Key Terminology in Biomaterials and Biocompatibility Laleh Ghasemi-Mobarakeh1, Davood Kolahreez1, Seeram Ramakrishna2 and David Williams3

Available online at www.sciencedirect.com Current Opinion in ScienceDirect Biomedical Engineering

Key terminology in biomaterials and biocompatibility Laleh Ghasemi-Mobarakeh1, Davood Kolahreez1, Seeram Ramakrishna2 and David Williams3

Abstract Elsevier [5]. Recently, it has been felt that a fresh look Biomaterials have gained much interest as a very important at these and more recently introduced definitions is category of materials because of their wide application in required, especially because of the developments in medicine and benefit to patient such as increased longevity biomaterials science and the expanded range of their and improved quality of life. The biocompatibility of bio- applications. A conference on the definitions related to materials is an important issue, and many researches have biomaterials was held in Chengdu, China, in 2018 for been devoted during the past decades in this field. In this this purpose, in which 53 outstanding biomaterial ex- review, we will focus on basic concepts and key terminologies perts participated from 17 countries and regions; the in the fields of biomaterials and biocompatibility. Moreover, the proceedings of this conference are also being published most recent definitions of the terms related to biomaterials and by Elsevier [6]. Professor David Williams chaired both biocompatibility provided in the 2018 Chengdu consensus conferences, the former when he was at the University conference are stated. Some standard methods for evaluating of Liverpool and the latter when he was at the Wake the concepts related to biomaterials and biocompatibility are Forest Institute of Regenerative Medicine in the USA. also listed in this article. During the Chengdu conference, the status of consensus and provisional consensus was given to definitions that received over 75% and 50e75% yes votes, Addresses 1 Department of Textile Engineering, Isfahan University of Technology, respectively. This review provides readers with the basic Isfahan 84156-83111, Iran concepts and key terminologies in the fields of bio- 2 Department of Mechanical Engineering, Faculty of Engineering, 2 materials and biocompatibility. Some important terms Engineering Drive 3, National University of Singapore, Singapore are also defined according to the existing literature. In 117576, Singapore 3 addition, the exact definitions of the terms provided in Wake Forest Institute of Regenerative Medicine, Winston-Salem, NC, USA the 2018 consensus conference are stated to draw the attention of readers to the most recent definitions. Corresponding author: Ghasemi-Mobarakeh, Laleh (laleh.ghasemi@ However, some of the terms presented in this review cc.iut.ac.ir) have not been defined in the given conference. Some standard methods for evaluating the concepts related to Current Opinion in Biomedical Engineering 2019, 10:45–50 biomaterials and biocompatibility are given in this article. Figure 1 schematically presents the terms that This review comes from a themed issue on Biomaterials: Biomate- rials and Biocompatibility have been studied in this review. Edited by Masoud Mozafari, Masayuki Yamato and Seeram Ramakrishna Biocompatibility Biocompatibility is defined as the ability of a material to perform its desired functions with respect to a medical therapy, to induce an appropriate host response in a https://doi.org/10.1016/j.cobme.2019.02.004 specific application and to interact with living systems 2468-4511/© 2019 Published by Elsevier Inc. without having any risk of injury, toxicity, or rejection by the immune system and undesirable or inappropriate Keywords local or systemic effects [7e17]. The biocompatibility Biomaterials, Biocompatibility. definition which achieved consensus in the 2018 conference confirmed the definition agreed in 1985 as ‘the Introduction ability of a material to perform with an appropriate host Biomaterials science has significantly contributed to the response in a specific application.’ rapidly growing fields of surgical and medical technolo- gies over several decades [1e3]. The biocompatibility of Biomaterial biomaterials is a very important issue within these fields, The term ‘biomaterial’ had been defined in 1986 as ‘a and many studies have been devoted to the under- nonviable material used in a medical device, intended to standing of biocompatibility phenomena [4]. In March interact with biological systems.’ At that time, bio- 1986, a consensus conference was held in Chester, UK, materials were largely used in medical devices to treat, focusing on‘amplification of the definitions presented in augment, or replace any tissues, organs, or functions of biomaterials,’ the proceeding of which was published by the body without causing any adverse reaction to living www.sciencedirect.com Current Opinion in Biomedical Engineering 2019, 10:45–50 46 Biomaterials: Biomaterials and biocompatibility

Figure 1 Hemocompatibility Hemocompatibility is a feature of biocompatibility describing the compatibility of implanted materials with circulating blood while a medical device can maintain contact with blood without any adverse reactions, such as formation of a thrombus without releasing any components into blood and any undesirable consequences [10,33,34]. The latest definition of this term presented in the 2018 conference is ‘the ability of a blood-contacting biomaterial to (1) avoid the formation of a thrombus by minimal activation of platelets and of blood coagulation, (2) minimize activation of the complement system, and (3) minimize hemolysis.’ However, this definition achieved provisional consensus with 65.9% yes votes. The main difficulty in the discussions was concerned with the differences between the blood compatibility of a biomaterial and medical device because the latter has to take into account the blood flow parameters of the device, whereas the former is an intrinsicpropertyofthematerialalone.

Host response (foreign body reaction) In relation to biomaterials, the host response is considered to be the response of a living system to the presence of a Schematic illustration of terms defined in this article. material, which may or may not be inert and nontoxic and which involves the various components of the immune system. It includes acute and chronic inflammation, may tissues [10,18e20]. The need to redefine biomaterial be associated with granulomatous formation around the arose from the fact that the ‘nonviable’ description was device, and may induce local or systemic immunosup- no longer relevant and also because biomaterials were pression or immunoenhancement. The tissue seen in the being used in many applications other than implanted foreign body reaction usually contains inflammatory cells devices, including drug delivery systems, imaging including monocytes and macrophages (which may fuse to contrast agents, and tissue engineering constructs. The give foreign body giant cells) and cells of the fibrosis that definition of biomaterial that achieved a consensus of often forms a capsule around the implants, especially fi- opinion in the 2018 conference is as follows: ‘A material broblasts and myofibroblasts. A variable level of vascular- designed to take a form that can direct, through in- ization, involving capillaries, is usually seen [10,18,35]. teractions with living systems, the course of any thera- According to the discussion opened up in the 2018 con- peutic or diagnostic procedure.’ It was agreed that this ference, this term was defined as ‘the cellular reaction of term is synonymous with ‘biomedical material.’ the biomaterial/tissue that is initiated by monocyte adhesion to the adsorbed blood protein layer with subse- quent monocyte differentiation to macrophage formation Carcinogenicity that may fuse to form (multinucleated) giant cells, i.e., Carcinogenicity is the ability of a chemical, material, or foreign body giant cells.’ However, no voting was agent to either stimulate tumor occurrence inducing performed for this definition. cancer or increase its incidence when it is implanted, injected, ingested, or inhaled [21e26]. According to the limited discussion opened up in the 2018 conference, Implant this term was defined as ‘the species-dependent po- The term ‘implant’ has been defined as a device inser- tential of a biomaterial to promote the formation of a ted or grafted surgically, either temporarily or perma- tumor, usually a sarcoma, at the site of a biomedical nently, within the body to improve, assist or maintain a device or biomaterial ability or tendency to produce function, or enhance/alter a contour. The implants can cancer.’ However, no voting took place for this term. be made from soft tissues, such as blood vessel grafts, or from synthetic materials, such as hip prosthesis, which Foreign body capsule are mostly inert [25,36e39]. The latest definition As noted previously, the foreign body capsule is defined presented in the 2018 conference that achieved as the dense avascular layer of collagen around the consensus is as follows: ‘A medical device made from one implant which acts as both a structural and biological or more biomaterials that is intentionally placed, either barrier between the tissue and implant [27e32]. totally or partially, within the body.’

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Table 1

The ISO series of guidance documents for biomaterials and biocompatibility.

# ISO number Title

1 ISO 10993-1:2018 Biological evaluation of medical devices—Part 1: Evaluation and testing within a risk management process 2 ISO 10993-2:2006 Biological evaluation of medical devices—Part 2: Animal welfare requirements 3 ISO 10993-3:2014 Biological evaluation of medical devices—Part 3: Tests for genotoxicity, carcinogenicity and reproductive toxicity 4 ISO 10993-4:2017 Biological evaluation of medical devices—Part 4: Selection of tests for interactions with blood 5 ISO 10993-5:2009 Biological evaluation of medical devices—Part 5: Tests for in vitro cytotoxicity 6 ISO 10993-6:2016 Biological evaluation of medical devices—Part 6: Tests for local effects after implantation 7 ISO 10993-7:2008 Biological evaluation of medical devices—Part 7: Ethylene oxide sterilization residuals 8 ISO 10993-9:2009 Biological evaluation of medical devices—Part 9: Framework for identification and quantification of potential degradation products 9 ISO 10993-10:2010 Biological evaluation of medical devices—Part 10: Tests for irritation and skin sensitization 10 ISO 10993-11:2017 Biological evaluation of medical devices—Part 11: Tests for systemic toxicity 11 ISO 10993-12:2012 Biological evaluation of medical devices—Part 12: Sample preparation and reference materials 12 ISO 10993-13:2010 Biological evaluation of medical devices—Part 13: Identification and quantification of degradation products from polymeric medical devices 13 ISO 10993-14:2001 Biological evaluation of medical devices—Part 14: Identification and quantification of degradation products from ceramics 14 ISO 10993-15:2000 Biological evaluation of medical devices—Part 15: Identification and quantification of degradation products from metals and alloys 15 ISO 10993-16:2017 Biological evaluation of medical devices – Part 16: Toxicokinetic study design for degradation products and leachables 16 ISO 10993-17:2002 Biological evaluation of medical devices—Part 17: Establishment of allowable limits for leachable substances 17 ISO 10993-18:2005 Biological evaluation of medical devices—Part 18: Chemical characterization of materials 18 ISO/TS 10993-19:2006 Biological evaluation of medical devices—Part 19: Physico-chemical, morphological and topographical characterization of materials 19 ISO/TS 10993-20:2006 Biological evaluation of medical devices—Part 20: Principles and methods for immunotoxicology testing of medical devices 20 ISO/TR 10993-22:2017 Biological evaluation of medical devices—Part 22: Guidance on nanomaterials 21 ISO/CD 10993-23 Biological evaluation of medical devices—Part 23: Determination of skin irritation of medical device extracts using Reconstructed human Epidermis (RhE) 22 ISO/TR 10993-33:2015 Biological evaluation of medical devices—Part 33: Guidance on tests to evaluate genotoxicity—Supplement to ISO 10993-3 23 ISO/TR 15499:2016 Biological evaluation of medical devices—Guidance on the conduct of biological evaluation within a risk management process 24 ISO/DTS 21726 Biological evaluation of medical devices—Application of the threshold of toxicological concern (TTC) (Under development) for assessing biocompatibility of extractable substances from medical devices 25 ISO 14155:2011 Clinical investigation of medical devices for human subjects—Good clinical practice 26 ISO 22442-1:2015 Medical devices utilizing animal tissues and their derivatives—Part 1: Application of risk management 27 ISO 22442-2:2015 Medical devices utilizing animal tissues and their derivatives—Part 2: Controls on sourcing, collection and handling 28 ISO 22442-3:2007 Medical devices utilizing animal tissues and their derivatives—Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents 29 ISO/TR 22442-4:2010 Medical devices utilizing animal tissues and their derivatives—Part 4: Principles for elimination and/or inactivation of transmissible spongiform encephalopathy (TSE) agents and validation assays for those processes 30 ISO 11737-1:2018 Sterilization of health care products—Microbiological methods—Part 1: Determination of a population of microorganisms on products 31 ISO 11737-2:2009 Sterilization of medical devices—Microbiological methods—Part 2: Tests of sterility performed in the definition, validation and maintenance of a sterilization process 32 ISO 11135:2014 Sterilization of health-care products—Ethylene oxide—Requirements for the development, validation and routine control of a sterilization process for medical devices 33 ISO 7405:2008 Dentistry—Evaluation of biocompatibility of medical devices used in dentistry 34 ISO/TR 37137:2014 Cardiovascular biological evaluation of medical devices—Guidance for absorbable implants 35 ISO 22794:2007 Dentistry—Implantable materials for bone filling and augmentation in oral and maxillofacial surgery—Contents of a technical file 36 ISO 11979-5:2006 Ophthalmic implants—Intraocular lenses—Part 5: Biocompatibility 37 ISO 19227:2018 Implants for surgery—Cleanliness of orthopedic implants—General requirements 38 ISO 5910:2018 Cardiovascular implants and extracorporeal systems—Cardiac valve repair devices 39 ISO 15675:2016 Cardiovascular implants and artificial organs—Cardiopulmonary bypass systems—Arterial blood line filters 40 ISO/TS 22911:2016 Dentistry—Preclinical evaluation of dental implant systems—Animal test methods 41 ISO 14630:2012 Non-active surgical implants—General requirements 42 ISO 17327-1:2018 Non-active surgical implants—Implant coating—Part 1: General requirements 43 ISO 13175-3:2012 Implants for surgery—Calcium phosphates—Part 3: Hydroxyapatite and beta-tricalcium phosphate bone substitutes 44 ISO/TR 37137:2014 Cardiovascular biological evaluation of medical devices—Guidance for absorbable implants 45 ISO 3826-1:2013 Plastics collapsible containers for human blood and blood components—Part 1: Conventional containers 46 ISO 3826-3 Plastics collapsible containers for human blood and blood components—Part 3: Blood bag systems with integrated features

ISO, International Organization for Standardization.

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Medical device [10,40,55e62]. This term was defined as ‘the tendency A medical device was defined in Chester as ‘an instru- of a material in contact with blood to form a thrombus’ ment, apparatus, implement, machine, contrivance, and achieved a consensus of opinion, having more than in vitro reagent, or other similar or related article, 75% yes votes. including any component, part, or accessory, which is intended for use in the diagnosis of disease or other Standard methods for investigation of conditions or in the cure, mitigation, treatment, or biomaterials and biocompatibility prevention of disease, in man.’ This follows the general The suitability of biomaterials used for medical devices definition given by regulatory bodies, and it may not be is usually investigated by a series of standard tests necessary to try to make this more scientific. In [63,64]. The International Organization for Standardi- Chengdu, Williams presented an alternative compre- zation has established the basic regulations of biocom- hensive definition for medical devices as follows: ‘Any patibility evaluation. The goal of this part is to obtain health-care product that is intended for the diagnosis, further updated information on the use of international prevention, or treatment of disease or injury and does standards regarding biomaterials and biocompatibility. not primarily work by effecting a chemical change in the Table 1 summarizes the most important standard body.’ However, this was not formally discussed or methods for the investigation of biomaterials and adopted. biocompatibility, related to the terms given in this article. Mineralization From the point of view of biomaterials, mineralization is Conclusion the precipitation of minerals into a structure such as This review summarizes the definitions provided for biomaterials or prosthetic devices. This normally refers some key terminologies of biomaterials and biocompat- to calcium phosphateebased substances in bones and ibility. Definitions were initially presented according to teeth and is a critical determinant of their strength various published articles, and the latest definitions [25,26,40]. offered in the 2018 consensus conference were then discussed. It should also be noted that with a few terms, Osteoconduction there were few noticeable differences between the Osteoconduction refers to the ability to support the previous definitions and the ones presented in the 2018 growth of bone tissue over the surface or down into conference. However, many had to be significantly pores, channels, or pipes of an implant or graft [41e50]. changed, and the Chengdu conference took the oppor- Osteoconductive materials allow bone-forming cells to tunity to discuss and define terms that had not become infiltrate, proliferate, and then form a new bone in the relevant by 1986, including regenerative medicine, structure of the substrate [48]. According to the limited tissue engineering, organoids, and whole tissue discussion on the term, without voting in the 2018 engineering. conference, the proposed definition was as follows: ‘the process of passively allowing bones to grow and remodel Conflict of interest statement over a surface.’ Nothing declared.

Osteogenesis References Osteogenesis describes the process of bone formation 1. Dee KC, Puleo DA, Bizios R: An introduction to tissue-biomaterial interactions. Wiley; 2003. and development [49,51e54]. Osteogenic materials are 2. Shi D: Biomaterials and tissue engineering. Berlin, Heidelberg: able to form a new bone from osteoblastic cells present Springer Berlin Heidelberg; 2004. in the material [42]. 3. Zivic F, Affatato S, Trajanovic M, Schnabelrauch M, Grujovic N, Choy KL: Biomaterials in clinical practice. Cham: Springer Inter- Osteoinduction national Publishing; 2018. Osteoinduction is the process in which osteogenesis is 4. Williams D: Essential biomaterials science. Cambridge University encouraged. It is also defined as the ability to stimulate Press; 2014. the differentiation of stem cells or osteoprogenitor cells 5. Williams DF: Definitions in biomaterials: proceedings of a consensus conference of the European Society for Biomaterials, to mature bone-forming cells [42,44,50]. Osteoinduc- Chester, Engl., March 3–5, 1986. Elsevier; 1987. tion was defined as ‘action or process of stimulating 6. Zhang X, Williams D, (Eds). Definitions of biomaterials for the osteogenesis’ in the 2018 conference. twenty-first century. Elsevier; 2019. 7. Williams DF: On the mechanisms of biocompatibility. Bio- Thrombogenicity materials 2008, 29:2941–2953. Thrombogenicity is one aspect of hemocompatibility 8. Williams DF: There is no such thing as a biocompatible ma- – and is defined as the ability of a device which stimulates terial. Biomaterials 2014, 35:10009 10014. and/or promotes the formation of a thrombus

Current Opinion in Biomedical Engineering 2019, 10:45–50 www.sciencedirect.com Key terminology in biomaterials and biocompatibility Ghasemi-Mobarakeh et al. 49

9. Williams DF: Biocompatibility pathways: biomaterials-induced 34. Wexler P, Anderson B, de Peyster A, Gad SC, Hakkinen PJB, sterile inflammation, mechanotransduction, and principles of Kamrin M, Locey B, Mehendale HM, Pope C, Shugart L: Ency- biocompatibility control. ACS Biomater Sci Eng 2017, 3:2–35. clopedia of toxicology. 3rd ed. Elsevier Science; 2014. 10. Williams D: The Williams dictionary of biomaterials. Liverpool 35. Lagaron JM, Ocio MJ, Lopez-Rubio A: Antimicrobial polymers. University Press; 1999. Wiley; 2011. 11. Basu B: Biomaterials for musculoskeletal regeneration: concepts. 36. Dictionary AH: The American heritage medical dictionary. Springer Singapore; 2016. Houghton Mifflin Company; 2007. 12. Basu B, Katti DS, Kumar A: Advanced biomaterials: fundamen- 37. Wilkins LW: Stedman’s medical dictionary for the dental pro- tals, processing, and applications. Wiley; 2010. fessions: illustrated. Wolters Kluwer/Lippincott Williams & Wilkins; 2007. 13. dos Santos V, Brandalise RN, Savaris M: Engineering of biomaterials. Springer International Publishing; 2017. 38. Mosby’s medical dictionary – E-book. Elsevier Health Sciences; 2013. 14. Thomas S, Balakrishnan P, Sreekala MS: Fundamental biomaterials: ceramics. Elsevier Science; 2018. 39. Blood DC, Studdert VP, Gay CC: Saunders comprehensive vet- erinary dictionary. 3rd ed. Elsevier Saunders; 2007. 15. Wnek GE, Bowlin GL: Encyclopedia of biomaterials and biomedical engineering. Taylor & Francis; 2008. 40. Ratner BD, Hoffman AS, Schoen FJ, Lemons JE: Biomaterials science: an introduction to materials in medicine. Elsevier Sci- 16. Vladkova TG: Surface engineering of polymeric biomaterials. ence; 2012. Smithers Information Limited; 2013. 41. Anand SC, Kennedy JF, Miraftab M, Rajendran S: Medical textiles 17. Matinlinna JP: Handbook of oral biomaterials. Pan Stanford; and biomaterials for healthcare. Elsevier Science; 2005. 2014. 42. Ducheyne P, Healy KE, Grainger DW, Hutmacher DW, 18. Carter B, Norton G: Ceramic materials. New York: Springer- Kirkpatrick CJ: Comprehensive biomaterials. Elsevier; 2011. Verlag; 2007. 43. Herkowitz HN, Spine ISSL: The Lumbar spine. Lippincott Williams 19. Baust JG, Baust JM: Advances in biopreservation. CRC Press; & Wilkins; 2004. 2006. 44. Gunzburg R, Szpalski M, Passuti N, Aebi M: The use of bone 20. Williams DF: On the nature of biomaterials. Biomaterials 2009, substitutes in spine surgery: a state of the art review. Springer 30:5897–5909. Berlin Heidelberg; 2002. 21. Kuete V: Toxicological Survey of African medicinal plants. 45. Lee JS: Applications of orthodontic mini implants. Quintessence Elsevier; 2014. Publishing Company; 2007. 22. Kitchin KT: Carcinogenicity: testing: predicting, and interpreting 46. Berry DJ, Lieberman J: Surgery of the hip E-book. Elsevier Health chemical effects. Taylor & Francis; 1998. Sciences; 2012. 23. Delogu B: Risk analysis and governance in EU policy making and 47. Herford AS: G. for S.A. in Oral, M. Surgery, B. Brown, Selected regulation: an introductory guide. Springer International Publish- readings in oral and maxillofacial surgery. Guild for Scientific ing; 2016. Advancement in Oral and Maxillofacial Surgery; 2007. 24. Gruiz K, Meggyes T, Fenyvesi E: Engineering tools for environ- 48. Babbush CA, Hahn JA, Krauser JT, Rosenlicht JL: Dental im- mental risk management: 2. Environmental toxicology. CRC plants – E-book: the art and science. Elsevier Health Sciences; Press; 2015. 2010. 25. Miller BF, Keane CB, O’Toole M: Miller-Keane encyclopedia & 49. Korkusuz F: Musculoskeletal research and basic science. dictionary of medicine, nursing & allied health. 7th ed. Saunders; Springer International Publishing; 2015. 2003. 50. Freese A: Principles of molecular neurosurgery. Karger; 2005. 26. Stedman’s, Stedman’s Medical dictionary for the health pro- fessions and nursing. Lippincott Williams & Wilkins; 2008. 51. Lieberman JR, Friedlaender GE: Bone regeneration and repair: biology and clinical applications. Humana Press; 2007. 27. Hetrick EM, Prichard HL, Klitzman B, Schoenfisch MH: Reduced foreign body response at nitric oxide-releasing subcutane- 52. White TD, Folkens PA: The human bone manual. Elsevier Sci- ous implants. Biomaterials 2007, 28:4571–4580. ence; 2005. 28. Bartoli CR, Godleski JJ: Blood flow in the foreign-body cap- 53. Senagore AJ: The gale encyclopedia of surgery. Gale: G-O; 2004. sules surrounding surgically implanted subcutaneous devices. J Surg Res 2010, 158:147–154. 54. Di Silvio L: Cellular response to biomaterials. Elsevier Science; 2008. 29. Irudayaraj JM: Biomedical nanosensors. Pan Stanford; 2012. 55. Vert M, Doi Y, Hellwich K-H, Hess M, Hodge P, Kubisa P, 30. William PHLR, Bruce K: IFATS collection: adipose-derived Rinaudo M, Schué F: Terminology for biorelated polymers and stromal cells improve the foreign body response. Stem Cells applications (IUPAC recommendations 2012). Pure Appl Chem 2008, 26:2691–2695. 2012, 84:377. 31. Nichols SP, Koh A, Brown NL, Rose MB, Sun B, Slomberg DL, 56. Dobrovolskaia Marina A, Mcneil Scott E: Handbook of immuno- Riccio DA, Klitzman B, Schoenfisch MH: The effect of nitric logical properties of engineered nanomaterials. 2nd ed. World oxide surface flux on the foreign body response to subcu- Scientific; 2016 (In 3 Volumes). taneous implants. Biomaterials 2012, 33:6305–6312. 57. Dumitriu S, Popa V: Polymeric biomaterials: medicinal and phar- 32. Bartoli CR, Nadar MM, Godleski JJ: Capsule thickness corre- maceutical applications. CRC Press; 2013. lates with vascular density and blood flow within foreign- body capsules surrounding surgically implanted subcutane- 58. Colman RW: Hemostasis and thrombosis: basic principles and ous devices. Artif Organs 2010, 34:857–861. clinical practice. Lippincott Williams & Wilkins; 2006. 33. Rosen Y, Elman N: Biomaterials science: an integrated clinical 59. Atala A, Lanza R, Nerem R, Thomson JA: Principles of regener- and engineering approach. Taylor & Francis; 2012. ative medicine. Elsevier Science; 2011.

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60. Bodnar E, Frater R: Replacement cardiac valves. McGraw-Hill; microscopy combined with a parallel plate flow cell. Artif 1992. Organs 1994, 18:588–595. 61. Murphy W, Black J, Hastings G: Handbook of biomaterial prop- 63. Ramakrishna S, Tian L, Wang C, Liao S, Teo WE: Medical de- erties. New York: Springer; 2016. vices: regulations, standards and practices. Elsevier; 2015. 62. Nobuchika K, Chisato N, Kazuhisa S, Takayuki K, Hirofumi N, 64. Williams DF: Regulatory biocompatibility requirements for Toshiyuki K, Kiyotaka S, Hitoshi K, Tetsuzo A: In vitro evaluation biomaterials used in regenerative medicine. J Mater Sci Mater of platelet/biomaterial interactions in an epifluorescent video Med 2015, 26:89.

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