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Mechanical characterization of fibrotic and mineralized tissue in Peyronie’s disease

Abstract

Peyronie’s disease affects penile mechanics, but published research lacks biomechanical characterization of affected tunica albuginea. This work aims to establish mechanical testing methodology and characterize pathological tissue mechanics of Peyronie’s disease. Tunica albuginea was obtained from patients (n = 5) undergoing reconstructive surgery for Peyronie’s disease, sectioned into test specimens (n = 12), stored frozen at −20 °C, and imaged with micro-computed tomography (µCT). A tensile testing protocol was developed based on similar soft tissues. Correlation of mechanical summary variables (force, displacement, stiffness, work, Young’s modulus, ultimate tensile stress, strain at ultimate tensile stress, and toughness) and µCT features were assessed with linear regression. Specimens empirically grouped into hard or soft stress–strain behavior were compared using a Student’s t-test. Surface strain and failure patterns were described qualitatively. Specimens displayed high inter- and intra-subject variability. Mineralization volume was not correlated with mechanical parameters. Empirically hard tissue had higher ultimate tensile stress. Failure mechanisms and strain patterns differed between mineralized and non-mineralized specimens. Size, shape, and quantity of mineralization may be more important in determining Peyronie’s disease plaque behavior than presence of mineralization alone, and single summary variables like modulus may not fully describe mechanical behavior.

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Fig. 1: Proposed mechanical testing protocol.
Fig. 2: Pilot data.
Fig. 3: Two-dimensional projections of µCT scans.
Fig. 4: Regression of geometric and material variables.
Fig. 5: Representative soft tissue failure, specimen E3.
Fig. 6: Representative hard tissue failure, specimen C2.

References

  1. 1.

    Dibenedetti DB, Nguyen D, Zografos L, Ziemiecki R, Zhou X. A population-based study of peyronie’s disease: prevalence and treatment patterns in the United States. Adv Urol. 2011;2011:1–9. http://www.ncbi.nlm.nih.gov/pubmed/22110491.

  2. 2.

    ten Dam E-JPM, van Driel MF, de Jong IJ, Werker PMN, Bank RA. Glimpses into the molecular pathogenesis of Peyronie’s disease. Aging Male. 2019;1–9. https://www.tandfonline.com/doi/full/10.1080/13685538.2019.1643311.

  3. 3.

    Patel DP, Christensen MB, Hotaling JM, Pastuszak AW. A review of inflammation and fibrosis: implications for the pathogenesis of Peyronie’s disease. World J Urol. 2020:38;253–61. http://link.springer.com/10.1007/s00345-019-02815-6.

  4. 4.

    Bitsch M, Kromann-Andersen B, Schou J, Sjøntoft E. The elasticity and the tensile strength of Tunica Albuginea of the Corpora Cavernosa. J Urol. 1990;143:642–5. https://www.sciencedirect.com/science/article/abs/pii/S0022534717400474.

  5. 5.

    Hsu GL, Brock G, Martinez-Pineiro L, Von Heyden B, Lue TF, Tanagho EA. Anatomy and strength of the tunica albuginea: its relevance to penile prosthesis extrusion. J Urol. 1994;151:1205–8. https://www.sciencedirect.com/science/article/abs/pii/S002253471735214X.

  6. 6.

    Inci E, Turkay R, Nalbant MO, Yenice MG, Tugcu V. The value of shear wave elastography in the quantification of corpus cavernosum penis rigidity and its alteration with age. Eur J Radiol. 2017;89:106–10. https://www.sciencedirect.com/science/article/abs/pii/S0720048X17300335.

  7. 7.

    Richards G, Goldenberg E, Pek H, Gilbert BR. Penile sonoelastography for the localization of a non-palpable, non-sonographically visualized lesion in a patient with penile curvature from peyronie’s disease. J Sex Med. 2014;11:516–20. https://linkinghub.elsevier.com/retrieve/pii/S1743609515306834.

  8. 8.

    Trama F, Riccardo F, Ruffo A, Celentano G, Romeo G, Russo A. Elastosonographic changes in patients with Peyronie’s disease, before and after treatment with a compound based on Ecklonia bicyclis, Tribulus terrestris, and water-soluble Chitosan. Open J Urol. 2018;08:77–87. http://www.scirp.org/journal/doi.aspx?DOI=10.4236/oju.2018.83009.

  9. 9.

    Walraevens J, Willaert B, De Win G, Ranftl A, De Schutter J, Sloten JV. Correlation between compression, tensile and tearing tests on healthy and calcified aortic tissues. Med Eng Phys. 2008;30:1098–104. http://www.ncbi.nlm.nih.gov/pubmed/18342563.

  10. 10.

    Holzapfel GA, Sommer G, Regitnig P. Anisotropic mechanical properties of tissue components in human atherosclerotic plaques. J Biomech Eng. 2004;126:657–65. https://asmedigitalcollection.asme.org/biomechanical/article/126/5/657/445262/Anisotropic-Mechanical-Properties-of-Tissue.

  11. 11.

    Sherebrin MH, Bernans HA, Roach MR. Extensibility changes of calcified soft tissue strips from human aorta. Can J Physiol Pharmacol. 1987;65:1878–83. http://www.ncbi.nlm.nih.gov/pubmed/3690406.

  12. 12.

    Loree HM, Grodzinsky AJ, Park SY, Gibson LJ, Lee RT. Static circumferential tangential modulus of human atherosclerotic tissue. J Biomech. 1994;27:195–204. http://www.ncbi.nlm.nih.gov/pubmed/8132688.

  13. 13.

    Maher E, Creane A, Sultan S, Hynes N, Lally C, Kelly DJ. Tensile and compressive properties of fresh human carotid atherosclerotic plaques. J Biomech. 2009;42:2760–7. http://www.ncbi.nlm.nih.gov/pubmed/19766226.

  14. 14.

    Barrett HE, Cunnane EM, Kavanagh EG, Walsh MT. On the effect of calcification volume and configuration on the mechanical behaviour of carotid plaque tissue. J Mech Behav Biomed Mater. 2016;56:45–56. http://www.ncbi.nlm.nih.gov/pubmed/26655460.

  15. 15.

    Yurkanin JP, Dean R, Wessells H. Effect of incision and saphenous vein grafting for peyronie’s disease on penile length and sexual satisfaction. J Urol. 2001;166:1769–72.

    CAS  Article  Google Scholar 

  16. 16.

    ASTM Standard D412. Standard test methods for vulcanized rubber and thermoplastic elastomers-tension. ASTM International. 2016. www.astm.org.

  17. 17.

    ASTM Standard D638. Standard Test Method for Tensile Properties of Plastics 1. 2014 [cited 2019 Nov 6]; Available from: http://www.ansi.org.

  18. 18.

    Dunn MG, Silver FH, Swann DA. Mechanical analysis of hypertrophic scar tissue: structural basis for apparent increased rigidity. J Invest Dermatol. 1985;84:9–13. http://www.ncbi.nlm.nih.gov/pubmed/3965583.

  19. 19.

    Jansen LH, Rottier PB. Comparison of the mechanical properties of strips of human abdominal skin excised from below and from above the umbilic. Dermatology. 1958;117:252–8. http://www.ncbi.nlm.nih.gov/pubmed/13609210.

  20. 20.

    Kadioglu A, Sanli O, Akman T, Ersay A, Guven S, Mammadov F. Graft materials in peyronie’s disease surgery: a comprehensive review. J Sexual Med. 2007;4:581–95. http://www.ncbi.nlm.nih.gov/pubmed/17419820.

  21. 21.

    Blaber J, Adair B, Antoniou A. Ncorr: open-source 2D digital image correlation matlab software. Exp Mech. 2015;55:1105–22. http://www.mathworks.com/products/matlab/.

  22. 22.

    R Core Team. R: a language and environment for statistical computing. Vienna, Austria:R Core Team; 2019. https://www.r-project.org/.

  23. 23.

    Wickham H. ggplot2: elegant graphics for data analysis. New York: Springer-Verlag; 2016. https://ggplot2.tidyverse.org.

  24. 24.

    Gefen A, Chen J, Elad D. A biomechanical model of Peyronie’s disease. J Biomech. 2000;33:1739–44.

    CAS  Article  Google Scholar 

  25. 25.

    Kelly DA. Expansion of the tunica albuginea during penile inflation in the nine-banded armadillo (Dasypus novemcinctus). J Exp Biol. 1999;202:253–65.

  26. 26.

    Mulvihill JJ, Cunnane EM, McHugh SM, Kavanagh EG, Walsh SR, Walsh MT. Mechanical, biological and structural characterization of in vitro ruptured human carotid plaque tissue. Acta Biomater. 2013;9:9027–35.

  27. 27.

    Buffinton CM, Ebenstein DM. Effect of calcification modulus and geometry on stress in models of calcified atherosclerotic plaque. Cardiovasc Eng Technol. 2014;5:244–60. https://doi.org/10.1007/s13239-014-0186-6.

  28. 28.

    Lau AG, Kindig MW, Salzar RS, Kent RW. Micromechanical modeling of calcifying human costal cartilage using the generalized method of cells. Acta Biomater. 2015;18:226–35. https://www.sciencedirect.com/science/article/pii/S1742706115000756#!.

  29. 29.

    Wymer K, Ziegelmann M, Savage J, Kohler T, Trost L. Plaque calcification: an important predictor of collagenase clostridium histolyticum treatment outcomes for men with Peyronie’s disease. Urology. 2018;119:109–14. https://www.sciencedirect.com/science/article/pii/S0090429518305636.

  30. 30.

    Lipshultz LI, Goldstein I, Seftel AD, Kaufman GJ, Smith TM, Tursi JP, et al. Clinical efficacy of collagenase Clostridium histolyticum in the treatment of Peyronie’s disease by subgroup: results from two large, double-blind, randomized, placebo-controlled, phase III studies. BJU Int. 2015;116:650–6.

    CAS  Article  Google Scholar 

  31. 31.

    Nehra A, Alterowitz R, Culkin DJ, Faraday MM, Hakim LS, Heidelbaugh JJ, et al. Peyronie’s Disease: AUA Guideline. J Urol. 2015;194:745–53.

    Article  Google Scholar 

  32. 32.

    Chan RW, Titze IR. Effect of postmortem changes and freezing on the viscoelastic properties of vocal fold tissues. Ann Biomed Eng. 2003;31:482–91. http://link.springer.com/10.1114/1.1561287.

  33. 33.

    Hemmasizadeh A, Darvish K, Autieri M. Characterization of changes to the mechanical properties of arteries due to cold storage using nanoindentation tests. Ann Biomed Eng. 2012;40:1434–42. http://link.springer.com/10.1007/s10439-011-0506-z.

  34. 34.

    Lee AH, Elliott DM. Freezing does not alter multiscale tendon mechanics and damage mechanisms in tension. Ann N Y Acad Sci. 2017;1409:85–94. http://www.ncbi.nlm.nih.gov/pubmed/29068534.

  35. 35.

    Woo SL-Y, Orlando CA, Camp JF, Akeson WH. Effects of postmortem storage by freezing on ligament tensile behavior. J Biomech. 1986;19:399–404. https://www.sciencedirect.com/science/article/pii/0021929086900163.

  36. 36.

    Nazarian A, Hermannsson BJ, Muller J, Zurakowski D, Snyder BD. Effects of tissue preservation on murine bone mechanical properties. J Biomech. 2009;42:82–6. https://www.sciencedirect.com/science/article/pii/S0021929008004892.

  37. 37.

    Brock G, Hsu GL, Nunes L, Von Heyden B, Lue TF. The anatomy of the tunica albuginea in the normal penis and Peyronie’s disease. J Urol. 1997;276–81. https://www.auajournals.org/doi/pdf/10.1016/S0022-5347%2801%2965359-X.

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Acknowledgements

The authors acknowledge assistance with µCT imaging from Prof Timothy Cox at the Small Animal Tomographic Analysis (SANTA) facility, Seattle Children’s Research Institute (now at University of Missouri-Kansas City School of Dentistry), and Dr. Tami Wolden-Hanson of the VA Puget Sound Rodent InVivo Molecular Imaging Core.

Funding

The authors acknowledge funding from the VA Puget Sound graduate student fellowship and VA RR&D Grant RX002970.

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Correspondence to William R. Ledoux.

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Brady, L., Stender, C.J., Wang, YN. et al. Mechanical characterization of fibrotic and mineralized tissue in Peyronie’s disease. Int J Impot Res (2021). https://doi.org/10.1038/s41443-021-00439-2

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