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The development of bioresorbable composite polymeric implants with high mechanical strength

Nature Materials volume 17, pages 96–103 (2018)Cite this article

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Abstract

Implants for the treatment of tissue defects should mimic the mechanical properties of the native tissue of interest and should be resorbable as well as biocompatible. In this work, we developed a scaffold from variants of poly(glycolic) acid which were braided and coated with an elastomer of poly(glycolide-co-caprolactone) and crosslinked. The coating of the scaffold with the elastomer led to higher mechanical strength in terms of compression, expansion and elasticity compared to braids without the elastomer coating. These composite scaffolds were found to have expansion properties similar to metallic stents, utilizing materials which are typically much weaker than metal. We optimized the mechanical properties of the implant by tuning the elastomer branching structure, crosslink density, and molecular weight. The scaffolds were shown to be highly resorbable following implantation in a porcine femoral artery. Biocompatibility was studied in vivo in an ovine model by implanting the scaffolds into femoral arteries. The scaffolds were able to support an expanded open lumen over 12 months in vivo and also fully resorbed by 18 months in the ovine model.

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Figure 1: Mechanical properties of the bioresorbable, self-expanding implant.
Figure 2: Creation of the strong, elastic, resorbable, self-expanding implant.
Figure 3: Mechanical properties and morphology of low- and high-elongation material.
Figure 4: Testing of 10:90/PGCL implant in vivo in swine ilio-femoral vessels.
Figure 5: Accelerated in vitro resorption time of base braids and elastomer-coated implants.
Figure 6: Histological results of elastomer-coated implants through full resorption.

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References

  1. Nishio, S. et al. Long-term (>10 years) clinical outcomes of first-in-human biodegradable poly-l-lactic acid coronary stents: Igaki–Tamai stents. Circulation 125, 2343–2353 (2012).

    Article  CAS  Google Scholar 

  2. Bunger, C. M. 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 

  3. Uurto, I. et al. Drug-eluting biodegradable poly-D/L-lactic acid vascular stents: an experimental pilot study. J. Endovasc. Ther. 12, 371–379 (2005).

    Article  Google Scholar 

  4. Onuma, Y. et al. Three-year results of clinical follow-up after a bioresorbable everolimus-eluting scaffold in patients with de novo coronary artery disease: the ABSORB trial. EuroIntervention 6, 447–453 (2010).

    Article  Google Scholar 

  5. Alexy, R. D. & Levi, D. S. Materials and manufacturing technologies available for production of a pediatric bioabsorbable stent. Biomed. Res. Int. 2013, 137958 (2013).

    Article  Google Scholar 

  6. Scheinert, D. et al. Prevalence and clinical impact of stent fractures after femoropopliteal stenting. J. Am. Coll. Cardiol. 45, 312–315 (2005).

    Article  Google Scholar 

  7. van der Giessen, W. J. et al. Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. Circulation 94, 1690–1697 (1996).

    Article  CAS  Google Scholar 

  8. Lincoff, A. M. et al. Sustained local delivery of dexamethasone by a novel intravascular eluting stent to prevent restenosis in the porcine coronary injury model. J. Am. Coll. Cardiol. 29, 808–816 (1997).

    Article  CAS  Google Scholar 

  9. Fischell, T. A. Polymer coatings for stents. Can we judge a stent by its cover? Circulation 94, 1494–1495 (1996).

    Article  CAS  Google Scholar 

  10. Venkatraman, S., Boey, F. & Lao, L. L. Implanted cardiovascular polymers: natural, synthetic and bio-inspired. Prog. Polym. Sci. 33, 853–874 (2008).

    Article  CAS  Google Scholar 

  11. Vogt, F. et al. Long-term assessment of a novel biodegradable paclitaxel-eluting coronary polylactide stent. Eur. Heart J. 25, 1330–1340 (2004).

    Article  CAS  Google Scholar 

  12. LACTEL Absorbable Polymers. Chemical & Physical Properties of Select Polymers (cited May 26, 2014); http://www.absorbables.com/technical/properties.html

  13. Nuutinen, J. P. et al. Mechanical properties and in vitro degradation of bioresorbable knitted stents. J. Biomater. Sci. Polym. Ed. 13, 1313–1323 (2002).

    Article  CAS  Google Scholar 

  14. Chen, M. C. et al. Rapidly self-expandable polymeric stents with a shape-memory property. Biomacromolecules 8, 2774–2780 (2007).

    Article  CAS  Google Scholar 

  15. Nuutinen, J. P. et al. Mechanical properties and in vitro degradation of bioabsorbable self-expanding braided stents. J. Biomater. Sci. Polym. Ed. 14, 255–266 (2003).

    Article  CAS  Google Scholar 

  16. Pulapura, S. & Kohn, J. Trends in the development of bioresorbable polymers for medical applications. J. Biomater. Appl. 6, 216–250 (1992).

    Article  CAS  Google Scholar 

  17. Chen, C. C. et al. Preparation and characterization of biodegradable PLA polymeric blends. Biomaterials 24, 1167–1173 (2003).

    Article  CAS  Google Scholar 

  18. Vert, M. et al. Bioresorbability and biocompatibility of aliphatic polyesters. J. Mater. Sci. Mater. Med. 3, 432–446 (1992).

    Article  CAS  Google Scholar 

  19. Orchel, A. et al. Growth of human chondrocytes on biodegradable synthetic polymers. Acta Pol. Pharm. 63, 455–456 (2006).

    CAS  Google Scholar 

  20. Wise, D. L. Biomaterials and Bioengineering Handbook (CRC Press, 2001).

    Google Scholar 

  21. Juan, V. C.-R. et al. Advances in Biomaterials Science and Biomedical Applications Ch. 3: Degradation of Polyurethanes for Cardiovascular Applications (InTech, 2013).

    Google Scholar 

  22. Dalene, M., Skarping, G. & Brorson, T. Chromatographic determination of amines in biological fluids with special reference to the biological monitoring of isocyanates and amines. IV. Determination of 1,6-hexamethylenediamine in human urine using capillary gas chromatography and selective ion monitoring. J. Chromatogr. 516, 405–413 (1990).

    Article  CAS  Google Scholar 

  23. Dalene, M., Skarping, G. & Tinnerberg, H. Biological monitoring of hexamethylene diisocyanate by determination of 1,6-hexamethylene diamine as the trifluoroethyl chloroformate derivative using capillary gas chromatography with thermoionic and selective-ion monitoring. J. Chromatogr. B. Biomed. Appl. 656, 319–328 (1994).

    Article  CAS  Google Scholar 

  24. Serruys, P. W. et al. Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon. A quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months. Circulation 77, 361–371 (1988).

    Article  CAS  Google Scholar 

  25. Leigh Perkins, L. E. Preclinical models of restenosis and their application in the evaluation of drug-eluting stent systems. Vet. Pathol. 47, 58–76 (2010).

    Article  Google Scholar 

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Acknowledgements

We thank J. Anderson, R. Virmani, R. Schwartz, and S. Hilbert for consultation and feedback. We acknowledge the efforts of A. Pappas, T. Ng, K. Ho, I. Gitlin, P. Zamiri, W. Naimark, A. Rago, D. Sundaresh, J. Marini, S. Morneau, M. Le, S. Varughese and K. Un in device fabrication, data collection, analytical evaluation, and manuscript review.

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Authors and Affiliations

  1. 480 Biomedical, Inc., Watertown, Massachusetts, 02472, USA

    Upma Sharma, Danny Concagh, Lee Core, Yina Kuang, Changcheng You, Quynh Pham, Greg Zugates, Rany Busold, Stephanie Webber, Jonathan Merlo & Maria Palasis

  2. Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA

    Robert Langer

  3. Harvard University, Cambridge, Massachusetts, 02138, USA

    George M. Whitesides

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Contributions

U.S., D.C., L.C., Y.K., C.Y., G.Z., R.B., S.W. and M.P. conceived the experiments. C.Y. and J.M. performed the experiments. U.S., D.C., L.C., Y.K., C.Y., Q.P., G.Z. R.B. and S.W. undertook analysis of the data and results. U.S., D.C., L.C., Y.K., C.Y, Q.P., R.L. and G.M.W. wrote the manuscript.

Corresponding author

Correspondence to Maria Palasis.

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Competing interests

Upma Sharma PhD, Danny Concagh MS, Lee Core MSE, Yina Kuang PhD, Changcheng You PhD, Quynh Pham PhD, Greg Zugates PhD, Rany Busold BS, Jonathan Merlo BS, Stephanie Webber BS and Maria Palasis PhD were employees of 480 Biomedical at the time of this work. All authors have stock options in 480 Biomedical.

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Sharma, U., Concagh, D., Core, L. et al. The development of bioresorbable composite polymeric implants with high mechanical strength. Nature Mater 17, 96–103 (2018). https://doi.org/10.1038/nmat5016

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