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Whole Tooth Engineering

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Applications of Biomedical Engineering in Dentistry

Abstract

There are several challenges in using common removable artificial dental implants, including high risk of bone loss and implant failure. Therefore, bioengineering of physiologically functional whole teeth using regenerative approaches seems essential. To a bioengineer a whole tooth, autologous stem cell-seeded scaffolds, and stem cell reassociations can be implanted at the site of the tooth loss, where they may develop and erupt similarly to a natural tooth. Successful bioengineering of a whole tooth requires appropriate cell source(s), scaffolds, and the induction of the cascade expression of special genes involved in tooth development. To achieve such tooth therapy, we need to fully understand the structure and interaction procedure of epithelial/mesenchymal stem cells during embryonic development of teeth. In this chapter, we first focus on different cell sources and cell signaling pathways through which different parts of a tooth form during tooth development. Then, we describe the recent methods employed for bioengineering a whole tooth, including the organ germ method, sheet engineering, and scaffold-based tissue engineering. Ultimately, the functionality of an engineered whole tooth and future prospects of whole tooth engineering are discussed.

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References

  1. Kassebaum, N., et al. (2017). Global, regional, and national prevalence, incidence, and disability-adjusted life years for oral conditions for 195 countries, 1990–2015: A systematic analysis for the global burden of diseases, injuries, and risk factors. Journal of Dental Research, 96(4), 380–387.

    Article  Google Scholar 

  2. Greenstein, G., Cavallaro, J., Romanos, G., & Tarnow, D. (2008). Clinical recommendations for avoiding and managing surgical complications associated with implant dentistry: A review. Journal of Periodontology, 79(8), 1317–1329.

    Article  Google Scholar 

  3. Jung, R. E., Pjetursson, B. E., Glauser, R., Zembic, A., Zwahlen, M., & Lang, N. P. (2008). A systematic review of the 5-year survival and complication rates of implant-supported single crowns. Clinical Oral Implants Research, 19(2), 119–130.

    Article  Google Scholar 

  4. Lai, W.-F., Lee, J.-M., & Jung, H.-S. (2014). Molecular and engineering approaches to regenerate and repair teeth in mammals. Cellular and Molecular Life Sciences, 71(9), 1691–1701.

    Article  Google Scholar 

  5. Zhang, Y. D., Zhi, C., Song, Y. Q., Chao, L., & Chen, Y. P. (2005). Making a tooth: Growth factors, transcription factors, and stem cells. Cell Research, 15(5), 301.

    Article  Google Scholar 

  6. Ikeda, E., et al. (2009). Fully functional bioengineered tooth replacement as an organ replacement therapy. Proceedings of the National Academy of Sciences, 106(32), 13475–13480.

    Article  Google Scholar 

  7. Oshima, M., et al. (2011). Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy. PLoS One, 6(7), e21531.

    Article  Google Scholar 

  8. Gao, Z., et al. (2016). Bio-root and implant-based restoration as a tooth replacement alternative. Journal of Dental Research, 95(6), 642–649.

    Article  Google Scholar 

  9. Young, C. S., et al. (2005). Tissue-engineered hybrid tooth and bone. Tissue Engineering, 11(9–10), 1599–1610.

    Article  Google Scholar 

  10. Egusa, H., et al. (2010). Gingival fibroblasts as a promising source of induced pluripotent stem cells. PLoS One, 5(9), e12743.

    Article  Google Scholar 

  11. Wada, N., Wang, B., Lin, N. H., Laslett, A. L., Gronthos, S., & Bartold, P. M. (2011). Induced pluripotent stem cell lines derived from human gingival fibroblasts and periodontal ligament fibroblasts. Journal of Periodontal Research, 46(4), 438–447.

    Article  Google Scholar 

  12. Yan, X., Qin, H., Qu, C., Tuan, R. S., Shi, S., & Huang, G. T.-J. (2010). iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin. Stem Cells and Development, 19(4), 469–480.

    Article  Google Scholar 

  13. Amirabad, L. M., et al. (2017). Enhanced cardiac differentiation of human cardiovascular disease patient-specific induced pluripotent stem cells by applying unidirectional electrical pulses using aligned electroactive nanofibrous scaffolds. ACS Applied Materials & Interfaces, 9(8), 6849–6864.

    Article  Google Scholar 

  14. Liu, L., Liu, Y. F., Zhang, J., Duan, Y. Z., & Jin, Y. (2016). Ameloblasts serum-free conditioned medium: Bone morphogenic protein 4-induced odontogenic differentiation of mouse induced pluripotent stem cells. Journal of Tissue Engineering and Regenerative Medicine, 10(6), 466–474.

    Article  Google Scholar 

  15. Ozeki, N., et al. (2013). Mouse-induced pluripotent stem cells differentiate into odontoblast-like cells with induction of altered adhesive and migratory phenotype of integrin. PLoS One, 8(11), e80026.

    Article  Google Scholar 

  16. Zamanlui, S., Amirabad, L. M., Soleimani, M., & Faghihi, S. (2018). Influence of hydrodynamic pressure on chondrogenic differentiation of human bone marrow mesenchymal stem cells cultured in perfusion system. Biologicals, 56, 1–8.

    Article  Google Scholar 

  17. Amari, A., et al. (2015). In vitro generation of IL-35-expressing human Wharton’s jelly-derived mesenchymal stem cells using lentiviral vector. Iranian Journal of Allergy, Asthma, and Immunology, 14(4), 416–426.

    MathSciNet  Google Scholar 

  18. Gronthos, S., Mankani, M., Brahim, J., Robey, P. G., & Shi, S. (2000). Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proceedings of the National Academy of Sciences, 97(25), 13625–13630.

    Article  Google Scholar 

  19. Seo, B.-M., et al. (2004). Investigation of multipotent postnatal stem cells from human periodontal ligament. The Lancet, 364(9429), 149–155.

    Article  Google Scholar 

  20. Miura, M., et al. (2003). SHED: Stem cells from human exfoliated deciduous teeth. Proceedings of the National Academy of Sciences, 100(10), 5807–5812.

    Article  Google Scholar 

  21. Cordeiro, M. M., et al. (2008). Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. Journal of Endodontics, 34(8), 962–969.

    Article  Google Scholar 

  22. Ge, J., et al. (2013). Distal C terminus of CaV1. 2 channels plays a crucial role in the neural differentiation of dental pulp stem cells. PLoS One, 8(11), e81332.

    Article  Google Scholar 

  23. Guo, W., et al. (2009). The use of dentin matrix scaffold and dental follicle cells for dentin regeneration. Biomaterials, 30(35), 6708–6723.

    Article  Google Scholar 

  24. Morsczeck, C., et al. (2005). Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biology, 24(2), 155–165.

    Article  Google Scholar 

  25. Sonoyama, W., et al. (2008). Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: A pilot study. Journal of Endodontics, 34(2), 166–171.

    Article  Google Scholar 

  26. Saito, M. T., Silvério, K. G., Casati, M. Z., Sallum, E. A., & Nociti, F. H., Jr. (2015). Tooth-derived stem cells: Update and perspectives. World Journal of Stem Cells, 7(2), 399.

    Article  Google Scholar 

  27. Okamoto, T., et al. (2002). Clonal heterogeneity in differentiation potential of immortalized human mesenchymal stem cells. Biochemical and Biophysical Research Communications, 295(2), 354–361.

    Article  Google Scholar 

  28. Shinmura, Y., Tsuchiya, S., Hata, K., & Honda, M. J. (2008). Quiescent epithelial cell rests of Malassez can differentiate into ameloblast-like cells. Journal of Cellular Physiology, 217(3), 728–738.

    Article  Google Scholar 

  29. Honda, M., Shinohara, Y., Hata, K., & Ueda, M. (2007). Subcultured odontogenic epithelial cells in combination with dental mesenchymal cells produce enamel–dentin-like complex structures. Cell Transplantation, 16(8), 833–847.

    Article  Google Scholar 

  30. Liu, Y., et al. (2013). Skin epithelial cells as possible substitutes for ameloblasts during tooth regeneration. Journal of Tissue Engineering and Regenerative Medicine, 7(12), 934–943.

    Article  Google Scholar 

  31. Jussila, M., Juuri, E., & Thesleff, I. (2013). Tooth morphogenesis and renewal. In Stem cells in craniofacial development and regeneration (pp. 109–134). Hoboken: Wiley-Blackwell.

    Chapter  Google Scholar 

  32. Wu, P., et al. (2013). Specialized stem cell niche enables repetitive renewal of alligator teeth. Proceedings of the National Academy of Sciences, 110(22), E2009–E2018.

    Article  Google Scholar 

  33. Laurikkala, J., Mikkola, M. L., James, M., Tummers, M., Mills, A. A., & Thesleff, I. (2006). p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation. Development, 133(8), 1553–1563.

    Article  Google Scholar 

  34. Bei, M. (2009). Molecular genetics of tooth development. Current Opinion in Genetics & Development, 19(5), 504–510.

    Article  Google Scholar 

  35. Mikkola, M. L. (2009). Molecular aspects of hypohidrotic ectodermal dysplasia. American Journal of Medical Genetics Part A, 149(9), 2031–2036.

    Article  Google Scholar 

  36. Pispa, J., et al. (1999). Cusp patterning defect in Tabby mouse teeth and its partial rescue by FGF. Developmental Biology, 216(2), 521–534.

    Article  Google Scholar 

  37. Mustonen, T., et al. (2003). Stimulation of ectodermal organ development by Ectodysplasin-A1. Developmental Biology, 259(1), 123–136.

    Article  Google Scholar 

  38. Jernvall, J., Keränen, S. V., & Thesleff, I. (2000). Evolutionary modification of development in mammalian teeth: Quantifying gene expression patterns and topography. Proceedings of the National Academy of Sciences, 97(26), 14444–14448.

    Article  Google Scholar 

  39. Kratochwil, K., Galceran, J., Tontsch, S., Roth, W., & Grosschedl, R. (2002). FGF4, a direct target of LEF1 and Wnt signaling, can rescue the arrest of tooth organogenesis in Lef1−/− mice. Genes & Development, 16(24), 3173–3185.

    Article  Google Scholar 

  40. Klein, O. D., et al. (2006). Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling. Developmental Cell, 11(2), 181–190.

    Article  Google Scholar 

  41. Gritli-Linde, A., Bei, M., Maas, R., Zhang, X. M., Linde, A., & McMahon, A. P. (2002). Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization. Development, 129(23), 5323–5337.

    Article  Google Scholar 

  42. Nakashima, M., & Reddi, A. H. (2003). The application of bone morphogenetic proteins to dental tissue engineering. Nature Biotechnology, 21(9), 1025.

    Article  Google Scholar 

  43. Nakao, K., et al. (2007). The development of a bioengineered organ germ method. Nature Methods, 4(3), 227.

    Article  Google Scholar 

  44. Hu, B., Nadiri, A., Bopp-Kuchler, S., Perrin-Schmitt, F., Wang, S., & Lesot, H. (2005). Dental epithelial histo-morphogenesis in the mouse: Positional information versus cell history. Archives of Oral Biology, 50(2), 131–136.

    Article  Google Scholar 

  45. Hu, B., Nadiri, A., Kuchler-Bopp, S., Perrin-Schmitt, F., Peters, H., & Lesot, H. (2006). Tissue engineering of tooth crown, root, and periodontium. Tissue Engineering, 12(8), 2069–2075.

    Article  Google Scholar 

  46. Ikeda, E., & Tsuji, T. (2008). Growing bioengineered teeth from single cells: Potential for dental regenerative medicine. Expert Opinion on Biological Therapy, 8(6), 735–744.

    Article  Google Scholar 

  47. Lechguer, A. N., et al. (2011). Cell differentiation and matrix organization in engineered teeth. Journal of Dental Research, 90(5), 583–589.

    Article  Google Scholar 

  48. Oshima, M., & Tsuji, T. (2015). Whole tooth regeneration as a future dental treatment. In Engineering Mineralized and Load Bearing Tissues (pp. 255–269). Cham: Springer.

    Chapter  Google Scholar 

  49. Hu, X., et al. (2014). Conserved odontogenic potential in embryonic dental tissues. Journal of Dental Research, 93(5), 490–495.

    Article  Google Scholar 

  50. Ohazama, A., Modino, S., Miletich, I., & Sharpe, P. (2004). Stem-cell-based tissue engineering of murine teeth. Journal of Dental Research, 83(7), 518–522.

    Article  Google Scholar 

  51. Otsu, K., et al. (2011). Differentiation of induced pluripotent stem cells into dental mesenchymal cells. Stem Cells and Development, 21(7), 1156–1164.

    Article  Google Scholar 

  52. Wen, Y., et al. (2012). Application of induced pluripotent stem cells in generation of a tissue-engineered tooth-like structure. Tissue Engineering Part A, 18(15–16), 1677–1685.

    Article  Google Scholar 

  53. Cai, J., et al. (2013). Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells. Cell Regeneration, 2(1), 6.

    Article  Google Scholar 

  54. Wang, B., et al. (2010). Induction of human keratinocytes into enamel-secreting ameloblasts. Developmental Biology, 344(2), 795–799.

    Article  Google Scholar 

  55. Chen, Y., et al. (2015). Human umbilical cord mesenchymal stem cells: A new therapeutic option for tooth regeneration. Stem Cells International, 2015, 1.

    Google Scholar 

  56. Young, C., Terada, S., Vacanti, J., Honda, M., Bartlett, J., & Yelick, P. (2002). Tissue engineering of complex tooth structures on biodegradable polymer scaffolds. Journal of Dental Research, 81(10), 695–700.

    Article  Google Scholar 

  57. Angelova Volponi, A., Kawasaki, M., & Sharpe, P. (2013). Adult human gingival epithelial cells as a source for whole-tooth bioengineering. Journal of Dental Research, 92(4), 329–334.

    Article  Google Scholar 

  58. Kuchler-Bopp, S., et al. (2017). Promoting bioengineered tooth innervation using nanostructured and hybrid scaffolds. Acta Biomaterialia, 50, 493–501.

    Article  Google Scholar 

  59. Chen, G., et al. (2015). Combination of aligned PLGA/Gelatin electrospun sheets, native dental pulp extracellular matrix and treated dentin matrix as substrates for tooth root regeneration. Biomaterials, 52, 56–70.

    Article  Google Scholar 

  60. Rasperini, G., et al. (2015). 3D-printed bioresorbable scaffold for periodontal repair. Journal of Dental Research, 94(9_suppl), 153S–157S.

    Article  Google Scholar 

  61. Zhang, Y., et al. (2006). Novel chitosan/collagen scaffold containing transforming growth factor-β1 DNA for periodontal tissue engineering. Biochemical and Biophysical Research Communications, 344(1), 362–369.

    Article  Google Scholar 

  62. Zhang, W., Vazquez, B., Oreadi, D., & Yelick, P. (2017). Decellularized tooth bud scaffolds for tooth regeneration. Journal of Dental Research, 96(5), 516–523.

    Article  Google Scholar 

  63. Song, J., Takimoto, K., Jeon, M., Vadakekalam, J., Ruparel, N., & Diogenes, A. (2017). Decellularized human dental pulp as a scaffold for regenerative endodontics. Journal of Dental Research, 96(6), 640–646.

    Article  Google Scholar 

  64. Traphagen, S. B., et al. (2012). Characterization of natural, decellularized and reseeded porcine tooth bud matrices. Biomaterials, 33(21), 5287–5296.

    Article  Google Scholar 

  65. Hu, L., et al. (2017). Decellularized swine dental pulp as a bioscaffold for pulp regeneration. BioMed Research International, 2017, 9342714.

    Google Scholar 

  66. Owaki, T., Shimizu, T., Yamato, M., & Okano, T. (2014). Cell sheet engineering for regenerative medicine: Current challenges and strategies. Biotechnology Journal, 9(7), 904–914.

    Article  Google Scholar 

  67. Okano, T. (2014). Current progress of cell sheet tissue engineering and future perspective. Tissue Engineering Part A, 20(9–10), 1353–1354.

    Article  Google Scholar 

  68. Yang, B., et al. (2012). Tooth root regeneration using dental follicle cell sheets in combination with a dentin matrix-based scaffold. Biomaterials, 33(8), 2449–2461.

    Article  Google Scholar 

  69. Zhou, Y., Li, Y., Mao, L., & Peng, H. (2012). Periodontal healing by periodontal ligament cell sheets in a teeth replantation model. Archives of Oral Biology, 57(2), 169–176.

    Article  Google Scholar 

  70. Na, S., et al. (2016). Regeneration of dental pulp/dentine complex with a three-dimensional and scaffold-free stem-cell sheet-derived pellet. Journal of Tissue Engineering and Regenerative Medicine, 10(3), 261–270.

    Article  Google Scholar 

  71. Wei, F., et al. (2013). Functional tooth restoration by allogeneic mesenchymal stem cell-based bio-root regeneration in swine. Stem Cells and Development, 22(12), 1752–1762.

    Article  Google Scholar 

  72. Wise, G., & King, G. (2008). Mechanisms of tooth eruption and orthodontic tooth movement. Journal of Dental Research, 87(5), 414–434.

    Article  Google Scholar 

  73. Wise, G., Frazier-Bowers, S., & D’souza, R. (2002). Cellular, molecular, and genetic determinants of tooth eruption. Critical Reviews in Oral Biology & Medicine, 13(4), 323–335.

    Article  Google Scholar 

  74. Hou, L.-T., et al. (1999). Characterization of dental follicle cells in developing mouse molar. Archives of Oral Biology, 44(9), 759–770.

    Article  Google Scholar 

  75. Gridelli, B., & Remuzzi, G. (2000). Strategies for making more organs available for transplantation. New England Journal of Medicine, 343(6), 404–410.

    Article  Google Scholar 

  76. Bas, O., De-Juan-Pardo, E. M., Catelas, I., & Hutmacher, D. W. (2018). The quest for mechanically and biologically functional soft biomaterials via soft network composites. Advanced Drug Delivery Reviews, 132, 214–234.

    Article  Google Scholar 

  77. Nanci, A. (2017). Ten Cate’s oral histology: Development, structure, and function. Elsevier Health Sciences, St. Louis, Missouri.

    Google Scholar 

  78. Jamal, H. (2016). Tooth organ bioengineering: Cell sources and innovative approaches. Dentistry Journal, 4(2), 18.

    Article  Google Scholar 

  79. Saxena, S. (2015). Tissue response to mechanical load in dental implants. International Journal of Oral & Maxillofacial Pathology, 6(3), 02–06.

    Google Scholar 

  80. Xiu, P., et al. (2016). Tailored surface treatment of 3D printed porous Ti6Al4V by microarc oxidation for enhanced osseointegration via optimized bone in-growth patterns and interlocked bone/implant interface. ACS Applied Materials & Interfaces, 8(28), 17964–17975.

    Article  Google Scholar 

  81. Luukko, K., Kvinnsland, I. H., & Kettunen, P. (2005). Tissue interactions in the regulation of axon pathfinding during tooth morphogenesis. Developmental Dynamics, 234(3), 482–488.

    Article  Google Scholar 

  82. Tuisku, F., & Hildebrand, C. (1994). Evidence for a neural influence on tooth germ generation in a polyphyodont species. Developmental Biology, 165(1), 1–9.

    Article  Google Scholar 

  83. Zhao, H., et al. (2014). Secretion of shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor. Cell Stem Cell, 14(2), 160–173.

    Article  Google Scholar 

  84. Kjaer, M., Beyer, N., & Secher, N. (1999). Exercise and organ transplantation. Scandinavian Journal of Medicine & Science in Sports, 9(1), 1–14.

    Article  Google Scholar 

  85. Burns, D. R., Beck, D. A., & Nelson, S. K. (2003). A review of selected dental literature on contemporary provisional fixed prosthodontic treatment: report of the Committee on Research in Fixed Prosthodontics of the Academy of Fixed Prosthodontics. The Journal of Prosthetic Dentistry, 90(5), 474–497.

    Article  Google Scholar 

  86. Luukko, K., et al. (2008). Secondary induction and the development of tooth nerve supply. Annals of Anatomy-Anatomischer Anzeiger, 190(2), 178–187.

    Article  Google Scholar 

  87. Ibarra, A., et al. (2007). Cyclosporin-A enhances non-functional axonal growing after complete spinal cord transection. Brain Research, 1149, 200–209.

    Article  Google Scholar 

  88. Kökten, T., Bécavin, T., Keller, L., Weickert, J.-L., Kuchler-Bopp, S., & Lesot, H. (2014). Immunomodulation stimulates the innervation of engineered tooth organ. PLoS One, 9(1), e86011.

    Article  Google Scholar 

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Authors and Affiliations

  1. Marquette University School of Dentistry, Milwaukee, WI, USA

    Leila Mohammadi Amirabad, Amanda Lindemuth & Lobat Tayebi

  2. Color and Polymer Research Center (CPRC), Amirkabir University of Technology, Tehran, Iran

    Payam Zarrintaj

  3. Polymer Engineering Department, Faculty of Engineering, Urmia University, Urmia, Iran

    Payam Zarrintaj

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  1. Leila Mohammadi Amirabad
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  2. Payam Zarrintaj
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  4. Lobat Tayebi
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Correspondence to Lobat Tayebi .

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  1. Marquette University School of Dentistry, Milwaukee, WI, USA

    Lobat Tayebi

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Mohammadi Amirabad, L., Zarrintaj, P., Lindemuth, A., Tayebi, L. (2020). Whole Tooth Engineering. In: Tayebi, L. (eds) Applications of Biomedical Engineering in Dentistry. Springer, Cham. https://doi.org/10.1007/978-3-030-21583-5_19

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