
100.
HeyK.B., LachsC.M., RaxworthyM.J., and WoodE.J.Crosslinked fibrous collagen for use as a dermal implant: control of the cytotoxic effects of glutaraldehyde and dimethylsuberimidate. Biotechnol Appl Biochem, 12, 85, 1990.
101.
ChapmanJ.A., TzaphlidouM., MeekK.M., and KadlerK.E.The collagen fibril—a model system for studying the staining and fixation of a protein. Electron Microsc Rev, 3, 143, 1990.
102.
LeeC.R., GrodzinskyA.J., and SpectorM.The effects of cross-linking of collagen-glycosaminoglycan scaffolds on compressive stiffness, chondrocyte-mediated contraction, proliferation and biosynthesis. Biomaterials, 22, 3145, 2001.
103.
LevyR.J., SchoenF.J., ShermanF.S., NicholsJ., HawleyM.A., and LundS.A.Calcification of subcutaneously implanted type I collagen sponges. Effects of formaldehyde and glutaraldehyde pretreatments. Am J Pathol, 122, 71, 1986.
104.
McPhersonJ.M., SawamuraS., and ArmstrongR.An examination of the biologic response to injectable, glutaraldehyde cross-linked collagen implants. J Biomed Mater Res, 20, 93, 1986.
105.
LiangH.C., ChangY., HsuC.K., LeeM.H., and SungH.W.Effects of crosslinking degree of an acellular biological tissue on its tissue regeneration pattern. Biomaterials, 25, 3541, 2004.
106.
GinerE., AndujarI., RecioM.C., RiosJ.L., Cerda-NicolasJ.M., and GinerR.M.Oleuropein ameliorates acute colitis in mice. J Agric Food Chem, 59, 12882, 2011.
107.
KontturiL., JärvinenE., MuhonenV., CollinE., PanditA., KivirantaI., YliperttulaM., and UrttiA.An injectable, in situ forming type II collagen/hyaluronic acid hydrogel vehicle for chondrocyte delivery in cartilage tissue engineering. Drug Deliv Transl Res, 4, 149, 2014.
108.
KatoM., TaguchiT., and KobayashiH.An attempt to construct the stroma of cornea using primary cultured corneal cells. J Nanosci Nanotechnol, 7, 748, 2007.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
