Pathology and Histopathology Evaluations of Biomaterials and Medical Devices

  • JoAnn C. L. SchuhEmail author


This chapter will focus on pathology- and histopathology-based study interactions that will optimize the study design, tissue collection and preparation, and evaluation, interpretation, and documentation of biologic responses to biomaterials and finished medical devices. Much of provided information is also applicable to pathology and histopathology evaluations of combination products (device and pharmaceutical or biologics) and regenerative medicine products that include engineered or polymer scaffolds. The reader should be familiar with and consult the most recent ISO and country-specific regulatory standards and reviews to ensure regulatory compliance with the pathology components of any study.


2016 Biofilms Biopsy samples Carcinogenicity studies Causality Determination of complete biodegradation FDA Foreign body response (FBR) Histopathology evaluations Imaging techniques Immunohistochemistry Immunotoxicity Infections International Harmonization of Nomenclature and Diagnostic (INHAND) Criteria Local and systemic immune reactions Local implantation sites Macroscopic anatomical pathology Modifiers of tissue responses Nomenclature International Organization for Standardization Quantitative (objective) morphometry Resin embedment Risk assessment plan Standardization for Exchange of Nonclinical Data (SEND) Tissue lists 


  1. Abbondanzo, S. L., Young, V. L., Wei, M. Q., & Miller, F. W. (1999). Silicone gel-filled breast and testicular implant capsules: A histologic and immunophenotypic study. Modern Pathology, 12, 706–713.PubMedGoogle Scholar
  2. Adhikari, R., et al. (2008). Biodegradable injectable polyurethanes: Synthesis and evaluation for orthopaedic applications. Biomaterials, 29, 3762–3770.PubMedCrossRefGoogle Scholar
  3. Albl, B., et al. (2016). Tissue sampling guides for porcine biomedical models. Toxicologic Pathology, 44, 414–420.PubMedCrossRefGoogle Scholar
  4. Altman, D., Rogers, R. G., Yin, L., Tamussino, K., Ye, W., & Iglesia, C. B. (2018). Cancer risk after Midurethral Sling surgery using polypropylene mesh. Obstetrics and Gynecology, 131, 469–474. Scholar
  5. Alves, A., Wanket, L., & Metz, A. (2019). Current considerations in medical device pathology. In J.-P Boutrand (Ed.), Biocompatibility and Performance of Medical Devices (2nd ed. pp. 489–543). Cambridge: Elsevier.Google Scholar
  6. Amini, A. R., Wallace, J. S., & Nukavarapu, S. P. (2011). Short-term and long-term effects of orthopedic biodegradable implants. Journal of Long-Term Effects of Medical Implants, 21, 93–122.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Anderson, J. M., Rodriguez, A., & Chang, D. T. (2008). Foreign body reaction to biomaterials. Seminars in Immunology, 20, 86–100.PubMedCrossRefGoogle Scholar
  8. Ang, H. Y., Bulluck, H., Wong, P., Venkatraman, S. S., Huang, Y., & Foin, N. (2017). Bioresorbable stents: Current and upcoming bioresorbable technologies. International Journal of Cardiology, 228, 931–939.PubMedCrossRefGoogle Scholar
  9. Appel, A. A., Anastasio, M. A., Larson, J. C., & Brey, E. M. (2013). Imaging challenges in biomaterials and tissue engineering. Biomaterials, 34, 6615–6630. Scholar
  10. Athanasou, N. (2016). The pathobiology and pathology of aseptic implant failure. Bone & Joint Research, 5, 162–168.CrossRefGoogle Scholar
  11. Badylak, S. F. (2015). Host response to biomaterials: The impact of host response on biomaterial selection (1st ed.). San Diego: Academic Press.Google Scholar
  12. Baklanov, D. V., Peters, K. G., Seidel, A. L., Taylor, D. A., & Annex, B. H. (2003). Neovascularization in intimal hyperplasia is associated with vein graft failure after coronary artery bypass surgery. Vascular Medicine, 8, 163–167.PubMedCrossRefGoogle Scholar
  13. Barbolt, T. A., Odin, M., Léger, M., Kangas, L., Holste, J., & Liu, S. H. (2001). Biocompatibility evaluation of dura mater substitutes in an animal model. Neurological Research, 23, 813–820. Scholar
  14. Batniji, R. K., Hutchison, J. L., Dahiya, R., Lam, S. L., & Williams, E. F. (2002). Tissue response to expanded polytetrafluoroethylene and silicone implants in a rabbit model. Archives of Facial Plastic Surgery, 4, 111–113.PubMedCrossRefGoogle Scholar
  15. Bauer, T. W. (1996). Identification of orthopaedic wear debris. Journal of Bone and Joint Surgery, 79, 479–483.CrossRefGoogle Scholar
  16. Becerra, S. C., Roy, D. C., Sanchez, C. J., Christy, R. J., & Burmeister, D. M. (2016). An optimized staining technique for the detection of gram positive and gram negative bacteria within tissue. BMC Research Notes, 9, 216. Scholar
  17. Bergknut, N., et al. (2013). Intervertebral disc disease in dogs–Part 1: A new histological grading scheme for classification of intervertebral disc degeneration in dogs. Veterinary Journal, 195, 156–163.CrossRefGoogle Scholar
  18. Bergsma, J., De Bruijn, W., Rozema, F., Bos, R., & Boering, G. (1995a). Late degradation tissue response to poly (L-lactide) bone plates and screws. Biomaterials, 16, 25–31.PubMedCrossRefGoogle Scholar
  19. Bergsma, J. E., Rozema, F., Bos, R., Boering, G., de Bruijn, W., & Pennings, A. (1995b). In vivo degradation and biocompatibility study of in vitro pre-degraded as-polymerized polylactide particles. Biomaterials, 16, 267–274.PubMedCrossRefGoogle Scholar
  20. Bischoff, F., & Bryson, G. (1964). Carcinogenesis through solid state surfaces. Progress in Experimental Tumor Research, 5, 85–133.PubMedCrossRefGoogle Scholar
  21. Blanchard, K. T., et al. (1999). Transponder induced sarcoma in the Heterozygous p53+/− mouse. Toxicologic Pathology, 27, 519–527.PubMedCrossRefGoogle Scholar
  22. Bölgen, N., Menceloğlu, Y. Z., Acatay, K., Vargel, I., & Pişkin, E. (2005). In vitro and in vivo degradation of non-woven materials made of poly (ε-caprolactone) nanofibers prepared by electrospinning under different conditions. Journal of Biomaterials Science. Polymer Edition, 16, 1537–1555.PubMedCrossRefGoogle Scholar
  23. Boyce, J. T., Boyce, R. W., & Gundersen, H. J. (2010). Choice of morphometric methods and consequences in the regulatory environment. Toxicologic Pathology, 38, 1128–1133.PubMedCrossRefGoogle Scholar
  24. Brand, K. G., Buoen, L. C., & Brand, I. (1975a). Foreign-body tumorigenesis induced by glass and smooth and rough plastic. Comparative study of preneoplastic events. Journal of the National Cancer Institute, 55, 319–322.PubMedGoogle Scholar
  25. Brand, K. G., Buoen, L. C., Johnson, K. H., & Brand, I. (1975b). Etiological factors, stages, and the role of the foreign body in foreign body tumorigenesis a review. Cancer Research, 35, 279–286.PubMedGoogle Scholar
  26. Brewster, D. H., Stockton, D. L., Reekie, A., Ashcroft, G. P., Howie, C. R., Porter, D. E., & Black, R. J. (2013). Risk of cancer following primary total hip replacement or primary resurfacing arthroplasty of the hip: A retrospective cohort study in Scotland. British Journal of Cancer, 108, 1883–1890. Scholar
  27. Brown, B. N., Mani, D., Nolfi, M. A. L., Liang, R., Abramowitch, S., & Moalli, P. A. (2015). Characterization of the host inflammatory response following implantation of prolapse mesh in rhesus macaque. American Journal of Obstetrics and Gynecology, 213, 668.e661–668.e610. Scholar
  28. Budras, K. D., McCarthy, P. H., Fricke, W., Richter, R., Horowitz, A., & Berg, R. (2007). Anatomy of the dog: An illustrated text. Hanover: Schlütersche Verlagsgesellschaft mbH &.Google Scholar
  29. Busscher, H. J., et al. (2012). Biomaterial-associated infection: Locating the finish line in the race for the surface. Science Translational Medicine, 4, 153rv110–153rv110.CrossRefGoogle Scholar
  30. Callis, G., Sterchi, D., & National Society for H. (2002). Animal processing manual. Bowie: National Society for Histotechnology.Google Scholar
  31. Caropreso, S., Bondioli, L., Capannolo, D., Cerroni, L., Macchiarelli, R., & Condo, S. (2000). Thin sections for hard tissue histology: A new procedure. Journal of Microscopy, 199, 244–247.PubMedCrossRefGoogle Scholar
  32. Carter, R. L., & Roe, F. J. (1969). Induction of sarcomas in rats by solid and fragmented polyethylene: Experimental observations and clinical implications. British Journal of Cancer, 23, 401–407.PubMedPubMedCentralCrossRefGoogle Scholar
  33. Chandra, S. A., et al. (2015). Dermal toxicity studies: Factors impacting study interpretation and outcome. Toxicologic Pathology, 43, 474–481. Scholar
  34. Chen, Q., & Thouas, G. A. (2015). Metallic implant biomaterials. Materials Science & Engineering R: Reports, 87, 1–57.CrossRefGoogle Scholar
  35. Cheville, N. F., & Stasko, J. (2014). Techniques in Electron microscopy of animal tissue. Veterinary Pathology, 51, 28–41. Scholar
  36. Cook, J. L., Kuroki, K., Visco, D., Pelletier, J. P., Schulz, L., & Lafeber, F. P. J. G. (2010). The OARSI histopathology initiative – Recommendations for histological assessments of osteoarthritis in the dog. Osteoarthritis and Cartilage, 18(Supplement 3), S66–S79. Scholar
  37. Crissman, J. W., et al. (2004). Best practices guideline: Toxicologic histopathology. Toxicologic Pathology, 32, 126–131.PubMedCrossRefGoogle Scholar
  38. Dalu, A., Blaydes, B. S., Lomax, L. G., & Delclos, K. B. (2000). A comparison of the inflammatory response to a polydimethylsiloxane implant in male and female Balb/c mice. Biomaterials, 21, 1947–1957.PubMedCrossRefGoogle Scholar
  39. Datta, S., Malhotra, L., Dickerson, R., Chaffee, S., Sen, C. K., & Roy, S. (2015). Laser capture microdissection: Big data from small samples. Histology and Histopathology, 30, 1255–1269. Scholar
  40. Davies, L. C., Jenkins, S. J., Allen, J. E., & Taylor, P. R. (2013). Tissue-resident macrophages. Nature Immunology, 14, 986–995. Scholar
  41. De Jong, W. H., Bergsma, J. E., Robinson, J. E., & Bos, R. R. (2005). Tissue response to partially in vitro predegraded poly-L-lactide implants. Biomaterials, 26, 1781–1791.PubMedCrossRefGoogle Scholar
  42. DeLustro, F., Condell, R. A., Nguyen, M. A., & McPherson, J. M. (1986). A comparative study of the biologic and immunologic response to medical devices derived from dermal collagen. Journal of Biomedical Materials Research, 20, 109–120. Scholar
  43. DiEgidio, P., Friedman, H. I., Gourdie, R. G., Riley, A. E., Yost, M. J., & Goodwin, R. L. (2014). Biomedical implant capsule formation: Lessons learned and the road ahead. Annals of Plastic Surgery, 73, 451–460.PubMedCrossRefGoogle Scholar
  44. Diller, R. B., Audet, R. G., & Kellar, R. S. (2015). Quantitative histopathology for evaluation of in vivo biocompatibility associated with biomedical implants. In J. S. Potts, A. D. Eberhard, & J. A. K. Wharton (Eds.), Molecular histopathology and tissue biomarkers in drug and diagnostic development (pp. 153–162). New York: Springer. Scholar
  45. Dobrovolskaia, M. A. (2015). Pre-clinical immunotoxicity studies of nanotechnology-formulated drugs: Challenges, considerations and strategy. Journal of Controlled Release : Official Journal of the Controlled Release Society, 220, 571–583. Scholar
  46. Donlan, R. M., & Costerton, J. W. (2002). Biofilms: Survival mechanisms of clinically relevant microorganisms. Clinical Microbiology Reviews, 15, 167–193.PubMedPubMedCentralCrossRefGoogle Scholar
  47. dos Santos, P. L., et al. (2016). Evaluation of bone substitutes for treatment of peri-implant bone defects: Biomechanical, histological, and immunohistochemical analyses in the rabbit tibia. Journal of Periodontal & Implant Science, 46, 176–196.CrossRefGoogle Scholar
  48. Douglass, J. P., Berry, C. R., Thrall, D. E., Malarkey, D. E., & Spaulding, K. A. (2003). Radiographic features of aortic bulb/valve mineralization in 20 dogs. Veterinary Radiology & Ultrasound, 44, 20–27.CrossRefGoogle Scholar
  49. Elmore, S. A. (2006a). Enhanced histopathology of mucosa-associated lymphoid tissue. Toxicologic Pathology, 34, 687–696. Scholar
  50. Elmore, S. A. (2006b). Enhanced histopathology of the lymph nodes. Toxicologic Pathology, 34, 634–647.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Elmore, S. A. (2006c). Enhanced histopathology of the spleen. Toxicologic Pathology, 34, 648–655.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Elmore, S. A. (2006d). Enhanced histopathology of the thymus. Toxicologic Pathology, 34, 656.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Elmore, S. A., et al. (2017). Proceedings of the 2017 National Toxicology Program Satellite Symposium. Toxicologic Pathology, 45, 799–833. Scholar
  54. Evans, H. E., & De Lahunta, A. (2013). Miller's anatomy of the dog (4th ed.). St. Louis: Elsevier Health Sciences.Google Scholar
  55. Everds, N. E., et al. (2013). Interpreting stress responses during routine toxicity studies: A review of the biology, impact, and assessment. Toxicologic Pathology, 41, 560–614. Scholar
  56. Farrah, K., Mierzwinski-Urban, M., & Cimon, K. (2016). Effectiveness of adverse effects search filters: Drugs versus medical devices. Journal of the Medical Library Association: JMLA, 104, 221–225. Scholar
  57. Fellah, B. H., Weiss, P., Gauthier, O., Rouillon, T., Pilet, P., Daculsi, G., & Layrolle, P. (2006). Bone repair using a new injectable self-crosslinkable bone substitute. Journal of Orthopaedic Research, 24, 628–635.PubMedCrossRefGoogle Scholar
  58. Fernandez-Bueno, I., et al. (2015). Safety and biocompatibility of a new high-density polyethylene-based spherical integrated porous orbital implant: An experimental study in rabbits. Journal of Ophthalmology, 2015, 904096.PubMedPubMedCentralCrossRefGoogle Scholar
  59. Frydman, G. H., et al. (2017). Local and systemic changes associated with long-term, percutaneous, static implantation of titanium alloys in rhesus macaques (Macaca mulatta). Comparative Medicine, 67, 165–175.PubMedPubMedCentralGoogle Scholar
  60. Funk, K. A., Hampshire, V. A., & Schuh, J. C. L. (2018). Nonclinical safety evaluation of medical devices. In P. S. Sahota, J. A. Popp, P. Bouchard, J. F. Hardisty, & C. Gopinath (Eds.), Toxicologic pathology: Nonclinical safety assessment (2nd ed.). Boca Raton: CRC Press.Google Scholar
  61. Gad, S. C., & Gad-McDonald, S. (2016). Biomaterials, medical devices, and combination products: Biocompatibility testing and safety assessment. Boca Raton: CRC Press.Google Scholar
  62. Gad, S. C., & Schuh, J. C. L. (2018). Regulatory forum opinion paper: Considerations for toxicologic pathologists evaluating the safety of biomaterials and finished medical devices. Toxicologic Pathology, 46, 366–371. Scholar
  63. Gage, G. J., Kipke, D. R., & Shain, W. (2012). Whole animal perfusion fixation for rodents. Journal of Visualized Experiments : JoVE, 3564.
  64. Ganta, S. R., et al. (2003). Vascularization and tissue infiltration of a biodegradable polyurethane matrix. Journal of Biomedical Materials Research. Part A, 64, 242–248.PubMedPubMedCentralCrossRefGoogle Scholar
  65. Gauthier, B. E., Gervais, F., Hamm, G., O’Shea, D., Piton, A., & Schumacher, V. L. (2019). Toxicologic pathology forum: opinion on integrating innovative digital pathology tools in the regulatory framework. Toxicologic Pathology, 47, 436–443.Google Scholar
  66. Gibon, E., et al. (2017a). The biological response to orthopaedic implants for joint replacement: Part I: Metals. Journal of Biomedical Materials Research. Part B, Applied Biomaterials, 105, 2162–2173.PubMedCrossRefGoogle Scholar
  67. Gibon, E., Córdova, L. A., Lu, L., Lin, T. H., Yao, Z., Hamadouche, M., & Goodman, S. B. (2017b). The biological response to orthopedic implants for joint replacement. II: Polyethylene, ceramics, PMMA, and the foreign body reaction. Journal of Biomedical Materials Research. Part B, Applied Biomaterials, 105, 1685–1691.PubMedCrossRefGoogle Scholar
  68. Goad, M., & Goad, D. (2013). Biomedical materials and devices. In W. M. Haschek, C. G. Rousseaux, M. A. Wallig, B. Bolon, R. Ochoa, & B. Mahler (Eds.), Haschek and Rousseaux's handbook of toxicologic pathology (Vol. 3, 3rd ed., pp. 783–806). San Diego: Elsevier (Academic Press).CrossRefGoogle Scholar
  69. Golder, S., Wright, K., & Rodgers, M. (2014). Failure or success of search strategies to identify adverse effects of medical devices: A feasibility study using a systematic review. Systematic Reviews, 3, 113–113. Scholar
  70. Gorbet, M. B., & Sefton, M. V. (2004). Biomaterial-associated thrombosis: Roles of coagulation factors, complement, platelets and leukocytes. Biomaterials, 25, 5681–5703. Scholar
  71. Greaves, P., et al. (2013). Proliferative and non-proliferative lesions of the rat and mouse soft tissue, skeletal muscle and mesothelium. Journal of Toxicologic Pathology, 26, 1S–26S. Scholar
  72. Greenwood, J. E., & Dearman, B. L. (2012). Split skin graft application over an integrating, biodegradable temporizing polymer matrix: Immediate and delayed. Journal of Burn Care & Research, 33, 7–19.CrossRefGoogle Scholar
  73. Grossman, J. D., & Getty, R. (1975a). Sisson and Grossman's the anatomy of the domestic animals: Equine, ruminant (Vol. I, 5th ed.). Philadelphia: Saunders.Google Scholar
  74. Grossman, J. D., & Getty, R. (1975b). Sisson and Grossman's the anatomy of the domestic animals: Porcine, carnivore, Aves (Vol. 2, 5th ed.). Philadelphia: Saunders.Google Scholar
  75. Gundersen, H. J. G., Mirabile, R., Brown, D., & Boyce, R. W. (2013). Stereological principles and sampling procedures for toxicologic pathologists. In W. M. Haschek, C. G. Rousseaux, & M. A. Wallig (Eds.), Haschek and Rousseaux's handbook of toxicologic pathology (Vol. 1, 3rd ed., pp. 215–286). Boston: Academic Press. Scholar
  76. Handel, N. (2006). Long-term safety and efficacy of polyurethane foam-covered breast implants. Aesthetic Surgery Journal, 26, 265–274.PubMedCrossRefGoogle Scholar
  77. Hansen, T., et al. (2002). New aspects in the histological examination of polyethylene wear particles in failed total joint replacements. Acta Histochemica, 104, 263–269. Scholar
  78. Harrell, M. I., Iritani, B. M., & Ruddell, A. (2008). Lymph node mapping in the mouse. Journal of Immunological Methods, 332, 170–174.PubMedCrossRefGoogle Scholar
  79. Hassler, C., Boretius, T., & Stieglitz, T. (2011). Polymers for neural implants. Journal of Polymer Science Part B: Polymer Physics, 49, 18–33. Scholar
  80. Heredia, J. E., et al. (2013). Type 2 innate signals stimulate fibro/adipogenic progenitors to facilitate muscle regeneration. Cell, 153, 376–388.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Honari, G., Ellis, S. G., Wilkoff, B. L., Aronica, M. A., Svensson, L. G., & Taylor, J. S. (2008). Hypersensitivity reactions associated with endovascular devices. Contact Dermatitis, 59, 7–22.PubMedCrossRefGoogle Scholar
  82. Hook, A. L., et al. (2012). Combinatorial discovery of polymers resistant to bacterial attachment. Nature Biotechnology, 30, 868.PubMedPubMedCentralCrossRefGoogle Scholar
  83. Hooper, K. A., Macon, N. D., & Kohn, J. (1998). Comparative histological evaluation of new tyrosine-derived polymers and poly (L-lactic acid) as a function of polymer degradation. Journal of Biomedical Materials Research. Part A, 41, 443–454.CrossRefGoogle Scholar
  84. Horne, J., Bateman, A. C., Carr, N. J., & Ryder, I. (2014). Lymph node revealing solutions in colorectal cancer: Should they be used routinely? Journal of Clinical Pathology, 67, 383–388. Scholar
  85. Hu, W.-J., Eaton, J. W., Ugarova, T. P., & Tang, L. (2001). Molecular basis of biomaterial-mediated foreign body reactions. Blood, 98, 1231–1238.PubMedCrossRefGoogle Scholar
  86. Iezzi, G., et al. (2014). Peri-implant bone tissues around retrieved human implants after time periods longer than 5 years: A retrospective histologic and histomorphometric evaluation of 8 cases. Odontology, 102, 116–121.PubMedCrossRefGoogle Scholar
  87. Ikarashi, Y., et al. (1992). Comparative studies by cell culture and in vivo implantation test on the toxicity of natural rubber latex materials. Journal of Biomedical Materials Research. Part A, 26, 339–356.CrossRefGoogle Scholar
  88. Institute of Medicine. (1999). Safety of silicone breast implants. Washington, DC: The National Academies Press. Scholar
  89. International Council for Harmonisation. (1995). S1A need for carcinogenicity studies of pharmaceuticals.Google Scholar
  90. International Organization for Standardization. (2009). ISO 10993-1: 2009/Cor 1:2010. Part 1: Evaluation and testing within a risk management process. Geneva.Google Scholar
  91. International Organization for Standardization. (2014). ISO 10993-3:2014 tests for genotoxicity, carcinogenicity and reproductive toxicity. Geneva.Google Scholar
  92. International Organization for Standardization. (2016). ISO 10993-6:2016. Part 6: Tests for local effects after implantation. Geneva.Google Scholar
  93. International Organization for Standardization. (2017a). ISO 10993-4: 2017. Part 4: Selection of tests for interactions with blood. Geneva.Google Scholar
  94. International Organization for Standardization. (2017b). ISO 10993-11:2017. Part 11: Tests for systemic toxicity. Geneva.Google Scholar
  95. International Organization for Standardization. (2017c). ISO 10993-16: 2017. Part 16: Toxicokinetic study design for degradation products and leachables. Geneva.Google Scholar
  96. Ionita, C. N., et al. (2009). The asymmetric vascular stent: Efficacy in a rabbit aneurysm model. Stroke, 40, 959–965. Scholar
  97. Ito, R., & Suami, H. (2015). Lymphatic territories (lymphosomes) in swine: an animal model for future lymphatic research. Plastic and Reconstructive Surgery, 136, 297–304.Google Scholar
  98. Jaafar, I. H., LeBlon, C. E., Wei, M.-T., Ou-Yang, D., Coulter, J. P., & Jedlicka, S. S. (2011). Improving fluorescence imaging of biological cells on biomedical polymers. Acta Biomaterialia, 7, 1588–1598. Scholar
  99. Jessen, S. L., et al. (2018). Method for preclinical pathology evaluation and analysis of cardiovascular implantable electronic device implant sites. Cardiovascular Pathology, 36, 44–52.PubMedCrossRefGoogle Scholar
  100. Jones, K. (2015). Fibrotic response to biomaterials and all associated sequence of fibrosis. In S. F. Badylak (Ed.), Host response to biomaterials (pp. 189–237). Oxford, UK: Academic Press. Scholar
  101. Kalimo, K., Räsänen, L., Aho, H., Mäki, J., Mustikkamki, U. P., & Rantala, I. (1996). Persistent cutaneous pseudolymphoma after intradermal gold injection. Journal of Cutaneous Pathology, 23, 328–334.PubMedCrossRefGoogle Scholar
  102. Kaminski, E. J., Oglesby, R. J., Wood, N. K., & Sandrik, J. (1968). The behavior of biological materials at different sites of implantation. Journal of Biomedical Materials Research, 2, 81–88.PubMedCrossRefGoogle Scholar
  103. Kariyawasam, H. H., & Robinson, D. S. (2006). The eosinophil: The cell and its weapons, the cytokines, its locations. Seminars in Respiratory and Critical Care Medicine, 27, 117–127. Scholar
  104. Keel, S. B., Jaffe, K. A., Nielsen, G. P., & Rosenberg, A. E. (2001). Orthopaedic implant-related sarcoma: A study of twelve cases. Modern Pathology, 14, 969–977.PubMedCrossRefGoogle Scholar
  105. Kesler, C. T., Liao, S., Munn, L. L., & Padera, T. P. (2013). Lymphatic vessels in health and disease. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 3, 111–124.Google Scholar
  106. Kirkpatrick, C. J., et al. (2000). Biomaterial-induced sarcoma : A novel model to study preneoplastic change. The American Journal of Pathology, 156, 1455–1467.PubMedPubMedCentralCrossRefGoogle Scholar
  107. Kittel, B., et al. (2004). Revised guides for organ sampling and trimming in rats and mice–Part 2: A joint publication of the RITA and NACAD groups. Experimental and Toxicologic Pathology, 55, 413–431.PubMedCrossRefGoogle Scholar
  108. Klopfleisch, R., & Jung, F. (2017). The pathology of the foreign body reaction against biomaterials. Journal of Biomedical Materials Research. Part A, 105, 927–940. Scholar
  109. Knoblaugh, S. E., & Randolph-Habecker, J. (2017). Necropsy and histology. In P. M. Treuting, S. M. Dintzis, & K. S. Montine (Eds.), Comparative anatomy and histology: A mouse, rat, and human atlas (2nd ed., pp. 23–51). San Diego: Elsevier.Google Scholar
  110. Konttinen, Y. T., Pajarinen, J., Takakubo, Y., Gallo, J., Nich, C., Takagi, M., & Goodman, S. B. (2014). Macrophage polarization and activation in response to implant debris: Influence by “particle disease” and “ion disease”. Journal of Long-Term Effects of Medical Implants, 24, 267–281.PubMedPubMedCentralCrossRefGoogle Scholar
  111. Kraus, T., Fischerauer, S. F., Hänzi, A. C., Uggowitzer, P. J., Löffler, J. F., & Weinberg, A. M. (2012). Magnesium alloys for temporary implants in osteosynthesis: In vivo studies of their degradation and interaction with bone. Acta Biomaterialia, 8, 1230–1238.PubMedCrossRefGoogle Scholar
  112. Kraus, V. B., Huebner, J. L., DeGroot, J., & Bendele, A. (2010). The OARSI histopathology initiative – Recommendations for histological assessments of osteoarthritis in the Guinea pig. Osteoarthritis and Cartilage, 18(Supplement 3), S35–S52. Scholar
  113. Krenn, V., et al. (2014). Revised histopathological consensus classification of joint implant related pathology. Pathology, Research and Practice, 210, 779–786. Scholar
  114. Krenn, V., & Perino, G. (2017). Histological diagnosis of implant-associated pathologies. Clinical management of joint arthroplasty. Berlin: Springer.CrossRefGoogle Scholar
  115. Latendresse, J. R., Warbrittion, A. R., Jonassen, H., & Creasy, D. M. (2002). Fixation of testes and eyes using a modified Davidson's fluid: Comparison with Bouin's fluid and conventional Davidson's fluid. Toxicologic Pathology, 30, 524–533.PubMedCrossRefGoogle Scholar
  116. Lee, J. M., & Kim, Y. J. (2015). Foreign body granulomas after the use of dermal fillers: Pathophysiology, clinical appearance, histologic features, and treatment. Archives of Plastic Surgery, 42, 232–239. Scholar
  117. Leigh Perkins, L. E. (2010). Preclinical models of restenosis and their application in the evaluation of drug-eluting stent systems. Veterinary Pathology, 47, 58–76. Scholar
  118. Lemperle, G., Morhenn, V. B., Pestonjamasp, V., & Gallo, R. L. (2004). Migration studies and histology of injectable microspheres of different sizes in mice. Plastic and Reconstructive Surgery, 113, 1380–1390.PubMedCrossRefGoogle Scholar
  119. Lie, K. I., Jaeger, G., Nordstoga, K., & Moe, L. (2011). Inflammatory response to therapeutic gold bead implantation in canine hipjoint osteoarthritis. Veterinary Pathology, 48, 1118–1124.PubMedCrossRefGoogle Scholar
  120. Loch-Wilkinson, A., et al. (2017). Breast implant–associated anaplastic large cell lymphoma in Australia and New Zealand: High-surface-area textured implants are associated with increased risk. Plastic and Reconstructive Surgery, 140, 645–654.PubMedCrossRefGoogle Scholar
  121. Long, P. H. (2008). Medical devices in orthopedic applications. Toxicologic Pathology, 36, 85–91. Scholar
  122. Major, M. R., Wong, V. W., Nelson, E. R., Longaker, M. T., & Gurtner, G. C. (2015). The foreign body response: At the interface of surgery and bioengineering. Plastic and Reconstructive Surgery, 135, 1489–1498.PubMedCrossRefGoogle Scholar
  123. Malik, N., et al. (1998). Intravascular stents: A new technique for tissue processing for histology, immunohistochemistry, and transmission electron microscopy. Heart, 80, 509.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Markwardt, N. T., Stokol, J., & Rennaker, R. L. (2013). Sub-meninges implantation reduces immune response to neural implants. Journal of Neuroscience Methods, 214, 119–125. Scholar
  125. Masuda, K., et al. (2005). A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: Correlation between the degree of disc injury and radiological and histological appearances of disc degeneration. Spine, 30, 5–14.PubMedCrossRefGoogle Scholar
  126. Mathiesen, E. B., Ahlbom, A., Bermann, G., & Lindgren, J. (1995). Total hip replacement and cancer. A Cohort Study Bone & Joint Journal, 77, 345–350.Google Scholar
  127. Maul, T. M., et al. (2011). Pre-clinical implants of the Levitronix PediVAS(®) pediatric ventricular assist device – strategy for regulatory approval. Cardiovascular Engineering and Technology, 2, 263–275. Scholar
  128. McGregor, D. B., Baan, R. A., Partensky, C., Rice, J. M., & Wilbourn, J. D. (2000). Evaluation of the carcinogenic risks to humans associated with surgical implants and other foreign bodies; a report of an IARC monographs programme meeting. European Journal of Cancer, 36, 307–313. Scholar
  129. McInnes, E. (2005). Artefacts in histopathology. Comparative Clinical Pathology, 13, 100–108.CrossRefGoogle Scholar
  130. McLaughlin, J. K., Lipworth, L., Murphy, D. K., & Walker, P. S. (2007). The safety of silicone gel-filled breast implants: A review of the epidemiologic evidence. Annals of Plastic Surgery, 59, 569–580.PubMedCrossRefGoogle Scholar
  131. Meng, H.-W., Chien, E. Y., & Chien, H.-H. (2016). Dental implant bioactive surface modifications and their effects on osseointegration: A review. Biomarker Research, 4, 24.PubMedPubMedCentralCrossRefGoogle Scholar
  132. Milde, R., et al. (2015). Multinucleated Giant cells are specialized for complement-mediated phagocytosis and large target destruction. Cell Reports, 13, 1937–1948. Scholar
  133. Moalli, P., Brown, B., Reitman, M. T. F., & Nager, C. W. (2014). Polypropylene mesh: Evidence for lack of carcinogenicity. International Urogynecology Journal, 25, 573–576. Scholar
  134. Moizhess, T. G. (2008). Carcinogenesis induced by foreign bodies. Biochemistry (Mosc), 73, 763–775.CrossRefGoogle Scholar
  135. Monteiro, D. R., Gorup, L. F., Takamiya, A. S., Ruvollo-Filho, A. C., ERd, C., & Barbosa, D. B. (2009). The growing importance of materials that prevent microbial adhesion: Antimicrobial effect of medical devices containing silver. International Journal of Antimicrobial Agents, 34, 103–110. Scholar
  136. Morais, J. M., Papadimitrakopoulos, F., & Burgess, D. J. (2010). Biomaterials/tissue interactions: Possible solutions to overcome foreign body response. The AAPS Journal, 12, 188–196.PubMedPubMedCentralCrossRefGoogle Scholar
  137. Morawietz, G., et al. (2004). Revised guides for organ sampling and trimming in rats and mice–Part 3: A joint publication of the RITA and NACAD groups. Experimental and Toxicologic Pathology, 55, 433–449.PubMedCrossRefGoogle Scholar
  138. Morawietz, L., et al. (2006). Proposal for a histopathological consensus classification of the periprosthetic interface membrane. Journal of Clinical Pathology, 59, 591–597. Scholar
  139. Morton, D., et al. (2010). Recommendations for pathology peer review. Toxicologic Pathology, 38, 1118–1127.PubMedCrossRefGoogle Scholar
  140. Moya, J. S., et al. (2016). Histological response of soda-lime glass-ceramic bactericidal rods implanted in the jaws of beagle dogs. Scientific Reports, 6, 31478. Scholar
  141. Muhamed, J., Revi, D., Rajan, A., Geetha, S., & Anilkumar, T. V. (2015). Biocompatibility and immunophenotypic characterization of a Porcine Cholecyst–derived Scaffold implanted in rats. Toxicologic Pathology, 43, 536–545. Scholar
  142. Nam, S. Y., Ricles, L. M., Suggs, L. J., & Emelianov, S. Y. (2015). Imaging strategies for tissue engineering applications. Tissue Engineering Part B, Reviews, 21, 88–102. Scholar
  143. Neef, N., Nikula, K. J., Francke-Carroll, S., & Boone, L. (2012). Regulatory forum opinion piece: Blind reading of histopathology slides in general toxicology studies∗. Toxicologic Pathology, 40, 697–699. Scholar
  144. Nich, C., & Goodman, S. B. (2014). The role of macrophages in the biological reaction to wear debris from joint replacements. Journal of Long-Term Effects of Medical Implants, 24, 259–265.PubMedPubMedCentralCrossRefGoogle Scholar
  145. Nikula, K. J., & Funk, K. (2016). Regulatory forum opinion piece: An experienced pathologist should be present at necropsy for novel medical device studies. Toxicologic Pathology, 44, 9–11. Scholar
  146. Nyska, A., Schiffenbauer, Y. S., Brami, C. T., Maronpot, R. R., & Ramot, Y. (2014). Histopathology of biodegradable polymers: Challenges in interpretation and the use of a novel compact MRI for biocompatibility evaluation. Polymers for Advanced Technologies, 25, 461–467. Scholar
  147. Oppenheimer, B. S., Oppenheimer, E. T., Danishefsky, I., Stout, A. P., & Eirich, F. R. (1955). Further studies of polymers as carcinogenic agents in animals. Cancer Research, 15, 333–340.PubMedGoogle Scholar
  148. Orenstein, S. B., Saberski, E. R., Kreutzer, D. L., & Novitsky, Y. W. (2012). Comparative analysis of histopathologic effects of synthetic meshes based on material, weight, and pore size in mice. The Journal of Surgical Research, 176, 423–429.PubMedCrossRefGoogle Scholar
  149. Pagán, A. J., & Ramakrishnan, L. (2018). The formation and function of granulomas. Annual Review of Immunology, 36. Scholar
  150. Pearce, M. S., et al. (2012). Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: A retrospective cohort study. The Lancet, 380, 499–505.CrossRefGoogle Scholar
  151. Perkins, R. B., Handal-Orefice, R., Hanchate, A. D., Lin, M., & Paasche-Orlow, M. K. (2016). Risk of undetected cancer at the time of laparoscopic supracervical hysterectomy and laparoscopic myomectomy: Implications for the use of power morcellation. Womens Health Issues, 26, 21–26.PubMedCrossRefGoogle Scholar
  152. Phillips, P. L., Wolcott, R. D., Cowan, L. J., & Schultz, G. S. (2016). Biofilms in wounds and wound dressing. In Wound Healing Biomaterials-Volume 2: Functional Biomaterials (55–78). Philidelphia: Elsevier.Google Scholar
  153. Pierce, L. M., Rao, A., Baumann, S. S., Glassberg, J. E., Kuehl, T. J., & Muir, T. W. (2009). Long-term histologic response to synthetic and biologic graft materials implanted in the vagina and abdomen of a rabbit model. American Journal of Obstetrics and Gynecology, 200, 546.e541– 546.e548. Scholar
  154. Pinchuk, L. (1995). A review of the biostability and carcinogenicity of polyurethanes in medicine and the new generation of biostable polyurethanes. Journal of Biomaterials Science. Polymer Edition, 6, 225–267.CrossRefGoogle Scholar
  155. Pizzoferrato, A., Savarino, L., Stea, S., & Tarabusi, C. (1988). Results of histological grading on 100 cases of hip prosthesis failure. Biomaterials, 9, 314–318.PubMedCrossRefGoogle Scholar
  156. Popesko, P., & Getty, R. (1971). Atlas of topographical anatomy of the domestic animals (Vol. I-III vol I-III).Google Scholar
  157. Popesko, P., Rajtová, V., & Horak, J. (1990). A colour atlas of the anatomy of small laboratory animals: Rat, mouse, hamster (Vol. 2). London: Wolfe Publishing Ltd.Google Scholar
  158. Popesko, P., Rajtová, V., & Horak, J. (1992). A colour atlas of the anatomy of small laboratory animals: Rabbit, Guinea pig (Vol. 1). London: Wolfe Publishing Ltd.Google Scholar
  159. Ramot, Y., et al. (2015a). Long-term local and systemic safety of poly (l-lactide-co-epsilon-caprolactone) after subcutaneous and intra-articular implantation in rats. Toxicologic Pathology, 43, 1127–1140.PubMedCrossRefGoogle Scholar
  160. Ramot, Y., Rousselle, S. D., Yellin, N., Willenz, U., Sabag, I., Avner, A., & Nyska, A. (2016). Biocompatibility and systemic safety of a novel implantable annuloplasty ring for the treatment of mitral regurgitation in a minipig model. Toxicologic Pathology, 44, 655–662. Scholar
  161. Ramot, Y., et al. (2015b). Interspecies differences in reaction to a biodegradable subcutaneous tissue filler: Severe inflammatory granulomatous reaction in the Sinclair minipig. Toxicologic Pathology, 43, 267–271. Scholar
  162. Ratner, B. D., Hoffman, A. S., Schoen, F. J., & Lemons, J. E. (2013). Biomaterials science: An introduction to materials in medicine (3rd ed.). Canada: Academic Press (Elsevier).Google Scholar
  163. Ren, P.-G., Irani, A., Huang, Z., Ma, T., Biswal, S., & Goodman, S. B. (2011). Continuous infusion of UHMWPE particles induces increased bone macrophages and osteolysis. Clinical Orthopaedics and Related Research, 469, 113–122. Scholar
  164. Rentsch, C., Schneiders, W., Manthey, S., Rentsch, B., & Rammelt, S. (2014). Comprehensive histological evaluation of bone implants. Biomatter, 4, e27993. Scholar
  165. Ricciardi, B. F., et al. (2016). Histopathological characterization of corrosion product associated adverse local tissue reaction in hip implants: A study of 285 cases. BMC Clinical Pathology, 16, 3. Scholar
  166. Rigdon, R. (1973). Local reaction to polyurethane—A comparative study in the mouse, rat, and rabbit. Journal of Biomedical Materials Research, 7, 79–93.PubMedCrossRefGoogle Scholar
  167. Ripamonti, U. (1996). Osteoinduction in porous hydroxyapatite implanted in heterotopic sites of different animal models. Biomaterials, 17, 31–35.PubMedCrossRefGoogle Scholar
  168. Rismanchian, M., Movahedian, B., Khalighinejad, N., Badrian, H., Mohammad Razavi, S., & Nekouie, A. (2012). Comparative evaluation of two types of immediately loaded implants using biomechanical and histomorphometric tests: An animal case study. ISRN Dentistry, 2012, 328945. Scholar
  169. Roberts, A., et al. (2013). Integrated microscopy techniques for comprehensive pathology evaluation of an implantable left atrial pressure sensor. Journal of Histotechnology, 36, 17–24. Scholar
  170. Rodriguez, J. N., et al. (2014). In vivo response to an implanted shape memory polyurethane foam in a porcine aneurysm model. Journal of Biomedical Materials Research. Part A, 102, 1231–1242. Scholar
  171. Rousselle, S., & Wicks, J. (2008). Preparation of medical devices for evaluation. Toxicologic Pathology, 36, 81–84.PubMedCrossRefGoogle Scholar
  172. Rousselle, S. D., Wicks, J. R., Tabb, B. C., Tellez, A., & O’Brien, M. (2019). Histology strategies for medical implants and interventional device studies. Toxicologic Pathology, 47, 235–249.Google Scholar
  173. Rouselle, S., & Paulin, J. (2019). Medical Devices Special Issue. Toxicologic Pathology, 47, 201–432.Google Scholar
  174. Ruehl-Fehlert, C., et al. (2003). Revised guides for organ sampling and trimming in rats and mice – Part 1. Experimental and Toxicologic Pathology, 55, 91–106. Scholar
  175. Rutgers, M., van Pelt, M. J. P., Dhert, W. J. A., Creemers, L. B., & Saris, D. B. F. (2010). Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage. Osteoarthritis and Cartilage, 18, 12–23. Scholar
  176. Sanders, J. E., Stiles, C. E., & Hayes, C. (2000). Tissue response to single-polymer fibers of varying diameters: Evaluation of fibrous encapsulation and macrophage density. Journal of Biomedical Materials Research, 52, 231–237.PubMedCrossRefGoogle Scholar
  177. Sanjai, K., Kumarswamy, J., Patil, A., Papaiah, L., Jayaram, S., & Krishnan, L. (2012). Evaluation and comparison of decalcification agents on the human teeth. Journal of Oral and Maxillofacial Pathology : JOMFP, 16, 222–227. Scholar
  178. Santerre, J., Woodhouse, K., Laroche, G., & Labow, R. (2005). Understanding the biodegradation of polyurethanes: From classical implants to tissue engineering materials. Biomaterials, 26, 7457–7470.PubMedCrossRefGoogle Scholar
  179. Sato, J., Doi, T., Kanno, T., Wako, Y., Tsuchitani, M., & Narama, I. (2012a). Histopathology of incidental findings in Cynomolgus monkeys (Macaca Fascicularis) used in toxicity studies. Journal of Toxicologic Pathology, 25, 63–101. Scholar
  180. Sato, J., Doi, T., Wako, Y., Hamamura, M., Kanno, T., Tsuchitani, M., & Narama, I. (2012b). Histopathology of incidental findings in beagles used in toxicity studies. Journal of Toxicologic Pathology, 25, 103–134. Scholar
  181. Schmalzried, T. P., Jasty, M., Rosenberg, A., & Harris, W. H. (1993). Histologic identification of polyethylene wear debris using oil red O stain. Journal of Applied Biomaterials, 4, 119–125.PubMedCrossRefGoogle Scholar
  182. Schoen, F. J., Harasaki, H., Kim, K. M., Anderson, H. C., & Levy, R. J. (1988). Biomaterial-associated calcification: Pathology, mechanisms, and strategies for prevention. Journal of Biomedical Materials Research, 22, 11–36.PubMedGoogle Scholar
  183. Schuh, J. C. L. (2008). Medical device regulations and testing for toxicologic pathologists. Toxicologic Pathology, 36, 63–69. Scholar
  184. Schuh, J. C. L. (2015). Genetically modified animal models. In S. C. Gad (Ed.), Animal models in toxicology (3rd ed., pp. 935–956). Boca Raton: CRC Press.CrossRefGoogle Scholar
  185. Schuh, J. C. L., & Funk, K. A. (2019). Compilation of international standards and regulatory guidance documents for evaluation of biomaterials, medical devices, 3D printed and regenerative medicine products. Toxicologic Pathology, 47, 344.PubMedCrossRefGoogle Scholar
  186. Schwartz, R. S., et al. (2004). Preclinical evaluation of drug-eluting stents for peripheral applications: Recommendations from an expert consensus group. Circulation, 110, 2498–2505.PubMedCrossRefGoogle Scholar
  187. Sellers, R. S., et al. (2007). Society of Toxicologic Pathology position paper: Organ weight recommendations for toxicology studies. Toxicologic Pathology, 35, 751–755.PubMedCrossRefGoogle Scholar
  188. Shackelford, C., Long, G., Wolf, J., Okerberg, C., & Herbert, R. (2002). Qualitative and quantitative analysis of nonneoplastic lesions in toxicology studies. Toxicologic Pathology, 30, 93–96. Scholar
  189. Shayesteh Moghaddam, N., et al. (2016). Metals for bone implants: Safety, design, and efficacy. Biomanufacturing Reviews, 1, 1. Scholar
  190. Shea, K. G., Bloebaum, R. D., Avent, J. M., Birk, G. T., & Samuelson, K. M. (1996). Analysis of lymph nodes for polyethylene particles in patients who have had a primary joint replacement. Journal of Bone and Joint Surgery, 78, 497–504.PubMedCrossRefGoogle Scholar
  191. Sheth, S., Litvack, F., Dev, V., Fishbein, M. C., Forrester, J. S., & Eigler, N. (1996). Subacute thrombosis and vascular injury resulting from slotted-tube nitinol and stainless steel stents in a rabbit carotid artery model. Circulation, 94, 1733–1740. Scholar
  192. Shoieb, A., Allavena, R., Swallow, J., & Debrue, M. (2012). Peritoneal sarcomatosis associated with telemetry implants in Sprague Dawley CD rats. Toxicologic Pathology, 40, 113–121.PubMedCrossRefGoogle Scholar
  193. Short, B. G. (2008). Safety evaluation of ocular drug delivery formulations: Techniques and practical considerations. Toxicologic Pathology, 36, 49–62. Scholar
  194. Siddiqui, R. F., Abraham, J. R., & Butany, J. (2009). Bioprosthetic heart valves: Modes of failure. Histopathology, 55, 135–144. Scholar
  195. Signorello, L. B., et al. (2001). Nationwide study of cancer risk among hip replacement patients in Sweden. Journal of the National Cancer Institute, 93, 1405–1410.PubMedCrossRefGoogle Scholar
  196. Socarrás TO, Vasconcelos, A. C., Campos, P. P., Pereira, N. B., Souza, J. P. C., & Andrade, S. P. (2014). Foreign body response to subcutaneous implants in diabetic rats. PLoS One, 9, e110945. Scholar
  197. Soto‐Miranda, M. A., Suami, H., & Chang, D. W. (2013). Mapping superficial lymphatic territories in the rabbit. The Anatomical Record, 296, 965–970.Google Scholar
  198. Stiers, P. J., van Gastel, N., Moermans, K., Stockmans, I., & Carmeliet, G. (2018). An ectopic imaging window for Intravital imaging of engineered bone tissue. JBMR Plus, 2, 92–102.PubMedPubMedCentralCrossRefGoogle Scholar
  199. Stokes, K. (2009). The biocompatibility and biostability of new cardiovascular materials and devices. In Implantable neural prostheses 2 (pp. 1–26). New York: Springer.Google Scholar
  200. Suami, H., Yamashita, S., Soto-Miranda, M. A., & Chang, D. W. (2013). Lymphatic territories (lymphosomes) in a canine: an animal model for investigation of postoperative lymphatic alterations. PLOS ONE, 8:e69222.Google Scholar
  201. Suami, H., & Scaglioni, M. F. (2017). Lymphatic territories (lymphosomes) in the rat: an anatomical study for future lymphatic research. Plastic and reconstructive surgery, 140, 945–951.Google Scholar
  202. Sun, H., Mei, L., Song, C., Cui, X., & Wang, P. (2006). The in vivo degradation, absorption and excretion of PCL-based implant. Biomaterials, 27, 1735–1740. Scholar
  203. Sunderman, F. W., Jr. (1989). Carcinogenicity of metal alloys in orthopedic prostheses: Clinical and experimental studies. Toxicological Sciences, 13, 205–216.CrossRefGoogle Scholar
  204. Szebeni, J. (2012). Hemocompatibility testing for nanomedicines and biologicals: Predictive assays for complement mediated infusion reactions. European Journal of Nanomedicine, 4, 33–53.CrossRefGoogle Scholar
  205. Szeto, G. L., & Lavik, E. B. (2016). Materials design at the interface of nanoparticles and innate immunity. Journal of materials chemistry B, Materials for Biology and Medicine, 4, 1610–1618. Scholar
  206. Tellez, A., Dillon, K. N., & Rousselle, S. D. (2017). Comprehensive preclinical postmortem evaluation of valvular prosthesis. Toxicologic Pathology, 45, 1077–1090. Scholar
  207. Tempel-Brami, C., Schiffenbauer, Y. S., Nyska, A., Ezov, N., Spector, I., Abramovitch, R., & Maronpot, R. R. (2015). Practical applications of in vivo and ex vivo MRI in toxicologic pathology using a novel high-performance compact MRI system. Toxicologic Pathology, 43, 633–650.PubMedCrossRefGoogle Scholar
  208. Teo, Z. W. W., & Schalock, P. C. (2016). Hypersensitivity reactions to implanted metal devices: Facts and fictions. Journal of Investigational Allergology & Clinical Immunology, 26, 279–294. Scholar
  209. Thackaberry, E. A., et al. (2017). Evaluation of the toxicity of Intravitreally injected PLGA microspheres and rods in monkeys and rabbits: Effects of depot size on inflammatory response. Investigative Ophthalmology & Visual Science, 58, 4274–4285.CrossRefGoogle Scholar
  210. The Organisation for Economic Co-operation and Development (2015) General questions and answers concerning OECD principles of Good Laboratory Practice (GLP) and Mutual Acceptance of Data (MAD). European Commission. Accessed 30 May 2017.
  211. Thevenot, P., Hu, W., & Tang, L. (2008). Surface chemistry influence implant biocompatibility. Current Topics in Medicinal Chemistry, 8, 270–280.PubMedPubMedCentralCrossRefGoogle Scholar
  212. Tomlinson, L., et al. (2013). Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries. Veterinary Clinical Pathology, 42, 252–269. Scholar
  213. Tuan, R. S., Lee, F. Y.-I., Konttinen, Y., Wilkinson, J. M., & Smith, R. L. (2008). What are the local and systemic biological reactions and mediators to wear debris and what host factors determine or modulate the biological response to wear particles? The Journal of the American Academy of Orthopaedic Surgeons, 16, S42–S48.PubMedPubMedCentralCrossRefGoogle Scholar
  214. Tuomari, D. L., et al. (2007). Society of toxicologic pathology position paper on pathology image data: Compliance with 21 CFR Parts 58 and 11. Toxicologic Pathology, 35, 450–455.PubMedCrossRefGoogle Scholar
  215. U.S. Food & Drug Administration. (2015). General considerations for animal studies for medical devices. Accessed 25 Aug 2018 2017.
  216. U.S. Food & Drug Administration. (2016). Use of International Standard ISO 10993-1, “Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process” U.S. Department of Health & Human Services. Accessed 23 Oct 2016.
  217. Van Der Giessen, W. J., et al. (1996). Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. Circulation, 94, 1690–1697.PubMedCrossRefGoogle Scholar
  218. Varela, A., & Jolette, J. (2018). Bone toolbox: Biomarkers, imaging tools, biomechanics, and histomorphometry. Toxicologic Pathology, 46, 511–529. Scholar
  219. Veerachamy, S., Yarlagadda, T., Manivasagam, G., & Yarlagadda, P. K. (2014). Bacterial adherence and biofilm formation on medical implants: A review. Proceedings of the Institution of Mechanical Engineers. Part H, 228, 1083–1099.CrossRefGoogle Scholar
  220. Vegas, A. J., et al. (2016). Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nature Biotechnology, 34, 345–352. Scholar
  221. Veiseh, O., et al. (2015). Size- and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nature Materials, 14, 643–651. Scholar
  222. Veleirinho, B., et al. (2014). Foreign body reaction associated with PET and PET/chitosan electrospun nanofibrous abdominal meshes. PLoS One, 9, e95293.PubMedPubMedCentralCrossRefGoogle Scholar
  223. Visuri, T., Pukkala, E., Paavolainen, P., Pulkkinen, P., & Riska, E. B. (1996). Cancer risk after metal on metal and polyethylene on metal total hip arthroplasty. Clinical Orthopaedics and Related Research, 329, S280–S289.CrossRefGoogle Scholar
  224. Von Eiff, C., Jansen, B., Kohnen, W., & Becker, K. (2005). Infections associated with medical devices. Drugs, 65, 179–214.CrossRefGoogle Scholar
  225. Wagenfuhr-Junior, J., Ribas Filho, J. M., Nascimento, M. M., Ribas, F. M., Wanka, M. V., & Godoi Ade, L. (2012). Histopathological reaction over prosthesis surface covered with silicone and polyurethane foam implanted in rats. Acta Cirúrgica Brasileira, 27, 866–873.PubMedCrossRefGoogle Scholar
  226. Walch, A., Rauser, S., Deininger, S.-O., & Höfler, H. (2008). MALDI imaging mass spectrometry for direct tissue analysis: A new frontier for molecular histology. Histochemistry and Cell Biology, 130, 421–434. Scholar
  227. Wancket, L. M. (2019). Regional draining lymph nodes: considerations for medical device studies. Toxicologic Pathology, 47, 339–343.PubMedCrossRefGoogle Scholar
  228. Ward, J. M., & Thoolen, B. (2011). Grading of lesions. Toxicologic Pathology, 39, 745–746. Scholar
  229. Wawrzynski, J., Gil, J. A., Goodman, A. D., & Waryasz, G. R. (2017). Hypersensitivity to orthopedic implants: A review of the literature. Rheumatology and Therapy, 4, 45–56.PubMedPubMedCentralCrossRefGoogle Scholar
  230. Welsing, R. T., van Tienen, T. G., Ramrattan, N., Heijkants, R., Schouten, A. J., Veth, R. P., & Buma, P. (2008). Effect on tissue differentiation and articular cartilage degradation of a polymer meniscus implant a 2-year follow-up study in dogs. American Journal of Sports Medicine, 36, 1978–1989.PubMedCrossRefGoogle Scholar
  231. Weyhe, D., Cobb, W., Lecuivre, J., Alves, A., Ladet, S., Lomanto, D., & Bayon, Y. (2015). Large pore size and controlled mesh elongation are relevant predictors for mesh integration quality and low shrinkage–systematic analysis of key parameters of meshes in a novel minipig hernia model. International Journal of Surgery, 22, 46–53.PubMedCrossRefGoogle Scholar
  232. Williams, D. F. (2008). On the mechanisms of biocompatibility. Biomaterials, 29, 2941–2953.PubMedCrossRefGoogle Scholar
  233. Williams, D. F. (2014). There is no such thing as a biocompatible material. Biomaterials, 35, 10009–10014.PubMedCrossRefGoogle Scholar
  234. Wilson, G. J., et al. (2009). Comparison of inflammatory response after implantation of sirolimus- and paclitaxel-eluting stents in porcine coronary arteries. Circulation, 120, 141–149. Scholar
  235. Witzleb, W.-C., Ziegler, J., Krummenauer, F., Neumeister, V., & Guenther, K.-P. (2006). Exposure to chromium, cobalt and molybdenum from metal-on-metal total hip replacement and hip resurfacing arthroplasty. Acta Orthopaedica, 77, 697–705.PubMedCrossRefGoogle Scholar
  236. Wolf, M. F., & Andwraon, J. M. (2012). Practical approach to blood compatibility assessments: General considerations and standards. In J.-P. Boutrand (Ed.), Biocompatibility and performance of medical devices (pp. 159–206). Philadelphia: Woodhead Publishing. Scholar
  237. Wolf, M. T., Vodovotz, Y., Tottey, S., Brown, B. N., & Badylak, S. F. (2014). Predicting in vivo responses to biomaterials via combined in vitro and in silico analysis. Tissue Engineering. Part C, Methods, 21, 148–159.PubMedPubMedCentralCrossRefGoogle Scholar
  238. Wood, N. K., Kaminski, E. J., & Oglesby, R. J. (1970). The significance of implant shape in experimental testing of biological materials: Disc vs. rod. Journal of Biomedical Materials Research, 4, 1–12.PubMedCrossRefGoogle Scholar
  239. Woodward, S. C., Brewer, P., Moatamed, F., Schindler, A., & Pitt, C. (1985). The intracellular degradation of poly (ε-caprolactone). Journal of Biomedical Materials Research, 19, 437–444.PubMedCrossRefGoogle Scholar
  240. Xie, D., Leng, Y. X., Jing, F. J., & Huang, N. (2015). A brief review of bio-tribology in cardiovascular devices. Biosurface and Biotribology, 1, 249–262. Scholar
  241. Yang, Z., Yuan, H., Tong, W., Zou, P., Chen, W., & Zhang, X. (1996). Osteogenesis in extraskeletally implanted porous calcium phosphate ceramics: Variability among different kinds of animals. Biomaterials, 17, 2131–2137.PubMedCrossRefGoogle Scholar
  242. Zhang, F., Niu, G., Lu, G., & Chen, X. (2011). Preclinical lymphatic imaging. Molecular Imaging and Biology, 13, 599–612.PubMedPubMedCentralCrossRefGoogle Scholar
  243. Zhao, S., Pinholt, E. M., Madsen, J. E., & Donath, K. (2000). Histological evaluation of different biodegradable and non-biodegradable membranes implanted subcutaneously in rats. Journal of Cranio-Maxillo-Facial Surgery, 28, 116–122.PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.JCL Schuh, PLLCBainbridge IslandUSA

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