Biodegradable Stents: Biomechanical Modeling Challenges and Opportunities

Abstract

Biodegradable implants show great potential in many areas of medicine, and have already demonstrated success in simple applications such as sutures. For more complex devices, such as vascular stents, there are considerable challenges associated with the use of biodegradable materials. These materials typically are weaker than the metals currently used to construct stents, so it is difficult to ensure sufficient strength to prop open the artery and alleviate symptoms acutely. It is even more challenging to design a stent that provides structural support for a predictable, appropriate time to facilitate artery healing. These challenges are evident when one considers that there are no biodegradable stents on the US market despite more than 20 years of development efforts. This review summarizes previous efforts at implementing biodegradable stents, discusses the specific challenges involved, and presents a recently developed biodegradable material modeling framework that can benefit this exciting field.

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Notes

  1. 1.

    A note on terminology: Biodegradable polymers are polymers that are decomposed in the body, but whose degradation products remain in tissues. On the other hand, bioresorbable polymers can be defined as polymers that degrade after implantation into nontoxic products, which are then eliminated from the body or metabolized. Although this last term is more precise, it is often used interchangeably with absorbable, resorbable, bioabsorbable, and biodegradable.26 For the purposes of this document, “biodegradable” will encompass all of these terms.

References

  1. 1.

    Agrawal, C. M., and H. G. Clark. Deformation characteristics of a bioabsorbable intravascular stent. Invest. Radiol. 27:1020–1024, 1992.

    Article  Google Scholar 

  2. 2.

    Agrawal, C. M., K. F. Haas, D. A. Leopold, et al. Evaluation of poly(l-lactic acid) as a material for intravascular polymeric stents. Biomaterials 13:176–182, 1992.

    Article  Google Scholar 

  3. 3.

    Agrawal, C. M., and R. B. Ray. Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. J. Biomed. Mater. Res. 55:141–150, 2001.

    Article  Google Scholar 

  4. 4.

    Ali, S. A., P. J. Doherty, and D. F. Williams. Mechanisms of polymer degradation in implantable devices. 2. Poly(Dl-lactic acid). J. Biomed. Mater. Res. 27:1409–1418, 1993.

    Article  Google Scholar 

  5. 5.

    Ali, S. A., S. P. Zhong, P. J. Doherty, et al. Mechanisms of polymer degradation in implantable devices. 1. Poly(caprolactone). Biomaterials 14:648–656, 1993.

    Article  Google Scholar 

  6. 6.

    Arshady, R. Biodegradable Polymers. London: Citus Books, 2003.

    Google Scholar 

  7. 7.

    Bedoya, J., C. A. Meyer, L. H. Timmins, et al. Effects of stent design parameters on normal artery wall mechanics. J. Biomech. Eng. 128:757–765, 2006.

    Article  Google Scholar 

  8. 8.

    Bier, J. D., P. Zalesky, S. T. Li, et al. A new bioabsorbable intravascular stent: in vitro assessment of hemodynamic and morphometric characteristics. J. Interv. Cardiol. 5:187–194, 1992.

    Article  Google Scholar 

  9. 9.

    Bosiers, M., P. Peeters, O. D’Archambeau, et al. Ams insight—absorbable metal stent implantation for treatment of below-the-knee critical limb ischemia: 6-month analysis. Cardiovasc. Intervent. Radiol. 32:424–435, 2009.

    Article  Google Scholar 

  10. 10.

    Bunger, C. M., N. Grabow, K. Sternberg, et al. A biodegradable stent based on poly(l-lactide) and poly(4-hydroxybutyrate) for peripheral vascular application: preliminary experience in the pig. J. Endovasc. Ther. 14:725–733, 2007.

    Article  Google Scholar 

  11. 11.

    Bunger, C. M., N. Grabow, K. Sternberg, et al. Sirolimus-eluting biodegradable poly-l-lactide stent for peripheral vascular application: a preliminary study in porcine carotid arteries. J. Surg. Res. 139:77–82, 2007.

    Article  Google Scholar 

  12. 12.

    Burkersroda, Fv., L. Schedl, and A. Gopferich. Why degradable polymers undergo surface erosion or bulk erosion. Biomaterials 23:4221–4231, 2002.

    Article  Google Scholar 

  13. 13.

    Chu, C. C. Strain-Accelerated Hydrolytic Degradation of Synthetic Absorbable Sutures, edited by C. W. Hall. San Antonio, 1985, pp. 111–115.

  14. 14.

    Colombo, A., and E. Karvouni. Biodegradable stents: “fulfilling the mission and stepping away”. Circulation 102:371–373, 2000.

    Google Scholar 

  15. 15.

    Drynda, A., N. Deinet, N. Braun, et al. Rare earth metals used in biodegradable magnesium-based stents do not interfere with proliferation of smooth muscle cells but do induce the upregulation of inflammatory genes. J. Biomed. Mater. Res. A 91:360–369, 2009.

    Google Scholar 

  16. 16.

    Erbel, R., C. Di Mario, J. Bartunek, et al. Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial. Lancet 369:1869–1875, 2007.

    Article  Google Scholar 

  17. 17.

    Farb, A., D. K. Weber, F. D. Kolodgie, et al. Morphological predictors of restenosis after coronary stenting in humans. Circulation 105:2974–2980, 2002.

    Article  Google Scholar 

  18. 18.

    Folkman, J., and D. M. Long. The use of silicone rubber as a carrier for prolonged drug therapy. J. Surg. Res. 4:139–142, 1964.

    Article  Google Scholar 

  19. 19.

    Gopferich, A. Polymer degradation and erosion: mechanisms and applications. Eur. J. Pharm. Biopharm. 4:1–11, 1996.

    Google Scholar 

  20. 20.

    Gopferich, A. Bioerodible implants with programmable drug release. J. Control. Release 44:271–281, 1997.

    Article  Google Scholar 

  21. 21.

    Gopferich, A. Mechanisms of polymer degradation and elimination. In: Handbook of Biodegradable Polymers, edited by A. J. Domb, et al. Australia: Harwood Academic Publishers, 1997, pp. 451–471.

    Google Scholar 

  22. 22.

    Grabow, N., C. M. Bunger, C. Schultze, et al. A biodegradable slotted tube stent based on poly(l-lactide) and poly(4-hydroxybutyrate) for rapid balloon-expansion. Ann. Biomed. Eng. 35:2031–2038, 2007.

    Article  Google Scholar 

  23. 23.

    Grabow, N., H. Martin, and K. P. Schmitz. The impact of material characteristics on the mechanical properties of a poly(l-lactide) coronary stent. Biomed. Tech. (Berl) 47(Suppl 1 Pt 1):503–505, 2002.

    Article  Google Scholar 

  24. 24.

    Grabow, N., M. Schlun, K. Sternberg, et al. Mechanical properties of laser cut poly(l-lactide) micro-specimens: implications for stent design, manufacture, and sterilization. J. Biomech. Eng. 127:25–31, 2005.

    Article  Google Scholar 

  25. 25.

    Grassi, M., and G. Grassi. Mathematical modelling and controlled drug delivery: matrix systems. Curr. Drug Deliv. 2:97–116, 2005.

    Article  Google Scholar 

  26. 26.

    Hayashi, T. Biodegradable polymers for biomedical uses. Prog. Polym. Sci. 19:663–702, 1994.

    Article  Google Scholar 

  27. 27.

    Heublein, B., R. Rohde, V. Kaese, et al. Biocorrosion of magnesium alloys: a new principle in cardiovascular implant technology? Heart 89:651–656, 2003.

    Article  Google Scholar 

  28. 28.

    Hietala, E. M., U. S. Salminen, A. Stahls, et al. Biodegradation of the copolymeric polylactide stent. Long-term follow-up in a rabbit aorta model. J. Vasc. Res. 38:361–369, 2001.

    Article  Google Scholar 

  29. 29.

    Hyon, S. H., K. Jamshidi, and Y. Ikada. Effects of residual monomer on the degradation of Dl-lactide polymer. Polym. Int. 46:196–202, 1998.

    Article  Google Scholar 

  30. 30.

    Kastrati, A., D. Hall, and A. Schomig. Long-term outcome after coronary stenting. Curr. Contr. Trials C 1:48–54, 2000.

    Article  Google Scholar 

  31. 31.

    Katti, D. S., S. Lakshmi, R. Langer, et al. Toxicity, biodegradation and elimination of polyanhydrides. Adv. Drug Deliv. Rev. 54:933–961, 2002.

    Article  Google Scholar 

  32. 32.

    Kimura, T., H. Yokoi, Y. Nakagawa, et al. Three-year follow-up after implantation of metallic coronary-artery stents. N. Engl. J. Med. 334:561–566, 1996.

    Article  Google Scholar 

  33. 33.

    Kolachalama, V. B., A. R. Tzafriri, D. Y. Arifin, et al. Luminal flow patterns dictate arterial drug deposition in stent-based delivery. J. Control. Release 133:24–30, 2009.

    Article  Google Scholar 

  34. 34.

    Labinaz, M., J. P. Zidar, R. S. Stack, et al. Biodegradable stents: the future of interventional cardiology? J. Interv. Cardiol. 8:395–405, 1995.

    Article  Google Scholar 

  35. 35.

    Langer, R. Drug delivery and targeting. Nature 392:5–10, 1998.

    Google Scholar 

  36. 36.

    Laufman, H., and T. Rubel. Synthetic absorable sutures. Surg. Gynecol. Obstet. 145:597–608, 1977.

    Google Scholar 

  37. 37.

    Li, S. M., and S. McCarthy. Further investigations on the hydrolytic degradation of poly(Dl-lactide). Biomaterials 20:35–44, 1999.

    Article  Google Scholar 

  38. 38.

    Li, S. M., and M. Vert. Morphological-changes resulting from the hydrolytic degradation of stereocopolymers derived from L-lactides and Dl-lactides. Macromolecules 27:3107–3110, 1994.

    Article  Google Scholar 

  39. 39.

    Maeng, M., L. O. Jensen, E. Falk, et al. Negative vascular remodelling after implantation of bioabsorbable magnesium alloy stents in porcine coronary arteries: a randomised comparison with bare-metal and sirolimus-eluting stents. Heart 95:241–246, 2009.

    Article  Google Scholar 

  40. 40.

    Mikkonen, J., I. Uurto, T. Isotalo, et al. Drug-eluting bioabsorbable stents—an in vitro study. Acta Biomater. 5:2894–2900, 2009.

    Article  Google Scholar 

  41. 41.

    Miller, R. A., J. M. Brady, and D. E. Cutright. Degradation rates of oral resorbable implants (polylactates and polyglycolates): rate modification with changes in Pla/Pga copolymer ratios. J. Biomed. Mater. Res. 11:711–719, 1977.

    Article  Google Scholar 

  42. 42.

    Miller, N. D., and D. F. Williams. The in vivo and in vitro degradation of poly(glycolic acid) suture material as a function of applied strain. Biomaterials 5:365–368, 1984.

    Article  Google Scholar 

  43. 43.

    Nuutinen, J. P., C. Clerc, R. Reinikainen, et al. Mechanical properties and in vitro degradation of bioabsorbable self-expanding braided stents. J. Biomater. Sci. Polym. Ed. 14:255–266, 2003.

    Article  Google Scholar 

  44. 44.

    Nuutinen, J. P., C. Clerc, and P. Tormala. Theoretical and experimental evaluation of the radial force of self-expanding braided bioabsorbable stents. J. Biomater. Sci. Polym. Ed. 14:677–687, 2003.

    Article  Google Scholar 

  45. 45.

    Ormiston, J. A., P. W. Serruys, E. Regar, et al. A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (absorb): a prospective open-label trial. Lancet 371:899–907, 2008.

    Article  Google Scholar 

  46. 46.

    Ormiston, J. A., M. W. Webster, and G. Armstrong. First-in-human implantation of a fully bioabsorbable drug-eluting stent: the Bvs poly-l-lactic acid everolimus-eluting coronary stent. Catheter. Cardiovasc. Interv. 69:128–131, 2007.

    Article  Google Scholar 

  47. 47.

    Palminteri, E. Stents and urethral strictures: A lesson learned? Eur. Urol. 54:498–500, 2008.

    Article  Google Scholar 

  48. 48.

    Peuster, M., C. Hesse, T. Schloo, et al. Long-term biocompatibility of a corrodible peripheral iron stent in the porcine descending aorta. Biomaterials 27:4955–4962, 2006.

    Article  Google Scholar 

  49. 49.

    Peuster, M., P. Wohlsein, M. Brugmann, et al. A novel approach to temporary stenting: degradable cardiovascular stents produced from corrodible metal-results 6–18 months after implantation into New Zealand white rabbits. Heart 86:563–569, 2001.

    Article  Google Scholar 

  50. 50.

    Pietrzak, W. S., M. L. Verstynen, and D. R. Sarver. Bioabsorbable fixation devices: status for the craniomaxillofacial surgeon. J. Craniofac. Surg. 8:92–96, 1997.

    Article  Google Scholar 

  51. 51.

    Piskin, E., A. Tuncel, A. Denizli, et al. Nondegradable and biodegradable polymeric particles—preparation and some selected biomedical applications. In: Diagnostic Biosensor Polymers, edited by A. M. Usmani, et al. Washington: American Chemical Society, 1994, pp. 222–237.

    Google Scholar 

  52. 52.

    Pistner, H., D. R. Bendix, J. Muhling, et al. Poly(l-lactide)—a long-term degradation study in vivo. 3. Analytical characterization. Biomaterials 14:291–298, 1993.

    Article  Google Scholar 

  53. 53.

    Rajasubramanian, G., R. S. Meidell, C. Landau, et al. Fabrication of resorbable microporous intravascular stents for gene therapy applications. ASAIO J. 40:M584–M589, 1994.

    Article  Google Scholar 

  54. 54.

    Ramcharitar, S., and P. W. Serruys. Fully biodegradable coronary stents: progress to date. Am. J. Cardiovasc. Drugs 8:305–314, 2008.

    Article  Google Scholar 

  55. 55.

    Serruys, P. W., J. A. Ormiston, Y. Onuma, et al. A bioabsorbable everolimus-eluting coronary stent system (absorb): 2-year outcomes and results from multiple imaging methods. Lancet 373:897–910, 2009.

    Article  Google Scholar 

  56. 56.

    Soares, J. S. Constitutive modeling of biodegradable polymers for application in endovascular stents. PhD Dissertation. College Station, TX: Texas A&M University, 2008.

  57. 57.

    Soares, J. S. Diffusion of a fluid through a spherical elastic solid undergoing large deformations. Int. J. Eng. Sci. 47:50–63, 2009.

    Article  MathSciNet  Google Scholar 

  58. 58.

    Soares, J. S., J. E. Moore, Jr., and K. R. Rajagopal. Theoretical modeling of cyclically loaded biodegradable cylinders. In: Modeling Biological Materials, edited by F. Mollica, et al. Boston: Birkhauser, 2007, pp. 125–177.

    Google Scholar 

  59. 59.

    Soares, J. S., J. E. Moore, and K. R. Rajagopal. Constitutive framework for biodegradable polymers with applications to biodegradable stents. ASAIO J. 54:295–301, 2008.

    Article  Google Scholar 

  60. 60.

    Soares, J. S., J. E. Moore, and K. R. Rajagopal. Modeling of deformation-accelerated breakdown of polylactic acid biodegradable stents (submitted).

  61. 61.

    Soares, J. S., K. R. Rajagopal, and J. E. Moore. Deformation-induced hydrolysis of a degradable polymeric cylindrical annulus. Biomech. Model. Mechanobiol. (in press).

  62. 62.

    Soares, J. S., and P. Zunino. A mixture model for water uptake, degradation, erosion, and drug release from polydisperse polymeric networks. Biomaterials 31:3032–3042, 2010.

    Article  Google Scholar 

  63. 63.

    Stack, R. S., R. M. Califf, H. R. Phillips, et al. Interventional cardiac catheterization at duke medical center. Am. J. Cardiol. 62:3F–24F, 1988.

    Article  Google Scholar 

  64. 64.

    Stone, G. W., S. G. Ellis, D. A. Cox, et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N. Engl. J. Med. 350:221–231, 2004.

    Article  Google Scholar 

  65. 65.

    Su, S. H., R. Y. Chao, C. L. Landau, et al. Expandable bioresorbable endovascular stent. I. Fabrication and properties. Ann. Biomed. Eng. 31:667–677, 2003.

    Article  Google Scholar 

  66. 66.

    Suggs, L. J., R. S. Krishnan, C. A. Garcia, et al. In vitro and in vivo degradation of poly(propylene fumarate-co-ethylene glycol) hydrogels. J. Biomed. Mater. Res. 42:312–320, 1998.

    Article  Google Scholar 

  67. 67.

    Tamada, J. A., and R. Langer. Erosion kinetics of hydrolytically degradable polymers. Proc. Natl. Acad. Sci. USA 90:552–556, 1993.

    Article  Google Scholar 

  68. 68.

    Tamai, H., K. Igaki, E. Kyo, et al. Initial and 6-month results of biodegradable poly-l-lactic acid coronary stents in humans. Circulation 102:399–404, 2000.

    Google Scholar 

  69. 69.

    Tamai, H., K. Igaki, T. Tsuji, et al. A biodegradable poly-l-lactic acid coronary stent in the porcine coronary artery. J. Interv. Cardiol. 12:443–449, 1999.

    Article  Google Scholar 

  70. 70.

    Tammela, T. L., and M. Talja. Biodegradable urethral stents. BJU Int. 92:843–850, 2003.

    Article  Google Scholar 

  71. 71.

    Tanguay, J. F., J. P. Zidar, H. R. Phillips, 3rd, et al. Current status of biodegradable stents. Cardiol. Clin. 12:699–713, 1994.

    Google Scholar 

  72. 72.

    Tsuji, T., H. Tamai, K. Igaki, et al. Biodegradable stents as a platform to drug loading. Int. J. Cardiovasc. Intervent. 5:13–16, 2003.

    Google Scholar 

  73. 73.

    Uurto, I., A. Kotsar, T. Isotalo, et al. Tissue biocompatibility of new biodegradable drug-eluting stent materials. J. Mater. Sci. Mater. Med. 18:1543–1547, 2007.

    Article  Google Scholar 

  74. 74.

    Waksman, R., R. Erbel, C. Di Mario, et al. Early- and long-term intravascular ultrasound and angiographic findings after bioabsorbable magnesium stent implantation in human coronary arteries. JACC Cardiovasc. Interv. 2:312–320, 2009.

    Article  Google Scholar 

  75. 75.

    Weir, N. A., F. J. Buchanan, J. F. Orr, et al. Degradation of poly-l-lactide: part 1: in vitro and in vivo physiological temperature degradation. P. I. Mech. Eng. H 218:307–319, 2004.

    Article  Google Scholar 

  76. 76.

    Weir, N. A., F. J. Buchanan, J. F. Orr, et al. Degradation of poly-l-lactide: part 2: increased temperature accelerated degradation. P. I. Mech. Eng. H 218:321–330, 2004.

    Article  Google Scholar 

  77. 77.

    Welch, T., R. C. Eberhart, and C. J. Chuong. Characterizing the expansive deformation of a bioresorbable polymer fiber stent. Ann. Biomed. Eng. 36:742–751, 2008.

    Article  Google Scholar 

  78. 78.

    Wiggins, M. J., J. M. Anderson, and A. Hiltner. Effect of strain and strain rate on fatigue-accelerated biodegradation of polyurethane. J. Biomed. Mater. Res. A 66A:463–475, 2003.

    Article  Google Scholar 

  79. 79.

    Wiggins, M. J., J. M. Anderson, and A. Hiltner. Biodegradation of polyurethane under fatigue loading. J. Biomed. Mater. Res. A 65A:524–535, 2003.

    Article  Google Scholar 

  80. 80.

    Wiggins, M. J., M. MacEwan, J. M. Anderson, et al. Effect of soft-segment chemistry on polyurethane biostability during in vitro fatigue loading. J. Biomed. Mater. Res. A 68A:668–683, 2004.

    Article  Google Scholar 

  81. 81.

    Wu, X. S., and N. Wang. Characterization, biodegradation, and drug delivery application of biodegradable lactic/glycolic acid polymers. Part II: biodegradation. J. Biomater. Sci. Polym. Ed. 12:21–34, 2001.

    Article  Google Scholar 

  82. 82.

    Ye, Y. W., C. Landau, J. E. Willard, et al. Bioresorbable microporous stents deliver recombinant adenovirus gene transfer vectors to the arterial wall. Ann. Biomed. Eng. 26:398–408, 1998.

    Article  Google Scholar 

  83. 83.

    Zhang, Y., S. Zale, L. Sawyer, et al. Effects of metal salts on poly(Dl-lactide-co-glycolide) polymer hydrolysis. J. Biomed. Mater. Res. 34:531–538, 1997.

    Article  Google Scholar 

  84. 84.

    Zhong, S. P., P. J. Doherty, and D. F. Williams. The effect of applied strain on the degradation of absorbable suture in vitro. Clin. Mater. 14:183–189, 1993.

    Article  Google Scholar 

  85. 85.

    Zilberman, M., K. D. Nelson, and R. C. Eberhart. Mechanical properties and in vitro degradation of bioresorbable fibers and expandable fiber-based stents. J. Biomed. Mater. Res. B 74:792–799, 2005.

    Google Scholar 

  86. 86.

    Zilberman, M., N. D. Schwade, and R. C. Eberhart. Protein-loaded bioresorbable fibers and expandable stents: mechanical properties and protein release. J. Biomed. Mater. Res. B 69:1–10, 2004.

    Article  Google Scholar 

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Acknowledgments

The authors gratefully acknowledge support from the National Institutes of Health (R01 EB000115 to JEM), the Portuguese Fundação para a Ciência e Tecnologia (SFRH/BD/17060/2004 and SFRH/BPD/63119/2009 to JSS), and the National Science Foundation (to KRR).

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Moore, J.E., Soares, J.S. & Rajagopal, K.R. Biodegradable Stents: Biomechanical Modeling Challenges and Opportunities. Cardiovasc Eng Tech 1, 52–65 (2010). https://doi.org/10.1007/s13239-010-0005-7

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Keywords

  • Polymer
  • Corrodible metals
  • Scission
  • Degradation
  • Erosion
  • Mechanical properties