Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Design of biodegradable, implantable devices towards clinical translation

Abstract

Biodegradable materials, including natural and synthetic polymers and hydrolyzable metals, constitute the main components of temporary, implantable medical devices. Besides the intrinsic properties of the materials, the most critical factor determining the successful clinical outcome of implantable and degradable devices is the host response, particularly the immune response, which largely depends on the material features and degradation mechanisms. In this Review, we first survey the state of the art in terms of materials options for use in biodegradable medical devices, focusing on degradation mechanisms and their control. In particular, we highlight silk, which is emerging as an important polymer, owing to its mechanical robustness, bioactive component sequestration, degradability without problematic metabolic products and biocompatibility. We then discuss the host response to these biodegradable materials in terms of dynamic tissue–implant interfaces. Next, we examine the clinical translation of three leading biodegradable material systems — natural and synthetic biodegradable polymers and biodegradable metals — and the related challenges in the context of orthopaedic fixation devices, cardiovascular stents and biodegradable electronic devices. Looking to the future, we propose updated material design strategies to improve the clinical outcomes for these biodegradable medical devices.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Host response to implanted materials and devices.
Fig. 2: Schematic overview of in vivo biodegradation of various materials.
Fig. 3: 3D silk materials for the fabrication of orthopaedic fixation devices.
Fig. 4: Biodegradable electronic devices.
Fig. 5: Design of biodegradable medical devices.

Similar content being viewed by others

References

  1. Kurtz, S., Ong, K., Lau, E., Mowat, F. & Halpern, M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J. Bone Joint Surg. Am. 89, 780–785 (2007).

    Google Scholar 

  2. Cobelli, N., Scharf, B., Crisi, G. M., Hardin, J. & Santambrogio, L. Mediators of the inflammatory response to joint replacement devices. Nat. Rev. Rheumatol. 7, 600–608 (2011).

    CAS  Google Scholar 

  3. Hubbell, J. A. & Langer, R. Translating materials design to the clinic. Nat. Mater. 12, 963–966 (2013).

    CAS  Google Scholar 

  4. Farra, R. et al. First-in-human testing of a wirelessly controlled drug delivery microchip. Sci. Transl Med. 4, 122ra121 (2012).

    Google Scholar 

  5. Nichols, S. P., Koh, A., Storm, W. L., Shin, J. H. & Schoenfisch, M. H. Biocompatible materials for continuous glucose monitoring devices. Chem. Rev. 113, 2528–2549 (2013).

    CAS  Google Scholar 

  6. Rosen, M. R., Robinson, R. B., Brink, P. R. & Cohen, I. S. The road to biological pacing. Nat. Rev. Cardiol. 8, 656–666 (2011).

    Google Scholar 

  7. Wykrzykowska, J. J. et al. Bioresorbable scaffolds versus metallic stents in routine PCI. N. Engl. J. Med. 376, 2319–2328 (2017).

    CAS  Google Scholar 

  8. Devi, K. S. & Vasudevan, P. Absorbable surgical sutures. J. Macromol. Sci. C 25, 315–324 (1985).

    Google Scholar 

  9. Hjort, H., Mathisen, T., Alves, A., Clermont, G. & Boutrand, J. P. Three-year results from a preclinical implantation study of a long-term resorbable surgical mesh with time-dependent mechanical characteristics. Hernia 16, 191–197 (2012).

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  11. Cassese, S. et al. Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials. Lancet 387, 537–544 (2016).

    CAS  Google Scholar 

  12. Cha, G. D., Kang, D., Lee, J. & Kim, D. H. Bioresorbable electronic implants: history, materials, fabrication, devices, and clinical applications. Adv. Healthc. Mater. 8, e1801660 (2019).

    Google Scholar 

  13. Liu, Y., Zheng, Y. & Hayes, B. Degradable, absorbable or resorbable — what is the best grammatical modifier for an implant that is eventually absorbed by the body? Sci. China Mater. 60, 377–391 (2017).

    CAS  Google Scholar 

  14. Anderson, J. M., Rodriguez, A. & Chang, D. T. Foreign body reaction to biomaterials. Semin. Immunol. 20, 86–100 (2008).

    CAS  Google Scholar 

  15. Chandorkar, Y., Ravikumar, K. & Basu, B. The foreign body response demystified. ACS Biomater. Sci. Eng. 5, 19–44 (2019).

    Google Scholar 

  16. Kumar, V., Abbas, A. K., & Aster, J. C. Robbins & Cotran Pathologic Basis of Disease 9th edn (Elsevier/Saunders, 2015).

  17. Julier, Z., Park, A. J., Briquez, P. S. & Martino, M. M. Promoting tissue regeneration by modulating the immune system. Acta Biomater. 53, 13–28 (2017).

    CAS  Google Scholar 

  18. Woodruff, M. A. & Hutmacher, D. W. The return of a forgotten polymer — polycaprolactone in the 21st century. Prog. Polym. Sci. 35, 1217–1256 (2010).

    CAS  Google Scholar 

  19. Iwasaki, A. & Medzhitov, R. Regulation of adaptive immunity by the innate immune system. Science 327, 291–295 (2010).

    CAS  Google Scholar 

  20. Franz, S., Rammelt, S., Scharnweber, D. & Simon, J. C. Immune responses to implants – a review of the implications for the design of immunomodulatory biomaterials. Biomaterials 32, 6692–6709 (2011).

    CAS  Google Scholar 

  21. Nilsson, B., Korsgren, O., Lambris, J. D. & Ekdahl, K. N. Can cells and biomaterials in therapeutic medicine be shielded from innate immune recognition? Trends Immunol. 31, 32–38 (2010).

    CAS  Google Scholar 

  22. Mantovani, A., Biswas, S. K., Galdiero, M. R., Sica, A. & Locati, M. Macrophage plasticity and polarization in tissue repair and remodelling. J. Pathol. 229, 176–185 (2013).

    CAS  Google Scholar 

  23. Sica, A. & Mantovani, A. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest. 122, 787–795 (2012).

    CAS  Google Scholar 

  24. Mantovani, A. et al. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 25, 677–686 (2004).

    CAS  Google Scholar 

  25. Wynn, T. A. & Vannella, K. M. Macrophages in tissue repair, regeneration, and fibrosis. Immunity 44, 450–462 (2016).

    CAS  Google Scholar 

  26. Wynn, T. A. & Barron, L. Macrophages: master regulators of inflammation and fibrosis. Semin. Liver Dis. 30, 245–257 (2010).

    CAS  Google Scholar 

  27. Willenborg, S. et al. CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair. Blood 120, 613–625 (2012).

    CAS  Google Scholar 

  28. Murray, P. J. & Wynn, T. A. Protective and pathogenic functions of macrophage subsets. Nat. Rev. Immunol. 11, 723–737 (2011).

    CAS  Google Scholar 

  29. Shouval, D. S. et al. Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. Immunity 40, 706–719 (2014).

    CAS  Google Scholar 

  30. Zigmond, E. et al. Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis. Immunity 40, 720–733 (2014).

    CAS  Google Scholar 

  31. Raimondo, T. M. & Mooney, D. J. Functional muscle recovery with nanoparticle-directed M2 macrophage polarization in mice. Proc. Natl Acad. Sci. USA 115, 10648–10653 (2018).

    CAS  Google Scholar 

  32. Brown, B. N., Sicari, B. M. & Badylak, S. F. Rethinking regenerative medicine: a macrophage-centered approach. Front. Immunol. 5, 510 (2014).

    Google Scholar 

  33. Agrawal, V. et al. Epimorphic regeneration approach to tissue replacement in adult mammals. Proc. Natl Acad. Sci. USA 107, 3351–3355 (2010).

    CAS  Google Scholar 

  34. Biswas, S. K. & Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 11, 889–896 (2010).

    CAS  Google Scholar 

  35. Scarritt, M. E., Londono, R. & Badylak, S. F. in The Immune Response to Implanted Materials and Devices: The Impact of the Immune System on the Success of an Implant (ed. Corradetti, B.) 1–14 (Springer, 2017).

  36. Sadtler, K. et al. Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells. Science 352, 366–370 (2016).

    CAS  Google Scholar 

  37. Feiner, R. & Dvir, T. Tissue–electronics interfaces: from implantable devices to engineered tissues. Nat. Rev. Mater. 3, 17076 (2017).

    Google Scholar 

  38. Moshayedi, P. et al. The relationship between glial cell mechanosensitivity and foreign body reactions in the central nervous system. Biomaterials 35, 3919–3925 (2014).

    CAS  Google Scholar 

  39. Nguyen, J. K. et al. Mechanically-compliant intracortical implants reduce the neuroinflammatory response. J. Neural. Eng. 11, 056014 (2014).

    Google Scholar 

  40. Rivnay, J., Wang, H., Fenno, L., Deisseroth, K. & Malliaras, G. G. Next-generation probes, particles, and proteins for neural interfacing. Science Adv. 3, e1601649 (2017).

    Google Scholar 

  41. Subbaroyan, J., Martin, D. C. & Kipke, D. R. A finite-element model of the mechanical effects of implantable microelectrodes in the cerebral cortex. J. Neural Eng. 2, 103–113 (2005).

    Google Scholar 

  42. Veiseh, O. et al. Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat. Mater. 14, 643–651 (2015).

    CAS  Google Scholar 

  43. Sanders, J. E., Stiles, C. E. & Hayes, C. L. Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density. J. Biomed. Mater. Res. 52, 231–237 (2000).

    CAS  Google Scholar 

  44. Matlaga, B. F., Yasenchak, L. P. & Salthouse, T. N. Tissue response to implanted polymers: the significance of sample shape. J. Biomed. Mater. Res. 10, 391–397 (1976).

    CAS  Google Scholar 

  45. Salthouse, T. N. Some aspects of macrophage behavior at the implant interface. J. Biomed. Mater. Res. 18, 395–401 (1984).

    CAS  Google Scholar 

  46. Madden, L. R. et al. Proangiogenic scaffolds as functional templates for cardiac tissue engineering. Proc. Natl Acad. Sci. USA 107, 15211–15216 (2010).

    CAS  Google Scholar 

  47. Sussman, E. M., Halpin, M. C., Muster, J., Moon, R. T. & Ratner, B. D. Porous implants modulate healing and induce shifts in local macrophage polarization in the foreign body reaction. Ann. Biomed. Eng. 42, 1508–1516 (2014).

    Google Scholar 

  48. Young, J. L. et al. In vivo response to dynamic hyaluronic acid hydrogels. Acta Biomater. 9, 7151–7157 (2013).

    CAS  Google Scholar 

  49. Amini, A. R., Wallace, J. S. & Nukavarapu, S. P. Short-term and long-term effects of orthopedic biodegradable implants. J. Long Term Eff. Med. Implants 21, 93–122 (2011).

    CAS  Google Scholar 

  50. Gallagher, W. M. et al. Molecular basis of cell–biomaterial interaction: insights gained from transcriptomic and proteomic studies. Biomaterials 27, 5871–5882 (2006).

    CAS  Google Scholar 

  51. Boss, J. H., Shajrawi, I., Aunullah, J. & Mendes, D. G. The relativity of biocompatibility. a critique of the concept of biocompatibility. Isr. J. Med. Sci. 31, 203–209 (1995).

    CAS  Google Scholar 

  52. Siebers, M. C., ter Brugge, P. J., Walboomers, X. F. & Jansen, J. A. Integrins as linker proteins between osteoblasts and bone replacing materials. A critical review. Biomaterials 26, 137–146 (2005).

    CAS  Google Scholar 

  53. Nuss, K. M. & von Rechenberg, B. Biocompatibility issues with modern implants in bone - a review for clinical orthopedics. Open Orthop. J. 2, 66–78 (2008).

    Google Scholar 

  54. Ekdahl, K. N. et al. Innate immunity activation on biomaterial surfaces: a mechanistic model and coping strategies. Adv. Drug Del. Rev. 63, 1042–1050 (2011).

    CAS  Google Scholar 

  55. Xu, L.-C., Bauer, J. W. & Siedlecki, C. A. Proteins, platelets, and blood coagulation at biomaterial interfaces. Colloids Surf. B Biointerfaces 124, 49–68 (2014).

    CAS  Google Scholar 

  56. Engberg, A. E. et al. Blood protein-polymer adsorption: implications for understanding complement-mediated hemoincompatibility. J. Biomed. Mater. Res. A 97A, 74–84 (2011).

    CAS  Google Scholar 

  57. Ferraz, N., Ott, M. K. & Hong, J. Time sequence of blood activation by nanoporous alumina: studies on platelets and complement system. Microsc. Res. Tech. 73, 1101–1109 (2010).

    CAS  Google Scholar 

  58. Willumeit-Römer, R. The interface between degradable Mg and tissue. JOM 71, 1447–1455 (2019).

    Google Scholar 

  59. Lee, J.-W. et al. Long-term clinical study and multiscale analysis of in vivo biodegradation mechanism of Mg alloy. Proc. Natl Acad. Sci. USA 113, 716–721 (2016).

    CAS  Google Scholar 

  60. Kenawy, H. I., Boral, I. & Bevington, A. Complement-coagulation cross-talk: a potential mediator of the physiological activation of complement by low pH. Front. Immunol. 6, 215 (2015).

    Google Scholar 

  61. Yang, H. et al. Evolution of the degradation mechanism of pure zinc stent in the one-year study of rabbit abdominal aorta model. Biomaterials 145, 92–105 (2017).

    CAS  Google Scholar 

  62. Holland, C., Numata, K., Rnjak-Kovacina, J. & Seib, F. P. The biomedical use of silk: past, present, future. Adv. Healthc. Mater. 8, 1800465 (2019).

    Google Scholar 

  63. Huang, W., Ling, S., Li, C., Omenetto, F. G. & Kaplan, D. L. Silkworm silk-based materials and devices generated using bio-nanotechnology. Chem. Soc. Rev. 47, 6486–6504 (2018).

    CAS  Google Scholar 

  64. Zhou, Z. et al. Engineering the future of silk materials through advanced manufacturing. Adv. Mater. 30, 1706983 (2018).

    Google Scholar 

  65. Keane, T. J., Swinehart, I. T. & Badylak, S. F. Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance. Methods 84, 25–34 (2015).

    CAS  Google Scholar 

  66. Brown, B. N. & Badylak, S. F. in Translating Regenerative Medicine to the Clinic (ed. Laurence, J.) 11–29 (Academic, 2016).

  67. Huleihel, L. et al. Matrix-bound nanovesicles within ECM bioscaffolds. Science Adv. 2, e1600502 (2016).

    Google Scholar 

  68. Christman, K. L. Biomaterials for tissue repair. Science 363, 340–341 (2019).

    CAS  Google Scholar 

  69. Prestwich, G. D. & Atzet, S. in Biomaterials Science 3rd edn (eds Ratner, B. D., Hoffman, A. S., Schoen, F. J. & Lemons, J. E.) 195–209 (Academic, 2013).

  70. Schmitt, E. E. & Polistina, R. A. Surgical sutures. US patent US3297033A (1967).

  71. Schmitt, E. E., Epstein, M. & Polistina, R. A. Process for polymerizing a glycolide. US patent US3442871A (1969).

  72. Schmitt, E. E. & Polistina, R. A. Polyglycolic acid prosthetic devices. US patent US3463158A (1969).

  73. Middleton, J. C. & Tipton, A. J. Synthetic biodegradable polymers as orthopedic devices. Biomaterials 21, 2335–2346 (2000).

    CAS  Google Scholar 

  74. Nair, L. S. & Laurencin, C. T. Biodegradable polymers as biomaterials. Prog. Polym. Sci. 32, 762–798 (2007).

    CAS  Google Scholar 

  75. Vroman, I. & Tighzert, L. Biodegradable polymers. Materials 2, 307–344 (2009).

    CAS  Google Scholar 

  76. Tian, H., Tang, Z., Zhuang, X., Chen, X. & Jing, X. Biodegradable synthetic polymers: preparation, functionalization and biomedical application. Prog. Polym. Sci. 37, 237–280 (2012).

    CAS  Google Scholar 

  77. McMahon, S. et al. Bio-resorbable polymer stents: a review of material progress and prospects. Prog. Polym. Sci. 83, 79–96 (2018).

    CAS  Google Scholar 

  78. Regazzoli, D., Leone, P. P., Colombo, A. & Latib, A. New generation bioresorbable scaffold technologies: an update on novel devices and clinical results. J. Thorac. Dis. 9, S979–S985 (2017).

    Google Scholar 

  79. Ulery, B. D., Nair, L. S. & Laurencin, C. T. Biomedical applications of biodegradable polymers. J. Polym. Sci. B Polym. Phys. 49, 832–864 (2011).

    CAS  Google Scholar 

  80. Hermawan, H. Updates on the research and development of absorbable metals for biomedical applications. Prog. Biomater. 7, 93–110 (2018).

    CAS  Google Scholar 

  81. Venezuela, J. & Dargusch, M. S. The influence of alloying and fabrication techniques on the mechanical properties, biodegradability and biocompatibility of zinc: a comprehensive review. Acta Biomater. 87, 1–40 (2019).

    CAS  Google Scholar 

  82. Han, H.-S. et al. Current status and outlook on the clinical translation of biodegradable metals. Mater. Today 23, 57–71 (2019).

    CAS  Google Scholar 

  83. Bowen, P. K., Drelich, J. & Goldman, J. Zinc exhibits ideal physiological corrosion behavior for bioabsorbable stents. Adv. Mater. 25, 2577–2582 (2013).

    CAS  Google Scholar 

  84. Mostaed, E., Sikora-Jasinska, M., Drelich, J. W. & Vedani, M. Zinc-based alloys for degradable vascular stent applications. Acta Biomater. 71, 1–23 (2018).

    CAS  Google Scholar 

  85. Haude, M. et al. Safety and performance of the second-generation drug-eluting absorbable metal scaffold in patients with de-novo coronary artery lesions (BIOSOLVE-II): 6 month results of a prospective, multicentre, non-randomised, first-in-man trial. Lancet 387, 31–39 (2016).

    CAS  Google Scholar 

  86. Yin, L. et al. Dissolvable metals for transient electronics. Adv. Funct. Mater. 24, 645–658 (2014).

    CAS  Google Scholar 

  87. Laskin, D. L., Sunil, V. R., Gardner, C. R. & Laskin, J. D. Macrophages and tissue injury: agents of defense or destruction? Annu. Rev. Pharmacol. Toxicol. 51, 267–288 (2011).

    CAS  Google Scholar 

  88. Xia, Z. & Triffitt, J. A review on macrophage responses to biomaterials. Biomed. Mater. 1, R1–R9 (2006).

    CAS  Google Scholar 

  89. Horan, R. L. et al. In vitro degradation of silk fibroin. Biomaterials 26, 3385–3393 (2005).

    CAS  Google Scholar 

  90. Brown, J., Lu, C. L., Coburn, J. & Kaplan, D. L. Impact of silk biomaterial structure on proteolysis. Acta Biomater. 11, 212–221 (2015).

    CAS  Google Scholar 

  91. Wang, Y. et al. In vivo degradation of three-dimensional silk fibroin scaffolds. Biomaterials 29, 3415–3428 (2008).

    CAS  Google Scholar 

  92. Brown, B., Lindberg, K., Reing, J., Stolz, D. B. & Badylak, S. F. The basement membrane component of biologic scaffolds derived from extracellular matrix. Tissue Eng. 12, 519–526 (2006).

    CAS  Google Scholar 

  93. Bonnans, C., Chou, J. & Werb, Z. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol. 15, 786–801 (2014).

    CAS  Google Scholar 

  94. Lu, P., Takai, K., Weaver, V. M. & Werb, Z. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb. Perspect. Biol. 3, a005058 (2011).

    Google Scholar 

  95. Gilbert, T. W., Stewart-Akers, A. M. & Badylak, S. F. A quantitative method for evaluating the degradation of biologic scaffold materials. Biomaterials 28, 147–150 (2007).

    CAS  Google Scholar 

  96. Valentin, J. E., Stewart-Akers, A. M., Gilbert, T. W. & Badylak, S. F. Macrophage participation in the degradation and remodeling of extracellular matrix scaffolds. Tissue Eng. Part A 15, 1687–1694 (2009).

    CAS  Google Scholar 

  97. Carey, L. E. et al. In vivo degradation of 14C-labeled porcine dermis biologic scaffold. Biomaterials 35, 8297–8304 (2014).

    CAS  Google Scholar 

  98. Azevedo, H. S. & Reis, R. L. in Biodegradable Systems in Tissue Engineering and Regenerative Medicine Ch. 12 (eds Reis, R. L. & Román, J. S.) (CRC, 2004).

  99. Xie, F. et al. Degradation and stabilization of polyurethane elastomers. Prog. Polym. Sci. 90, 211–268 (2019).

    CAS  Google Scholar 

  100. Burkersroda, Fv, Schedl, L. & Göpferich, A. Why degradable polymers undergo surface erosion or bulk erosion. Biomaterials 23, 4221–4231 (2002).

    Google Scholar 

  101. Shasteen, C. & Choy, Y. B. Controlling degradation rate of poly(lactic acid) for its biomedical applications. Biomed. Eng. Lett. 1, 163–167 (2011).

    Google Scholar 

  102. Jin, L., Wu, J., Yuan, G. & Chen, T. In vitro study of the inflammatory cells response to biodegradable Mg-based alloy extract. PLOS ONE 13, e0193276 (2018).

    Google Scholar 

  103. Agarwal, S., Curtin, J., Duffy, B. & Jaiswal, S. Biodegradable magnesium alloys for orthopaedic applications: a review on corrosion, biocompatibility and surface modifications. Mater. Sci. Eng. C 68, 948–963 (2016).

    CAS  Google Scholar 

  104. Shuai, C. et al. Biodegradable metallic bone implants. Mater. Chem. Front. 3, 544–562 (2019).

    CAS  Google Scholar 

  105. Zheng, Y. F., Gu, X. N. & Witte, F. Biodegradable metals. Mater. Sci. Eng. R Rep. 77, 1–34 (2014).

    Google Scholar 

  106. Zhang, J. et al. Macrophage phagocytosis of biomedical Mg alloy degradation products prepared by electrochemical method. Mater. Sci. Eng. C 75, 1178–1183 (2017).

    CAS  Google Scholar 

  107. Sanchez, A. H. M., Luthringer, B. J. C., Feyerabend, F. & Willumeit, R. Mg and Mg alloys: how comparable are in vitro and in vivo corrosion rates? A review. Acta Biomater. 13, 16–31 (2015).

    CAS  Google Scholar 

  108. Johnston, S., Dargusch, M. & Atrens, A. Building towards a standardised approach to biocorrosion studies: a review of factors influencing Mg corrosion in vitro pertinent to in vivo corrosion. Sci. China Mater. 61, 475–500 (2018).

    CAS  Google Scholar 

  109. Meinel, L. et al. The inflammatory responses to silk films in vitro and in vivo. Biomaterials 26, 147–155 (2005).

    CAS  Google Scholar 

  110. Gross, J. E. et al. An evaluation of SERI surgical scaffold for soft-tissue support and repair in an ovine model of two-stage breast reconstruction. Plast. Reconstr. Surg. 134, 700e–704e (2014).

    CAS  Google Scholar 

  111. Perrone, G. S. et al. The use of silk-based devices for fracture fixation. Nat. Commun. 5, 3385 (2014).

    Google Scholar 

  112. Zhou, J. et al. In vitro and in vivo degradation behavior of aqueous-derived electrospun silk fibroin scaffolds. Polym. Degrad. Stab. 95, 1679–1685 (2010).

    CAS  Google Scholar 

  113. Altman, G. H., Horan, R. L., Collette, A. L., Chen, J. S. & Vanepps, D. Silk fibroin hydrogels and uses thereof. US patent 2011/0008406 A1 (2011).

  114. Jewell, M., Daunch, W., Bengtson, B. & Mortarino, E. The development of SERI® surgical scaffold, an engineered biological scaffold. Ann. NY Acad. Sci. 1358, 44–55 (2015).

    CAS  Google Scholar 

  115. Thurber, A. E., Omenetto, F. G. & Kaplan, D. L. In vivo bioresponses to silk proteins. Biomaterials 71, 145–157 (2015).

    CAS  Google Scholar 

  116. Tsubouchi, K., Nakao, H., Igarashi, Y., Takasu, Y. & Yamada, H. Bombyx mori fibroin enhanced the proliferation of cultured human skin fibroblasts. J. Insect Biotechnol. Sericol. 72, 65–69 (2003).

    CAS  Google Scholar 

  117. Wray, L. S. et al. Effect of processing on silk-based biomaterials: Reproducibility and biocompatibility. J. Biomed. Mater. Res. B Appl. Biomater. 99B, 89–101 (2011).

    CAS  Google Scholar 

  118. Numata, K., Cebe, P. & Kaplan, D. L. Mechanism of enzymatic degradation of beta-sheet crystals. Biomaterials 31, 2926–2933 (2010).

    CAS  Google Scholar 

  119. Lundmark, K., Westermark, G. T., Olsén, A. & Westermark, P. Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice: Cross-seeding as a disease mechanism. Proc. Natl Acad. Sci. USA 102, 6098–6102 (2005).

    CAS  Google Scholar 

  120. Dziki, J. et al. An acellular biologic scaffold treatment for volumetric muscle loss: results of a 13-patient cohort study. NPJ Regen. Med. 1, 16008 (2016).

    Google Scholar 

  121. Dziki, J. L., Sicari, B. M., Wolf, M. T., Cramer, M. C. & Badylak, S. F. Immunomodulation and mobilization of progenitor cells by extracellular matrix bioscaffolds for volumetric muscle loss treatment. Tissue Eng. Part A 22, 1129–1139 (2016).

    CAS  Google Scholar 

  122. Londono, R. & Badylak, S. F. Biologic scaffolds for regenerative medicine: mechanisms of in vivo remodeling. Ann. Biomed. Eng. 43, 577–592 (2015).

    Google Scholar 

  123. Lopresti, S. T. & Brown, B. N. in Host Response to Biomaterials: The Impact of Host Response on Biomaterial Selection (ed. Badylak, S. F.) 53–79 (Academic, 2015).

  124. Sicari, B. M. et al. An acellular biologic scaffold promotes skeletal muscle formation in mice and humans with volumetric muscle loss. Sci. Transl Med. 6, 234ra258 (2014).

    Google Scholar 

  125. Xu, H. et al. Host response to human acellular dermal matrix transplantation in a primate model of abdominal wall repair. Tissue Eng. Part A 14, 2009–2019 (2008).

    CAS  Google Scholar 

  126. Xu, H. et al. A porcine-derived acellular dermal scaffold that supports soft tissue regeneration: removal of terminal galactose-α-(1,3)-galactose and retention of matrix structure. Tissue Eng. Part A 15, 1807–1819 (2009).

    CAS  Google Scholar 

  127. Zhang, J. et al. Perfusion-decellularized skeletal muscle as a three-dimensional scaffold with a vascular network template. Biomaterials 89, 114–126 (2016).

    CAS  Google Scholar 

  128. Badylak, S. F., Valentin, J. E., Ravindra, A. K., McCabe, G. P. & Stewart-Akers, A. M. Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng. Part A 14, 1835–1842 (2008).

    CAS  Google Scholar 

  129. Brown, B. N. et al. Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. Acta Biomater. 8, 978–987 (2012).

    CAS  Google Scholar 

  130. Lloyd, C. M. & Snelgrove, R. J. Type 2 immunity: expanding our view. Sci. Immunol. 3, eaat1604 (2018).

    Google Scholar 

  131. Chan, A. J., Jang, J. C. & Nair, M. G. in The Th2 Type Immune Response in Health and Disease: From Host Defense and Allergy to Metabolic Homeostasis and Beyond (eds Gause, W. C. & Artis, D.) 115–130 (Springer, 2016).

  132. Keane, T. J., Horejs, C.-M. & Stevens, M. M. Scarring vs. functional healing: matrix-based strategies to regulate tissue repair. Adv. Drug Del. Rev. 129, 407–419 (2018).

    CAS  Google Scholar 

  133. Aamodt, J. M. & Grainger, D. W. Extracellular matrix-based biomaterial scaffolds and the host response. Biomaterials 86, 68–82 (2016).

    CAS  Google Scholar 

  134. Morris, A. H., Stamer, D. K. & Kyriakides, T. R. The host response to naturally-derived extracellular matrix biomaterials. Semin. Immunol. 29, 72–91 (2017).

    CAS  Google Scholar 

  135. Morris, A. H., Chang, J. & Kyriakides, T. R. Inadequate processing of decellularized dermal matrix reduces cell viability in vitro and increases apoptosis and acute inflammation in vivo. BioResearch Open Access 5, 177–187 (2016).

    CAS  Google Scholar 

  136. de Castro Brás, L. E., Shurey, S. & Sibbons, P. D. Evaluation of crosslinked and non-crosslinked biologic prostheses for abdominal hernia repair. Hernia 16, 77–89 (2012).

    Google Scholar 

  137. Jones, K. S. Effects of biomaterial-induced inflammation on fibrosis and rejection. Semin. Immunol. 20, 130–136 (2008).

    CAS  Google Scholar 

  138. Kim, M. S. et al. An in vivo study of the host tissue response to subcutaneous implantation of PLGA- and/or porcine small intestinal submucosa-based scaffolds. Biomaterials 28, 5137–5143 (2007).

    CAS  Google Scholar 

  139. Böstman, O. & Pihlajamäki, H. Clinical biocompatibility of biodegradable orthopaedic implants for internal fixation: a review. Biomaterials 21, 2615–2621 (2000).

    Google Scholar 

  140. Sung, H.-J., Meredith, C., Johnson, C. & Galis, Z. S. The effect of scaffold degradation rate on three-dimensional cell growth and angiogenesis. Biomaterials 25, 5735–5742 (2004).

    CAS  Google Scholar 

  141. Böstman, O. M. & Pihlajamäki, H. K. Adverse tissue reactions to bioabsorbable fixation devices. Clin. Orthop. Relat. Res. 371, 216–227 (2000).

    Google Scholar 

  142. Bergsma, J. E., de Bruijn, W. C., Rozema, F. R., Bos, R. R. M. & Boering, G. Late degradation tissue response to poly(l-lactide) bone plates and screws. Biomaterials 16, 25–31 (1995).

    CAS  Google Scholar 

  143. Seino, D., Fukunishi, S. & Yoshiya, S. Late foreign-body reaction to PLLA screws used for fixation of acetabular osteotomy. J. Orthop. Traumatol. 8, 188–191 (2007).

    Google Scholar 

  144. Jeon, H. B., Kang, D. H., Gu, J. H. & Oh, S. A. Delayed foreign body reaction caused by bioabsorbable plates used for maxillofacial fractures. Arch. Plast. Surg. 43, 40–45 (2016).

    Google Scholar 

  145. Gu, X., Zheng, Y., Cheng, Y., Zhong, S. & Xi, T. In vitro corrosion and biocompatibility of binary magnesium alloys. Biomaterials 30, 484–498 (2009).

    CAS  Google Scholar 

  146. Seitz, J.-M., Eifler, R., Bach, Fr.-W. & Maier, H. J. Magnesium degradation products: Effects on tissue and human metabolism. J. Biomed. Mater. Res. A 102, 3744–3753 (2014).

    Google Scholar 

  147. Xiao, C. et al. Indirectly extruded biodegradable Zn-0.05 wt% Mg alloy with improved strength and ductility: In vitro and in vivo studies. J. Mater. Sci. Technol. 34, 1618–1627 (2018).

    Google Scholar 

  148. Ma, J., Zhao, N., Betts, L. & Zhu, D. Bio-adaption between magnesium alloy stent and the blood vessel: a review. J. Mater. Sci. Technol. 32, 815–826 (2016).

    Google Scholar 

  149. Zhang, Y. et al. Implant-derived magnesium induces local neuronal production of CGRP to improve bone-fracture healing in rats. Nat. Med. 22, 1160–1169 (2016).

    CAS  Google Scholar 

  150. Zhao, N. & Zhu, D. Endothelial responses of magnesium and other alloying elements in magnesium-based stent materials. Metallomics 7, 118–128 (2015).

    CAS  Google Scholar 

  151. Kanno, T., Sukegawa, S., Furuki, Y., Nariai, Y. & Sekine, J. Overview of innovative advances in bioresorbable plate systems for oral and maxillofacial surgery. Jpn Dent. Sci. Rev. 54, 127–138 (2018).

    Google Scholar 

  152. Pina, S. & Ferreira, J. M. Bioresorbable plates and screws for clinical applications: a review. J. Healthc. Eng. 3, 243–260 (2012).

    Google Scholar 

  153. Walton, M. & Cotton, N. J. Long-term in vivo degradation of poly-L-lactide (PLLA) in bone. J. Biomater. Appl. 21, 395–411 (2007).

    CAS  Google Scholar 

  154. Ambrose, C. G. & Clanton, T. O. Bioabsorbable implants: review of clinical experience in orthopedic surgery. Ann. Biomed. Eng. 32, 171–177 (2004).

    Google Scholar 

  155. Barber, F. A., Dockery, W. D. & Hrnack, S. A. Long-term degradation of a poly-lactide co-glycolide/β-tricalcium phosphate biocomposite interference screw. Arthroscopy 27, 637–643 (2011).

    Google Scholar 

  156. Costi, J. J., Kelly, A. J., Hearn, T. C. & Martin, D. K. Comparison of torsional strengths of bioabsorbable screws for anterior cruciate ligament reconstruction. Am. J. Sports Med. 29, 575–580 (2001).

    CAS  Google Scholar 

  157. Daculsi, G., Goyenvalle, E., Cognet, R., Aguado, E. & Suokas, E. O. Osteoconductive properties of poly(96L/4D-lactide)/beta-tricalcium phosphate in long term animal model. Biomaterials 32, 3166–3177 (2011).

    CAS  Google Scholar 

  158. Frosch, K. H. et al. Magnetic resonance imaging analysis of the bioabsorbable Milagro™ interference screw for graft fixation in anterior cruciate ligament reconstruction. Strateg. Trauma Limb Reconstr. 4, 73–79 (2009).

    Google Scholar 

  159. Vonhoegen, J., John, D. & Hägermann, C. Osteoconductive resorption characteristics of a novel biocomposite suture anchor material in rotator cuff repair. J. Orthop. Surg. Res. 14, 12 (2019).

    Google Scholar 

  160. Aunoble, S., Clement, D., Frayssinet, P., Harmand, M. F. & Le Huec, J. C. Biological performance of a new β-TCP/PLLA composite material for applications in spine surgery: in vitro and in vivo studies. J. Biomed. Mater. Res. A 78, 416–422 (2006).

    Google Scholar 

  161. Chivot, M. et al. Pull-out strength of four tibial fixation devices used in anterior cruciate ligament reconstruction. Orthop. Traumatol. Surg. Res. 104, 203–207 (2018).

    CAS  Google Scholar 

  162. Kundu, B., Rajkhowa, R., Kundu, S. C. & Wang, X. Silk fibroin biomaterials for tissue regenerations. Adv. Drug Del. Rev. 65, 457–470 (2013).

    CAS  Google Scholar 

  163. Yucel, T., Lovett, M. L. & Kaplan, D. L. Silk-based biomaterials for sustained drug delivery. J. Control. Release 190, 381–397 (2014).

    CAS  Google Scholar 

  164. Koh, L.-D. et al. Structures, mechanical properties and applications of silk fibroin materials. Prog. Polym. Sci. 46, 86–110 (2015).

    CAS  Google Scholar 

  165. Brown, J. E. et al. Injectable silk protein microparticle-based fillers: a novel material for potential use in glottic insufficiency. J. Voice 33, 773–780 (2019).

    Google Scholar 

  166. Marelli, B. et al. Programming function into mechanical forms by directed assembly of silk bulk materials. Proc. Natl Acad. Sci. USA 114, 451–456 (2016).

    Google Scholar 

  167. Li, C. et al. Regenerated silk materials for functionalized silk orthopedic devices by mimicking natural processing. Biomaterials 110, 24–33 (2016).

    CAS  Google Scholar 

  168. Guo, C. et al. Thermoplastic molding of regenerated silk. Preprint at ChemRxiv https://doi.org/10.26434/chemrxiv.8343848 (2019).

  169. MedMarket Diligence. Global dynamics of surgical and interventional cardiovascular procedures, 2015–2022 (2016).

  170. Gori, T. et al. Predictors of stent thrombosis and their implications for clinical practice. Nat. Rev. Cardiol. 16, 243–256 (2019).

    Google Scholar 

  171. Finn, A. V. et al. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation 115, 2435–2441 (2007).

    Google Scholar 

  172. Serruys, P. W., Garcia-Garcia, H. M. & Onuma, Y. From metallic cages to transient bioresorbable scaffolds: change in paradigm of coronary revascularization in the upcoming decade? Eur. Heart J. 33, 16–25 (2011).

    Google Scholar 

  173. Joner, M. et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J. Am. Coll. Cardiol. 48, 193–202 (2006).

    Google Scholar 

  174. Jinnouchi, H. et al. Fully bioresorbable vascular scaffolds: lessons learned and future directions. Nat. Rev. Cardiol. 16, 286–304 (2018).

    Google Scholar 

  175. Wang, P.-J., Ferralis, N., Conway, C., Grossman, J. C. & Edelman, E. R. Strain-induced accelerated asymmetric spatial degradation of polymeric vascular scaffolds. Proc. Natl Acad. Sci. USA 115, 2640–2645 (2018).

    CAS  Google Scholar 

  176. Sharma, U. et al. The development of bioresorbable composite polymeric implants with high mechanical strength. Nat. Mater. 17, 96–103 (2017).

    Google Scholar 

  177. Kang, S. K. et al. Bioresorbable silicon electronic sensors for the brain. Nature 530, 71–76 (2016).

    CAS  Google Scholar 

  178. Boutry, C. M. et al. A sensitive and biodegradable pressure sensor array for cardiovascular monitoring. Adv. Mater. 27, 6954–6961 (2015).

    CAS  Google Scholar 

  179. Yu, K. J. et al. Bioresorbable silicon electronics for transient spatiotemporal mapping of electrical activity from the cerebral cortex. Nat. Mater. 15, 782–791 (2016).

    CAS  Google Scholar 

  180. Hwang, S. W. et al. A physically transient form of silicon electronics. Science 337, 1640–1644 (2012).

    CAS  Google Scholar 

  181. Tao, H. et al. Silk-based resorbable electronic devices for remotely controlled therapy and in vivo infection abatement. Proc. Natl Acad. Sci. USA 111, 17385–17389 (2014).

    CAS  Google Scholar 

  182. Tibbitt, M. W., Rodell, C. B., Burdick, J. A. & Anseth, K. S. Progress in material design for biomedical applications. Proc. Natl Acad. Sci. USA 112, 14444–14451 (2015).

    CAS  Google Scholar 

  183. Kang, S. K. et al. Dissolution chemistry and biocompatibility of silicon- and germanium-based semiconductors for transient electronics. ACS Appl. Mater. Interfaces 7, 9297–9305 (2015).

    CAS  Google Scholar 

  184. Kim, D.-H. et al. Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics. Nat. Mater. 9, 511–517 (2010).

    CAS  Google Scholar 

  185. Hwang, S. W. et al. Materials for bioresorbable radio frequency electronics. Adv. Mater. 25, 3526–3531 (2013).

    CAS  Google Scholar 

  186. Lei, T. et al. Biocompatible and totally disintegrable semiconducting polymer for ultrathin and ultralightweight transient electronics. Proc. Natl Acad. Sci. USA 114, 5107–5112 (2017).

    CAS  Google Scholar 

  187. Huang, X. et al. Biodegradable materials for multilayer transient printed circuit boards. Adv. Mater. 26, 7371–7377 (2014).

    CAS  Google Scholar 

  188. Shou, W. et al. Low-cost manufacturing of bioresorbable conductors by evaporation-condensation-mediated laser printing and sintering of Zn nanoparticles. Adv. Mater. 29, 1700172 (2017).

    Google Scholar 

  189. Acar, H. et al. Study of physically transient insulating materials as a potential platform for transient electronics and bioelectronics. Adv. Funct. Mater. 24, 4135–4143 (2014).

    CAS  Google Scholar 

  190. Jamshidi, R., Çinar, S., Chen, Y., Hashemi, N. & Montazami, R. Transient bioelectronics: Electronic properties of silver microparticle-based circuits on polymeric substrates subjected to mechanical load. J. Polym. Sci. B Polym. Phys. 53, 1603–1610 (2015).

    CAS  Google Scholar 

  191. Boutry, C. M. et al. A stretchable and biodegradable strain and pressure sensor for orthopaedic application. Nat. Electron. 1, 314–321 (2018).

    Google Scholar 

  192. Hwang, S.-W. et al. High-performance biodegradable/transient electronics on biodegradable polymers. Adv. Mater. 26, 3905–3911 (2014).

    CAS  Google Scholar 

  193. Bettinger, C. J. & Bao, Z. Organic thin-film transistors fabricated on resorbable biomaterial substrates. Adv. Mater. 22, 651–655 (2010).

    CAS  Google Scholar 

  194. Chang, J. K. et al. Biodegradable electronic systems in 3d, heterogeneously integrated formats. Adv. Mater. 30, 1704955 (2018).

    Google Scholar 

  195. Hwang, S. W. et al. 25th anniversary article: materials for high-performance biodegradable semiconductor devices. Adv. Mater. 26, 1992–2000 (2014).

    CAS  Google Scholar 

  196. Yin, L. et al. Mechanisms for hydrolysis of silicon nanomembranes as used in bioresorbable electronics. Adv. Mater. 27, 1857–1864 (2015).

    CAS  Google Scholar 

  197. Lee, Y. K. et al. Dissolution of monocrystalline silicon nanomembranes and their use as encapsulation layers and electrical interfaces in water-soluble electronics. ACS Nano 11, 12562–12572 (2017).

    CAS  Google Scholar 

  198. Kang, S. K., Koo, J., Lee, Y. K. & Rogers, J. A. Advanced materials and devices for bioresorbable electronics. Acc. Chem. Res. 51, 988–998 (2018).

    CAS  Google Scholar 

  199. Oldreive, S. Safe intakes of vitamins and minerals: recommendations from the Expert Group on Vitamins and Minerals. Nutr. Bull. 28, 199–202 (2003).

    Google Scholar 

  200. Song, G. & Song, S. A possible biodegradable magnesium implant material. Adv. Eng. Mater. 9, 298–302 (2007).

    CAS  Google Scholar 

  201. Koo, J. et al. Wireless bioresorbable electronic system enables sustained nonpharmacological neuroregenerative therapy. Nat. Med. 24, 1830–1836 (2018).

    CAS  Google Scholar 

  202. Shin, J. et al. Bioresorbable pressure sensors protected with thermally grown silicon dioxide for the monitoring of chronic diseases and healing processes. Nat. Biomed. Eng. 3, 37–46 (2019).

    CAS  Google Scholar 

  203. Vert, M. et al. Terminology for biorelated polymers and applications (IUPAC Recommendations 2012). Pure Appl. Chem. 84, 377–410 (2012).

    CAS  Google Scholar 

  204. Villa, T. & Brianza, S. in Bioresorbable Polymers for Biomedical Applications: From Fundamentals to Translational Medicine (eds Perale, G. & Hilborn, J.) 95–100 (Woodhead, 2017).

  205. Ozdil, D., Wimpenny, I., Aydin, H. M. & Yang, Y. in Science and Principles of Biodegradable and Bioresorbable Medical Polymers (ed. Zhang, X.) 379–414 (Woodhead, 2017).

  206. U.S. Food and Drug Administration. Use of International Standard ISO 10993-1, “Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process” (FDA, 2016).

  207. Guan, A. et al. Medical devices on chips. Nat. Biomed. Eng. 1, 0045 (2017).

    CAS  Google Scholar 

  208. Jannasch, M. et al. An in vitro model mimics the contact of biomaterials to blood components and the reaction of surrounding soft tissue. Acta Biomater. 89, 227–241 (2019).

    CAS  Google Scholar 

  209. Jannasch, M. et al. A comparative multi-parametric in vitro model identifies the power of test conditions to predict the fibrotic tendency of a biomaterial. Sci. Rep. 7, 1689 (2017).

    Google Scholar 

  210. Sharifi, F. et al. A foreign body response-on-a-chip platform. Adv. Healthc. Mater. 8, 1801425 (2019).

    Google Scholar 

  211. Kajahn, J. et al. Artificial extracellular matrices composed of collagen I and high sulfated hyaluronan modulate monocyte to macrophage differentiation under conditions of sterile inflammation. Biomatter 2, 226–273 (2012).

    Google Scholar 

  212. Kou, P. M. et al. Predicting biomaterial property-dendritic cell phenotype relationships from the multivariate analysis of responses to polymethacrylates. Biomaterials 33, 1699–1713 (2012).

    CAS  Google Scholar 

  213. McWhorter, F. Y., Wang, T., Nguyen, P., Chung, T. & Liu, W. F. Modulation of macrophage phenotype by cell shape. Proc. Natl Acad. Sci. USA 110, 17253–17258 (2013).

    CAS  Google Scholar 

  214. Nakamura, K. et al. High, but not low, molecular weight hyaluronan prevents T-cell-mediated liver injury by reducing proinflammatory cytokines in mice. J. Gastroenterol. 39, 346–354 (2004).

    CAS  Google Scholar 

  215. Sridharan, R., Cameron, A. R., Kelly, D. J., Kearney, C. J. & O’Brien, F. J. Biomaterial based modulation of macrophage polarization: a review and suggested design principles. Mater. Today 18, 313–325 (2015).

    CAS  Google Scholar 

  216. Chen, S. et al. Characterization of topographical effects on macrophage behavior in a foreign body response model. Biomaterials 31, 3479–3491 (2010).

    CAS  Google Scholar 

  217. Kamolratanakul, P. et al. Nanogel-based scaffold delivery of prostaglandin E2 receptor–specific agonist in combination with a low dose of growth factor heals critical-size bone defects in mice. Arthritis Rheum. 63, 1021–1033 (2011).

    CAS  Google Scholar 

  218. Lau, T. T. & Wang, D.-A. Stromal cell-derived factor-1 (SDF-1): homing factor for engineered regenerative medicine. Expert. Opin. Biol. Ther. 11, 189–197 (2011).

    CAS  Google Scholar 

  219. Shen, W. et al. The effect of incorporation of exogenous stromal cell-derived factor-1 alpha within a knitted silk-collagen sponge scaffold on tendon regeneration. Biomaterials 31, 7239–7249 (2010).

    CAS  Google Scholar 

  220. Kim, D.-H. & Martin, D. C. Sustained release of dexamethasone from hydrophilic matrices using PLGA nanoparticles for neural drug delivery. Biomaterials 27, 3031–3037 (2006).

    CAS  Google Scholar 

  221. Mercanzini, A. et al. Controlled release nanoparticle-embedded coatings reduce the tissue reaction to neuroprostheses. J. Control. Release 145, 196–202 (2010).

    CAS  Google Scholar 

  222. Chen, W. C. W. et al. Controlled dual delivery of fibroblast growth factor-2 and Interleukin-10 by heparin-based coacervate synergistically enhances ischemic heart repair. Biomaterials 72, 138–151 (2015).

    CAS  Google Scholar 

  223. Mokarram, N., Merchant, A., Mukhatyar, V., Patel, G. & Bellamkonda, R. V. Effect of modulating macrophage phenotype on peripheral nerve repair. Biomaterials 33, 8793–8801 (2012).

    CAS  Google Scholar 

  224. Son, D. et al. Bioresorbable electronic stent integrated with therapeutic nanoparticles for endovascular diseases. ACS Nano 9, 5937–5946 (2015).

    CAS  Google Scholar 

  225. Williams, D. F. The Williams Dictionary of Biomaterials (Liverpool Univ. Press, 1999).

  226. ASTM International. Standard guide for assessment of absorbable polymeric implants (ASTM, 2016).

  227. Wegst, U. G. K., Bai, H., Saiz, E., Tomsia, A. P. & Ritchie, R. O. Bioinspired structural materials. Nat. Mater. 14, 23–26 (2015).

    CAS  Google Scholar 

  228. Drogset, J. O., Straume, L. G., Bjørkmo, I. & Myhr, G. A prospective randomized study of ACL-reconstructions using bone-patellar tendon-bone grafts fixed with bioabsorbable or metal interference screws. Knee Surg. Sports Traumatol. Arthrosc. 19, 753–759 (2011).

    Google Scholar 

  229. Oiwa, H., Ishida, R. & Sudo, K. Sternal closure with reabsorbable pin and cord in pediatric less invasive cardiac surgery. Ann. Thorac. Surg. 78, 358–359 (2004).

    Google Scholar 

  230. Saito, T., Iguchi, A., Sakurai, M. & Tabayashi, K. Biomechanical study of a poly-L-lactide (PLLA) sternal pin in sternal closure after cardiothoracic surgery. Ann. Thorac. Surg. 77, 684–687 (2004).

    Google Scholar 

  231. Tatsumi, A., Kanemitsu, N., Nakamura, T. & Shimizu, Y. Bioabsorbable poly-L-lactide costal coaptation pins and their clinical application in thoracotomy. Ann. Thorac. Surg. 67, 765–768 (1999).

    CAS  Google Scholar 

  232. Jarvela, T. et al. Double-bundle anterior cruciate ligament reconstruction using hamstring autografts and bioabsorbable interference screw fixation: prospective, randomized, clinical study with 2-year results. Am. J. Sports Med. 36, 290–297 (2008).

    Google Scholar 

  233. Eppley, B. L. & Reilly, M. Degradation characteristics of PLLA-PGA bone fixation devices. J. Craniofac. Surg. 8, 116–120 (1997).

    CAS  Google Scholar 

  234. Goldstein, J. A., Quereshy, F. A. & Cohen, A. R. Early experience with biodegradable fixation for congenital pediatric craniofacial surgery. J. Craniofac. Surg. 8, 110–115 (1997).

    CAS  Google Scholar 

  235. Pietrzak, W. S. & Eppley, B. L. Stability of craniofacial PLLA/PGA copolymer bioabsorbable screws. J. Craniofac. Surg. 17, 331–336 (2006).

    Google Scholar 

  236. Bowen, P. K., Drelich, A., Drelich, J. & Goldman, J. Rates of in vivo (arterial) and in vitro biocorrosion for pure magnesium. J. Biomed. Mater. Res. A 103, 341–349 (2015).

    Google Scholar 

  237. Nie, F. L., Zheng, Y. F., Wei, S. C., Hu, C. & Yang, G. In vitro corrosion, cytotoxicity and hemocompatibility of bulk nanocrystalline pure iron. Biomed. Mater. 5, 065015 (2010).

    CAS  Google Scholar 

  238. Wang, H. & Shi, Z. In vitro biodegradation behavior of magnesium and magnesium alloy. J. Biomed. Mater. Res. B Appl. Biomater. 98, 203–209 (2011).

    Google Scholar 

  239. Fellman, M. Researchers demonstrate first example of a bioresorbable electronic medicine. McCormick School Engineer. Northwestern Univ. https://www.mccormick.northwestern.edu/news/articles/2018/10/researchers-demonstrate-first-example-of-a-bioresorbable-electronic-medicine.html (2018).

  240. Kerecman Myers, D. et al. From in vivo to in vitro: the medical device testing paradigm shift. ALTEX 34, 479–500 (2017).

    Google Scholar 

Download references

Acknowledgements

We thank the NIH (R01AR068048, 5P41EB002520) and Stepping Strong Foundation, Brigham and Women's Hospital (A.N.) for support of this work. We also thank our many past students who have contributed to some of the foundations discussed here, as well as our many collaborators over the years.

Author information

Authors and Affiliations

Authors

Contributions

C.L., C.G., V.F. and D.K. wrote the manuscript. All authors made substantial contributions to the discussion of the content and reviewed and edited the manuscript before submission.

Corresponding authors

Correspondence to Chunmei Li or David L. Kaplan.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, C., Guo, C., Fitzpatrick, V. et al. Design of biodegradable, implantable devices towards clinical translation. Nat Rev Mater 5, 61–81 (2020). https://doi.org/10.1038/s41578-019-0150-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41578-019-0150-z

This article is cited by

Search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research