Skip to main content
SpringerLink
Log in

Biaxial mechanical properties of bovine jugular venous valve leaflet tissues

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

Venous valve incompetence has been implicated in diseases ranging from chronic venous insufficiency (CVI) to intracranial venous hypertension. However, while the mechanical properties of venous valve leaflet tissues are central to CVI biomechanics and mechanobiology, neither stress–strain curves nor tangent moduli have been reported. Here, equibiaxial tensile mechanical tests were conducted to assess the tangent modulus, strength and anisotropy of venous valve leaflet tissues from bovine jugular veins. Valvular tissues were stretched to 60% strain in both the circumferential and radial directions, and leaflet tissue stress–strain curves were generated for proximal and distal valves (i.e., valves closest and furthest from the right heart, respectively). Toward linking mechanical properties to leaflet microstructure and composition, Masson’s trichrome and Verhoeff–Van Gieson staining and collagen assays were conducted. Results showed: (1) Proximal bovine jugular vein venous valves tended to be bicuspid (i.e., have two leaflets), while distal valves tended to be tricuspid; (2) leaflet tissues from proximal valves exhibited approximately threefold higher peak tangent moduli in the circumferential direction than in the orthogonal radial direction (i.e., proximal valve leaflet tissues were anisotropic; \(p<0.01\)); (3) individual leaflets excised from the same valve apparatus appeared to exhibit different mechanical properties (i.e., intra-valve variability); and (4) leaflets from distal valves exhibited a trend of higher soluble collagen concentrations than proximal ones (i.e., inter-valve variability). To the best of the authors’ knowledge, this is the first study reporting biaxial mechanical properties of venous valve leaflet tissues. These results provide a baseline for studying venous valve incompetence at the tissue level and a quantitative basis for prosthetic venous valve design.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ackroyd JS, Pattison M, Browse NL (1985) A study of the mechanical properties of fresh and preserved human femoral vein wall and valve cusps. Br J Surg 72:117–119

    Article  Google Scholar 

  • Aldous IG, Veres SP, Jahangir A, Lee JM (2009) Differences in collagen cross-linking between the four valves of the bovine heart: a possible role in adaptation to mechanical fatigue. Am J Physiol Heart Circ Physiol 296:H1898–1906. doi:10.1152/ajpheart.01173.2008

    Article  Google Scholar 

  • Bazigou E, Lyons OT, Smith A, Venn GE, Cope C, Brown NA, Makinen T (2011) Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice. J Clin Investig 121:2984–2992. doi:10.1172/JCI58050

    Article  Google Scholar 

  • Bazigou E, Makinen T (2013) Flow control in our vessels: vascular valves make sure there is no way back. Cell Mol Life Sci 70:1055–1066. doi:10.1007/s00018-012-1110-6

    Article  Google Scholar 

  • Beebe-Dimmer JL, Pfeifer JR, Engle JS, Schottenfeld D (2005) The epidemiology of chronic venous insufficiency and varicose veins. Ann Epidemiol 15:175–184. doi:10.1016/j.annepidem.2004.05.015

    Article  Google Scholar 

  • Bergan JJ (2008) Venous valve incompetence: the first culprit in the pathophysiology of chronic venous insufficiency. Medicographia 30:87–94

    Google Scholar 

  • Bernardini E, De Rango P, Piccioli R, Bisacci C, Pagliuca V, Genovese G, Bisacci R (2010) Development of primary superficial venous insufficiency: the ascending theory. Observational and hemodynamic data from a 9-year experience. Ann Vasc Surg 24:709–720. doi:10.1016/j.avsg.2010.01.011

    Article  Google Scholar 

  • Billiar KL, Sacks MS (2000) Biaxial mechanical properties of the natural and glutaraldehyde treated aortic valve cusp—part I: experimental results. J Biomech Eng 122:23–30

    Article  Google Scholar 

  • Brountzos E et al (2003) Remodeling of suspended small intestinal submucosa venous valve: an experimental study in sheep to assess the host cells’ origin. J Vasc Interv Radiol 14:349–356. doi:10.1097/01.Rvi.0000058410.01661.62

    Article  Google Scholar 

  • Buchanan RM, Sacks MS (2013) Interlayer micromechanics of the aortic heart valve leaflet. Biomech Model Mechanobiol. doi:10.1007/s10237-013-0536-6

    Google Scholar 

  • Buchtemann AS, Steins A, Volkert B, Hahn M, Klyscz T, Junger M (1999) The effect of compression therapy on venous haemodynamics in pregnant women. Br J Obstetri Gynaecol 106:563–569

    Article  Google Scholar 

  • Buescher CD, Nachiappan B, Brumbaugh JM, Hoo KA, Janssen HF (2005) Experimental studies of the effects of abnormal venous valves on fluid flow. Biotechnol Prog 21:938–945. doi:10.1021/bp049835u

    Article  Google Scholar 

  • Buxton GA, Clarke N (2006) Computational phlebology: the simulation of a vein valve. J Biol Phys 32:507–521. doi:10.1007/s10867-007-9033-4

    Article  Google Scholar 

  • Carrel T (2004) Bovine valved jugular vein (Contegra\(^{{\rm TM}}\)) to reconstruct the right ventricular outflow tract. Expert Rev Med Devices 1:11–19. doi:10.1586/17434440.1.1.11

    Article  Google Scholar 

  • Chauveau M, Gelade P, Cros F (2011) The venous return simulator: comparison of simulated with measured ambulatory venous pressure in normal subjects and in venous valve incompetence. VASA Z Gefasskrankh 40:205–217. doi:10.1024/0301-1526/a000095

    Article  Google Scholar 

  • Chen HY, Berwick Z, Krieger J, Chambers S, Lurie F, Kassab GS (2014) Biomechanical comparison between mono-, bi-, and tricuspid valve architectures. J Vasc Surg Venous Lymphat Disord 2:188–193. doi:10.1016/j.jvsv.2013.08.004

    Article  Google Scholar 

  • Corno AF, Hurni M, Griffin H, Jeanrenaud X, von Segesser LK (2001) Glutaraldehyde-fixed bovine jugular vein as a substitute for the pulmonary valve in the Ross operation. J Thorac Cardiovasc Surg 122:493–494. doi:10.1067/mtc.2001.114780

    Article  Google Scholar 

  • Davis FM, De Vita R (2012) A nonlinear constitutive model for stress relaxation in ligaments and tendons. Ann Biomed Eng 40:2541–2550. doi:10.1007/s10439-012-0596-2

    Article  Google Scholar 

  • de Borst GJ, Moll FL (2012) Percutaneous venous valve designs for treatment of deep venous insufficiency. J Endovasc Ther 19:291–302. doi:10.1583/11-3766R.1

    Article  Google Scholar 

  • de Borst GJ, Teijink JA, Patterson M, Quijano TC, Moll FL (2003) A percutaneous approach to deep venous valve insufficiency with a new self-expanding venous frame valve. J Endovasc Ther 10:341–349. doi:10.1177/152660280301000227

    Google Scholar 

  • DeLaria GA, Phifer T, Roy J, Tu R, Thyagarajan K, Quijano RC (1993) Hemodynamic evaluation of a bioprosthetic venous prosthesis. J Vasc Surg 18:577–584 (discussion 584-576)

    Article  Google Scholar 

  • Edwards JE, Edwards EA (1940) The saphenous valves in varicose veins. Am Heart J 19:338

    Article  Google Scholar 

  • Engelmayr GC Jr, Rabkin E, Sutherland FW, Schoen FJ, MJ E Jr, Sacks MS (2005) The independent role of cyclic flexure in the early in vitro development of an engineered heart valve tissue. Biomaterials 26:175–187

    Article  Google Scholar 

  • Fan CM (2005) Venous pathophysiology. Semin Intervent Radiol 22:157–161. doi:10.1055/s-2005-921949

    Article  Google Scholar 

  • Franklin K (1927) Valves in veins: an historical survey. Proc R Soc Med 21:1–33

    Google Scholar 

  • Franklin K (1929) Valves in veins: further observations. J Anat 64:67–69

    Google Scholar 

  • Glynn JJ, Jones CM, Anderson DEJ, Pavcnik D, Hinds MT (2016) In vivo assessment of two endothelialization approaches on bioprosthetic valves for the treatment of chronic deep venous insufficiency. J Biomed Mater Res B 104:1610–1621. doi:10.1002/jbm.b.33507

    Article  Google Scholar 

  • Gottlob R, May R (1986) Venous valves: morphology, function, radiology, surgery. Springer-Verlag, Wien, New York

    Book  Google Scholar 

  • Hilbert SL, Sword LC, Batchelder KF, Barrick MK, Ferrans VJ (1996) Simultaneous assessment of bioprosthetic heart valve biomechanical properties and collagen crimp length. J Biomed Mater Res 31:503–509. doi:10.1002/(Sici)1097-4636(199608)31:4<503::Aid-Jbm10>3.0.Co;2-H

  • Hill R, Schmidt S, Evancho M, Hunter T, Hillegass D, Sharp W (1985) Development of a prosthetic venous valve. J Biomed Mater Res 19:827–832. doi:10.1002/jbm.820190708

    Article  Google Scholar 

  • Huang H-YS, Balhouse BN, Huang S (2012) Application of simple biomechanical and biochemical tests to heart valve leaflets: implications for heart valve characterization and tissue engineering. Proc Inst Mech Eng Part H 226:868–876. doi:10.1177/0954411912455004

    Article  Google Scholar 

  • Huang H-YS, Huang S, Frazier CP, Prim P, Harrysson O (2014) Directional mechanical property of porcine skin tissues. J Mech Med Biol. doi:10.1142/S0219519414500699

    Google Scholar 

  • Huang H-YS, Liao J, Sacks MS (2007) In-situ deformation of the aortic valve interstitial cell nucleus under diastolic loading. J Biomech Eng Trans ASME 129:880–889. doi:10.1115/1.2801670

    Article  Google Scholar 

  • Huang S, Huang H-YS (2015) Biaxial stress relaxation of semilunar heart valve leaflets during simulated collagen catabolism: effects of collagenase concentration and equibiaxial strain-state. Proc Inst Mech Eng Part H 229:721–731. doi:10.1177/0954411915604336

    Article  Google Scholar 

  • James KV, Lohr JM, Deshmukh RM, Cranley JJ (1996) Venous thrombotic complications of pregnancy. Cardiovasc Surg 4:777–782

    Article  Google Scholar 

  • Jones CM, Hinds MT, Pavcnik D (2012) Retention of an autologous endothelial layer on a bioprosthetic valve for the treatment of chronic deep venous insufficiency. J Vasc Interv Radiol 23:697–703. doi:10.1016/j.jvir.2012.01.062

    Article  Google Scholar 

  • Kampmeier OF, Birch CLF (1927) The origin and development of the venous valves, with particular reference to the saphenous district. Am J Anat 38:451–499. doi:10.1002/aja.1000380306

    Article  Google Scholar 

  • Karino T, Motomiya M (1984) Flow through a venous valve and its implication for thrombus formation. Thrombosis Res 36:245–257

    Article  Google Scholar 

  • Kehl D, Weber B, Hoerstrup SP (2016) Bioengineered living cardiac and venous valve replacements: current status and future prospects. Cardiovasc Pathol 25:300–305. doi:10.1016/j.carpath.2016.03.001

    Article  Google Scholar 

  • Kistner RL (1968) Surgical repair of a venous valve. Straub Clin Proc 34:41–43

    Google Scholar 

  • Kuna VK et al (2015) Successful tissue engineering of competent allogeneic venous valves. J Vasc Surg Venous Lymphat Disord 3:421–430. doi:10.1016/j.jvsv.2014.12.002

    Article  Google Scholar 

  • Liao J, Joyce EM, Sacks MS (2008) Effects of decellularization on the mechanical and structural properties of the porcine aortic valve leaflet. Biomaterials 29:1065–1074. doi:10.1016/j.biomaterials.2007.11.007

    Article  Google Scholar 

  • Lochner P, Nedelmann M, Kaps M, Stolz E (2014) Jugular valve incompetence in transient global amnesia. A problem revisited. J Neuroimaging 24:479–483. doi:10.1111/jon.12042

    Article  Google Scholar 

  • Lurie F, Kistner RL, Eklof B, Kessler D (2003) Mechanism of venous valve closure and role of the valve in circulation: a new concept. J Vasc Surg 38:955–961. doi:10.1016/S0741

    Article  Google Scholar 

  • Masoumi N, Jean A, Zugates JT, Johnson KL, Engelmayr GC (2013) Laser microfabricated poly (glycerol sebacate) scaffolds for heart valve tissue engineering. J Biomed Mater Res Part A 101:104–114. doi:10.1002/Jbm.A.34305

    Article  Google Scholar 

  • Masoumi N, Johnson KL, Howell MC, Engelmayr GC Jr (2013) Valvular interstitial cell seeded poly (glycerol sebacate) scaffolds: toward a biomimetic in vitro model for heart valve tissue engineering. Acta Biomater 9:5974–5988. doi:10.1016/j.actbio.2013.01.001

    Article  Google Scholar 

  • May-Newman K, Lam C, Yin FCP (2009) A hyperelastic constitutive law for aortic valve tissue. J Biomech Eng. doi:10.1115/1.3127261

    Google Scholar 

  • McElhinney DB, Hennesen JT (2013) The Melody\(\textregistered \) valve and Ensemble\(\textregistered \) delivery system for transcatheter pulmonary valve replacement. Ann NY Acad Sci 1291:77–85. doi:10.1111/nyas.12194

    Article  Google Scholar 

  • Moore HM, Gohel M, Davies AH (2011) Number and location of venous valves within the popliteal and femoral veins: a review of the literature. J Anat 219:439–443. doi:10.1111/j.1469-7580.2011.01409.x

  • Moriyama M, Kubota S, Tashiro H, Tonami H (2011) Evaluation of prosthetic venous valves, fabricated by electrospinning, for percutaneous treatment of chronic venous insufficiency. J Artif Organs 14:294–300. doi:10.1007/s10047-011-0588-2

    Article  Google Scholar 

  • Munger SJ, Geng X, Srinivasan RS, Witte MH, Paul DL, Simon AM (2016) Segregated Foxc2, NFATc1 and Connexin expression at normal developing venous valves, and Connexin-specific differences in the valve phenotypes of Cx37, Cx43, and Cx47 knockout mice. Dev Biol 412:173–190. doi:10.1016/j.ydbio.2016.02.033

    Article  Google Scholar 

  • Munger SJ, Kanady JD, Simon AM (2013) Absence of venous valves in mice lacking Connexin37. Dev Biol 373:338–348. doi:10.1016/j.ydbio.2012.10.032

    Article  Google Scholar 

  • Narracott AJ, Zervides C, Diaz V, Rafiroiu D, Lawford PV, Hose DR (2010) Analysis of a mechanical heart valve prosthesis and a native venous valve: two distinct applications of FSI to biomedical applications. Int J Numer Methods Biomed Eng 26:421–434

    Article  MATH  Google Scholar 

  • Nedelmann M, Kaps M, Mueller-Forell W (2009) Venous obstruction and jugular valve insufficiency in idiopathic intracranial hypertension. J Neurol 256:964–969. doi:10.1007/s00415-009-5056-z

    Article  Google Scholar 

  • Noishiki Y et al (1993) Development and evaluation of a pliable biological valved conduit. 1. Preparation, biochemical-properties, and histological-findings. Int J Artif Organs 16:192–198

    Google Scholar 

  • Padberg FT Jr, Johnston MV, Sisto SA (2004) Structured exercise improves calf muscle pump function in chronic venous insufficiency: a randomized trial. J Vasc Surg 39:79–87. doi:10.1016/j.jvs.2003.09.036

    Article  Google Scholar 

  • Pavcnik D, Uchida BT, Timmermans H, Corless CL, Keller FS, Rosch J (2000) Aortic and venous valve for percutaneous insertion. Minim Invasive Ther Allied Technol 9:287–292. doi:10.1080/13645700009169659

    Article  Google Scholar 

  • Pavcnik D et al (2002) Percutaneous bioprosthetic venous valve: a long-term study in sheep. J Vasc Surg 35:598–602. doi:10.1067/mva.2002.118825

    Article  Google Scholar 

  • Qui Y, Quijano RC, Wang SK, Hwang NH (1995) Fluid dynamics of venous valve closure. Ann Biomed Eng 23:750–759

    Article  Google Scholar 

  • Qureshi MI et al (2015) A study to evaluate patterns of superficial venous reflux in patients with primary chronic venous disease. Phlebology 30:455–461. doi:10.1177/0268355514536384

    Article  Google Scholar 

  • Reeves TR, Cezeaux JL, Sackman JE, Cassada DC, Freeman MB, Stevens SL, Goldman MH (1997) Mechanical characteristics of lyophilized human saphenous vein valves. J Vasc Surg 26:823–828

    Article  Google Scholar 

  • Rittgers SE, Oberdier MT, Pottala S (2007) Physiologically-based testing system for the mechanical characterization of prosthetic vein valves. Biomed Eng Online 6:29. doi:10.1186/1475-925X-6-29

    Article  Google Scholar 

  • Sabine A et al (2012) Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. Dev Cell 22:430–445. doi:10.1016/j.devcel.2011.12.020

  • Shen MR et al (2014) Biocompatibility evaluation of tissue-engineered valved venous conduit by reseeding autologous bone marrow-derived endothelial progenitor cells and multipotent adult progenitor cells into heterogeneous decellularized venous matrix. J Tissue Eng Regen Med. doi:10.1002/term.1877

    Google Scholar 

  • Sparey C, Haddad N, Sissons G, Rosser S, de Cossart L (1999) The effect of pregnancy on the lower-limb venous system of women with varicose veins. Eur J Vasc Endovasc Surg 18:294–299. doi:10.1053/ejvs.1999.0870

    Article  Google Scholar 

  • Stella JA, Liao J, Sacks MS (2007) Time-dependent biaxial mechanical behavior of the aortic heart valve leaflet. J Biomech 40:3169–3177. doi:10.1016/j.jbiomech.2007.04.001

    Article  Google Scholar 

  • Sun W, Sacks M, Fulchiero G, Lovekamp J, Vyavahare N, Scott M (2004) Response of heterograft heart valve biomaterials to moderate cyclic loading. J Biomed Mater Res A 69:658–669. doi:10.1002/jbm.a.30031

    Article  Google Scholar 

  • Teebken OE, Puschmann C, Aper T, Haverich A, Mertsching H (2003) Tissue-engineered bioprosthetic venous valve: a long-term study in sheep. Eur J Vasc Endovasc Surg 25:305–312. doi:10.1053/ejvs.2002.1873

    Article  Google Scholar 

  • Teebken OE, Puschmann C, Breitenbach I, Rohde B, Burgwitz K, Haverich A (2009) Preclinical development of tissue-engineered vein valves and venous substitutes using re-endothelialised human vein matrix. Eur J Vasc Endovasc Surg 37:92–102. doi:10.1016/j.ejvs.2008.10.012

    Article  Google Scholar 

  • Tripathi R, Sieunarine K, Abbas M, Durrani N (2004) Deep venous valve reconstruction for non-healing leg ulcers: techniques and results. ANZ J Surg 74:34–39

    Article  Google Scholar 

  • Tseng H, Grande-Allen KJ (2011) Elastic fibers in the aortic valve spongiosa: a fresh perspective on its structure and role in overall tissue function. Acta Biomater 7:2101–2108. doi:10.1016/j.actbio.2011.01.022

    Article  Google Scholar 

  • van Geemen D, Driessen-Mol A, Grootzwagers LGM, Soekhradj-Soechit RS, Vis PWR, Baaijens FPT, Bouten CVC (2012) Variation in tissue outcome of ovine and human engineered heart valve constructs: relevance for tissue engineering. Regen Med 7:59–70. doi:10.2217/rme.11.100

    Article  Google Scholar 

  • Vogel D, Walsh ME, Chen JT, Comerota AJ (2012) Comparison of vein valve function following pharmacomechanical thrombolysis versus simple catheter-directed thrombolysis for iliofemoral deep vein thrombosis. J Vasc Surg 56:1351–1354. doi:10.1016/j.jvs.2012.02.053

    Article  Google Scholar 

  • Weber B et al (2014) Living-engineered valves for transcatheter venous valve repair. Tissue Eng Part C Methods. doi:10.1089/ten.TEC.2013.0187

    Google Scholar 

  • Wen Y et al (2012) Construction of tissue-engineered venous valves in vitro using two types of progenitor cells and decellularized scaffolds category: original article. Open Tissue Eng Regen Med J 5:9–16. doi:10.2174/1875043501205010009

    Article  Google Scholar 

  • Yuan JM et al (2013) Functional analysis in vivo of engineered valved venous conduit with decellularized matrix and two bone marrow-derived progenitors in sheep. J Tissue Eng Regen Med. doi:10.1002/term.1748

    Google Scholar 

  • Zervides C, Giannoukas AD (2012) Historical overview of venous valve prostheses for the treatment of deep venous valve insufficiency. J Endovasc Ther 19:281–290. doi:10.1583/11-3594MR.1

    Article  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge Mr. George C. Engelmayr, Sr., for his assistance in sourcing bovine jugular vein tissues and Adam Benson for performing collagen assays on lyophilized valve tissues. This work was supported by NSF CBET-1553430.

Author information

Authors and Affiliations

  1. Department of Mechanical and Aerospace Engineering, North Carolina State University, R3158 Engineering Building 3, Campus Box 7910, 911 Oval Drive, Raleigh, NC, 27695, USA

    Hsiao-Ying Shadow Huang & Jiaqi Lu

Authors
  1. Hsiao-Ying Shadow Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiaqi Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hsiao-Ying Shadow Huang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, HY.S., Lu, J. Biaxial mechanical properties of bovine jugular venous valve leaflet tissues. Biomech Model Mechanobiol 16, 1911–1923 (2017). https://doi.org/10.1007/s10237-017-0927-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-017-0927-1

Keywords

Search

Navigation