Biocompatibility Issues of Biomaterials

  • Widowati SiswomihardjoEmail author
Part of the Advanced Structured Materials book series (STRUCTMAT, volume 58)


The history of biomaterials started with gold and ivory, when these materials were used by the Egyptians and Romans before the twentieth century. Biomaterial is defined as any non-vital materials used in medical devices, intended to interact with biological systems. An important property that differentiates a biomaterial from other material is its biocompatibility. It is a term that is referred to as the appropriate host response to biomaterials. The understanding of biocompatibility is becoming an interdisciplinary study, since the biocompatibility of biomaterials is a critical issue in limiting device longevity and functionality. Biocompatibility is a multifactorial property, and it can be illustrated as a dynamic and an ongoing process. Some materials, such as amalgam, acrylic resin, and bis-GMA have been used for years in dentistry. On the other hand controversies still arise to debate the biocompatibility of those materials.  Measuring the biocompatibility of a material is very complex. It is based on three levels of tests. Since there is no guarantee that a material is 100 % safe, all regulations and standards are related to the risk and safety of the materials. It is a challenge for biomaterials scientists to provide biomaterials with good biocompatibility that are able to serve for the best result of medical treatments. Gadjah Mada University as a leading university in Indonesia pays a great interest in the field of research. Some studies in developing local biomaterials and medical devices conducted by researchers of Gadjah Mada University are presented in this chapter.


Biomaterials biocompatibility biological response 



My special thanks goes to my colleagues P. Sudiharto, H. Dedy Kusuma, B. Primario Wicaksono, MG. Widiastuti, Punto Dewo, Ika Dewi Ana, H. Agung Pribadi, Purnomo and Y. Novian Paramarthanto who supported me with pictures, references, suggestions and fruitful discussions in completing this chapter.


  1. Ana, I. D., Matsuya, S., & Ishikawa, K. (2010). Engineering of carbonate apatite bone substitute based on composition-transformation of gypsum and calcium hydroxide. J Eng, 4, 344–352.CrossRefGoogle Scholar
  2. Anderson, J. M. (2001). Biological responses to materials. Annual Review of Materials Research, 31, 81–110.CrossRefGoogle Scholar
  3. Anusavice, K. J. (2003). Phillip’s science of dental materials (11th ed.) (pp. 170–190). Elsevier.Google Scholar
  4. Anusavice, K. J., Shen, C., & Rawls, H. R. (2013)1. ). Phillip’s science of dental materials (12th ed.) (pp. 170–190). Elsevier.Google Scholar
  5. Barralet, J., Akao, M., & Aoki, H. (2000). Dissolution of dense carbonate apatite subcutaneously implanted Wistar rats. Journal of Biomedical Materials Research, 49, 176.CrossRefGoogle Scholar
  6. Bergman, C. P., & Stumpf, A. (2013). Dental ceramics, topings in mining. Metallurgy and materials engineering. Heidelberg: Springer.Google Scholar
  7. Bhat, V., Sharma, S. M., Shetty, V., Shastry, C. S., Rao, V., Shenoy, S. M., et al. (2013). Prevalence of Candida-associated denture stomatitis (CADS) and specification of Candida among complete denture wearers of south west coastral region of Karnataka. NUJHS, 3, 59–63.Google Scholar
  8. Bhola, R., Bhola, S. M., Liang, H., & Mishra, B. (2010). Biocompatibility denture polymers—a review. Trends Biomater Artif Organs, 23, 129–136.Google Scholar
  9. Browne, R. M. (1988). The in vitro assessment of the cytotoxicity of dental materials—does it have a role? International Endodontic, 21, 50–58.CrossRefGoogle Scholar
  10. Browne, R. M. (1994). Animal tests for biocompatibility of dental materials relevance, advantages and limitations. Journal of Dentistry, 22, 21–24.CrossRefGoogle Scholar
  11. Chee, W., & Jivraj, S. (2007). Failures in implant dentistry. British Dental Journal, 202, 123–129.CrossRefGoogle Scholar
  12. Chintalwar, S, A., Rajkapoor, B., & Ghode, P. D. (2012). Cytotoxicity of methanolic extract of pisoniaaculeata leaf. International Journal of Pharmacy and Biological Sciences, 3, 155–160.Google Scholar
  13. Craig, R. G., & Powers, J. M. (2002). Restorative dental materials (11th ed.) (pp. 135–140). Mosby.Google Scholar
  14. Dandekeri, S., Sowmya, M. K., & Bhandary, S. (2012). A maxillofacial rehabilitation with velopharyngeal obturator prosthesis. IJBR, 3, 285–287.Google Scholar
  15. Dewo, P., Sharma, P. K., van der Tas, H. F., van der Houwen, E. B., Timmer, M., Magetsari, R., & Busscher, H. J. (2008a). Surface properties of Indonesian-made narrow dynamic compression plates. Medical Journal of Malaysia, 63, 21–23.Google Scholar
  16. Dewo, P., Magetsari, R., Busscher, H. J., van Horn, J. R., & Verkerke, G. J. (2008b). Treating natural disaster victims is dealing with shortages – an orthopaedics perspective. Technical Health Care, 16, 255–259.Google Scholar
  17. Dewo, P., Van Der Houwen, E. B., Sharma, P. K., Magetsari, R., Bor, T. C., Vargas Llona, L. D., Van Horn, J. R., Busscher, H. J., & Verkerke, G. J. (2012). Mechanical properties of Indonesian-made narrow dynamic compression plate. Journal of Mechanical Behavior of Biomedical Materials, 13, 93–101.Google Scholar
  18. Dewo, P., van der Houwen, E. B., Suyitno, Marius, R., Magetsari, R., & Verkerked, G. J. (2015). Redesign of Indonesian-made osteosynthesis plates to enhance their mechanical behavior. Journal of Mechanical Behavior of Biomedical Materials, 42, 274–281.Google Scholar
  19. Duplinsky, T. G., & Cicchetti, D. V. (2012). The health status of dentists exposed to mercury from silver amalgam tooth restorations. International Journal of Statistics in Medical Research, 1, 1–15.Google Scholar
  20. Frinsken, K. W., Dandie, G. W., Lugowski, S., & Jordan, G. (2002). A study of titanium release into body organs following the insertion of single threaded screw implants into the mandibles of sheep. Australian Dental Journal, 47, 214–217.CrossRefGoogle Scholar
  21. Garoushi, S., Lassila, L., & Vallittu, P. K. (2011). Resin-based fiber-reinforced composite for direct replacement of missing anterior teeth- A clinical report. International Journal of Dental, 8455420.Google Scholar
  22. Gautam, R., Singh, R. D., Sharma, V. P., Siddharta, R., Chand, P., & Kumar, R. (2012). Biocompatibility of polymethyl methacrylate resins used in dentistry. Journal of Biomedical Materials Research, 100, 1444–1450.CrossRefGoogle Scholar
  23. Gottenbos, B. (2001). The development of antimicrobial biomaterial surfaces. Thesis. pp. 10–13.Google Scholar
  24. Herliansyah, M. K., Hamdi, M., Ektessabi, A. I., & Wildan, M. W. (2006). Fabrication of hydroxy-apatite bone graft for implant applications—literature study. In Proceeding of First International Conference on manufacturing and material processing (pp. 559–564). Kuala Lumpur, Malaysia.Google Scholar
  25. Illeperuma, R. P., Park, Y. J., Kim, J. M., Bae, J. Y., Che, Z. M., Son, H. K., et al. (2012). Immortalized gingival fibrobalsts as a cytotoxicity test model for dental materials. Journal of Materials Science. Materials in Medicine, 23, 753–762.CrossRefGoogle Scholar
  26. Keong, L. C., & Hlim, A. S. (2009). In vitro models in biocompatibility assessment for biomedical grade chitosan derivatives in wound management. International Journal of Molecular Sciences, 10, 1300–1313.CrossRefGoogle Scholar
  27. Kirkpatrick, C. J., Peters, K., Hermanns, M. I., Bittinger, F., Krump-Konvalinkova, V., Fuchs, S., & Unger, R. E. (2005). In vitro methodologies to evaluate biocompatibility—status quo and perspective. ITBM RBM, 26, 192–199.CrossRefGoogle Scholar
  28. Kostoryz, E. L., Tong, P. Y., Chappelow, C. C., Eick, J. D., Glaros, A. G., & Yourtee, D. M. (1999). In vitro cytotoxicity of solid epoxy-based dental resins and their components. Ent Mat, 15, 363–373.Google Scholar
  29. Landi, E., Tampieri, A., Celotti, G., Langenati, R., Shandri, M., & Sprio, S. (2005). Influence of synthesis and sintering parameters on the characteristics of calcium phosphate. Biomaterials, 26, 2835–2839.CrossRefGoogle Scholar
  30. Lassila, L. V. J., & Vallittu, P. K. (2001). Denture base polymer alldentsinomer—mechanical properties, water sorption and release of residual compounds. Journal of Oral Rehabilitation, 28, 607–613.CrossRefGoogle Scholar
  31. Lawrence, W. H., Dillingham, E. O., Turner, J. E., & Austian, J. (1972). Toxicity profile of chloroacetaldehyde. Journal of Pharmaceutical Sciences, 61, 19–25.CrossRefGoogle Scholar
  32. Leggat, P. A., & Kedjarune, U. (2003). Toxicity of methyl methacrylate in dentistry. International Dental Journal, 53, 126–131.CrossRefGoogle Scholar
  33. Lugoswki, S., Smith, D. C., & Bonek, H. (2000). Systemic metal ion levels in dental implant patientsafter five years. ActualitesenBiomateriaux, Paris France. Romillat, 401–409.Google Scholar
  34. Lundin, K., Schmidt, G., & Bonde, C. (2013). Amalgam tattoo mimicking mucosal melanoma—a diagnostic dilemma revisited. Case Reports in Density, 787294.Google Scholar
  35. Magetsari, R., Van Der Houwen, E. B., Bakker, M. T. J., Van Dr Mei, H. C., Verkerke, G. J., Rakhorst, G., Hilmy, C. R., Van Horn, J. R., & Busscher, H. J. (2006). Biomechanical and surface physico-chemical analyses of used osteosynthesis plates and screws—potential for reuse in developing countries. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 70, 453–460.Google Scholar
  36. Malineni, S. K., Nuvvula, S., Matinlinna, J. P., Yiu, C. K., & King, N. M. (2013). Biocompatibility of various dental materials in contemporary dentistry—a narrative insight. The Journal of Clinical Dentistry, 4, 9–19.Google Scholar
  37. Mehta, R. (2015). Powder metallurgy processing for low-cost titanium. In Materials world magazine.
  38. Moharamzadeh, K., van Noort, R., Brook, I. M., & Scutt, A. M. (2007). Cytotoxicity of resin monomers on human gingival fibroblast and HaCaT keratinocytes. Dental Materials, 23, 40–44.CrossRefGoogle Scholar
  39. Murray, P. E., Godoy, C. G., & Godoy, F. G. (2007). How is the biocompatibility of dental materials evaluated? Medicina Oral, Patología Oral y Cirugía Bucal, 12, 258–256.Google Scholar
  40. Mutter, J. (2011). Is dental amalgam safe for humans? The opinion of the scientific committee of the European commission. Journal of Occupational Medicine, 6, 8–17.CrossRefGoogle Scholar
  41. Nalcaci, A., Oxcan, M. D., & Yilmaz, S. (2006). Citotoxicity of composite resins polymerized with different curing methods. International Endodontic Journal, 37, 151–156.CrossRefGoogle Scholar
  42. Nayak, Y., Rana, R. P., & Pratihar, S. K. (2008). Pressureless sintering of dense hydro-xyapatite- zirconia composites. Journal of Material Science, 19, 2437–2444.Google Scholar
  43. Noor, A. F. M., Kasim, S. R., Othman, R., Ana, I. D., & Ishikawa, K. (2013). Synthesis of biphasic calcium phosphate by hydrothermal route and conversion to porous sintered scaffold. JBNB, 4, 273–278.Google Scholar
  44. Onuki, Y., & Bhardwajd, U. (2008). A review of the biocompatibility of implantable devices—current challenges to overcome foreign body response. Journal of Diabetes Science and Technology, 2, 1003–1010.Google Scholar
  45. Ozcan, M., & Hammerle, C. (2012). Titanium as a reconstruction and implant material in dentistry- Advantages and pitfalls. Materials, 5, 1528–1545.CrossRefGoogle Scholar
  46. Ozen, J., Sipahi, C., Caglar, A., & Dalkiz, M. (2006). In vitro cytotoxicity of glass and carbon fiber-reinforced heat-polymerized acrylic resin denture base material. Turkish Journal of Medical Sciences, 36, 121–126.Google Scholar
  47. Phillips, R. W. (1989). Skinner’s Science of Dental Materials (8th ed.). Philadelphia: WB Saunders Co.Google Scholar
  48. Pleva, J. (1994). Dental mercury– A public health hazard. Reviews on Environmental Health, 10, 1–27.CrossRefGoogle Scholar
  49. Pradeep, N., & Sreekumar, V. (2012). An in vitro investigation into the cytotoxicity of methyl methacrylate monomer. Journal of Contemporary Dental Practice, 6, 838–841.CrossRefGoogle Scholar
  50. Pujiyanto, E., Siswomihardjo, W., Ana, I. D., Tontowi, A. E., & Wildan, M. W. (2006). Cytotoxicity of hydroxyapatite synthesized from local gypsum. In BME days proceeding (pp. 92–95). Bandung.Google Scholar
  51. Pujiyanto, E., Tontowi, A. E., Wildan, M. W., & Siswomihardjo, W. (2013). Preparation of porous hydroxyapatite as synthetic scaffold using powder deposition and sintering and cytotoxicity evaluation. Advanced Materials Research, 747, 123–126.CrossRefGoogle Scholar
  52. Quan, R., Yang, D., Wu, X., Wang, H., Miao, X., & Li, W. (2008). In vitro and in vivo biocompatibility of graded hydroxyapatite – zirconia composite bioceramic. Journal Materials Science, 19, 183–187.Google Scholar
  53. Ratner, B.D., Hoffman, A. S., Schoen, F. J., & Lemons, J. E. (2004). Biomaterials science—an introduction to materials in medicine. Elsevier.Google Scholar
  54. Sakaguchi, R. L., & Powers, J. M. (2012). Craig’s restorative dental materials (13th ed.) (pp. 110–128). Elsevier.Google Scholar
  55. Salerno, C., Pascale, M., Contaldo, M., Esposito, V., Busciolano, M., Milillo, L., Guida, A., Petruzzi, M., & Serpico, R. (2011). Candida associated denture stomatitis. Med Oral Patol Oral Cir Bucal Mar, 16, 139–143.Google Scholar
  56. Schmalz, G., & Arenholt-Bindslev, D. (2009). Biocompatibility of dental materials. Heidelberg: Springer.Google Scholar
  57. Scott, R. M. (1990). Preventing and treating shunt complications. Concepts Neurosurg, 3, 115–121.Google Scholar
  58. Sideridou, I., Achilias, D. S., Spyroudi, C., & Karabela, M. (2004). Water sorption characteristics of light-cured dental resins and composites based on Bis-EMA/PCDMA. Journal of Biomaterials, 25, 367–376.CrossRefGoogle Scholar
  59. Simon, C. G., Antonuci, J. M., Liu, D. W., & Skrtic, D. (2005). In vitro cytotoxicity of amorphous calcium phosphate composites. Journal of Bioactive and Compatible Polymers, 20, 279–295.CrossRefGoogle Scholar
  60. Singh, R., & Dahotre, N. B. (2007). Corrosion degradation prevention by surface modification of biometallic materials. Journal of Materials Science. Materials in Medicine, 18, 725–751.CrossRefGoogle Scholar
  61. Siswomihardjo, W., Sunarintyas, S., & Tontowi, A. E. (2012). The effect of zirconia in hydroxyapatite on Staphylococcus epidermidis growth. International Journal of Biomaterials, 432372.Google Scholar
  62. Soni, R., Bhatnagar, A., Vivek, R., Singh, R., Chaturvedi, T. P., & Singh, A. (2012). A systemic review on mercury toxicity from dental amalgam fillings and its management strategies. Journal of Scientometric Research, 56, 81–92.Google Scholar
  63. Sudiharto, P. (2002). Ventriculoperitoneal shunt using new semilunar valve system for hydrocephalus in infants and children. Indonesia Journal of Clinical Epidemiology and Biostatistics, 9, 56–65.Google Scholar
  64. Sweeney, M., Creanor, S. L., Smith, R. A., & Foye, R. H. (2012). The release of mercury from dental amalgam and potential neurotoxicological effects. Journal of Dentistry, 30, 243–250.CrossRefGoogle Scholar
  65. Tang, A. T. H. (2014). Biocompatibility in Handbook of oral biomaterials (pp. 173–176). Pan Stanford Pub.Google Scholar
  66. Temenoff, J. S., & Mikos, A. G. (2008). Biomaterials—the intersection of biology and materials science (pp. 1–13). Pearson Int Ed.Google Scholar
  67. Triyono, J., Tontowi, A. E., Siswomihardjo, W., & Rochmadi. (2015). Tensile strength test of photo biocomposites for application in biomedical materials. Applied Mechanics and Materials, 699, 411–415.Google Scholar
  68. Tuan Rahmi, T. N. A., Mohamad, D., Akil, H. M., & Abdul Rahman, I. (2012). Water sorption characteristics of restorative dental composites immersed in acidic drinks. Dental Materials, 28, 63–70.Google Scholar
  69. Ucar, Y., & Brantley, W. (2011). Biocompatibility of dental amalgams. International Journal of Dentistry, 981595.Google Scholar
  70. van den Berghe, F., Cornillie, P., Stegen, L., van Goethem, B., & Simoens, P. (2010). Palatoschizis in the dog—development mechanisms and etiology. Vlaams Diergeneeskunde Tijdschrift, 79, 117–123.Google Scholar
  71. van Tienhoven, E. A. E., Korbee, D., Sshipper, L., Verharen, H. W., & de Jong, W.-H. (2006). In vitro and in vivo (cyto)toxicity assays using PVC and LDPE as model materials. Journal of Biomedical Materials Research Part A, 78, 175–182.CrossRefGoogle Scholar
  72. Wang, Q., Ge, S., & Zhang, D. (2004). Highly bioactive nano-hydroxyapatite partially stabilized zirconia ceramics. Journal of Bionic Engineering, 1, 215–220.Google Scholar
  73. Wataha, J. C. (2001). Principles of biocompatibility for dental practioners. Journal of Prosthetic Dentistry, 86, 203–209.CrossRefGoogle Scholar
  74. Wataha, J. C., Hanks, C. T., Strawn, S., & Fat, G. C. (1994). Cytotoxicity of components of resins and other dental restorative materials. Journal of Oral Pathology, 10, 101–112.Google Scholar
  75. Wiliams, D. F. (2008). On the mechanisms of biocompatibility. Biomaterials, 29, 2941–2953.CrossRefGoogle Scholar
  76. Woodman, J. L., Jacobs, J. J., Galante, J. O., & Urban, R. M. (1984). Metal ion release from titanium based prosthetic segmental replacements of long bones in baboons—A long term study. Journal of Orthopaedic Research, 1, 421–430.CrossRefGoogle Scholar
  77. Zhang, M., & Matinlinna, J. P. (2012). E-glass fiber-reinforced composites in dental applications. Silicon, 4, 73–78.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Gadjah Mada UniversityYogyakartaIndonesia

Personalised recommendations