Tissue engineering is a multidisciplinary science. The progress of tissue engineering for dental tissues is promising and various dental soft and hard tissues have been regenerated successfully in vitro using stem cells. Prior to their applications practically, there are a number of challenges and unanswered questions that need to be resolved for further progress. It is expected that in next two to three decades, the field of dentistry will be changed significantly by the availability of innovative tissue engineered products in dental office. The objective of this review paper is to highlight the progress of tissue engineering for various dental hard and soft tissues such as enamel, dentin, alveolar bone, periodontium, oral mucosa, and salivary glands. In addition, the challenges in the progress of tissue engineering and future expectations have been discussed.
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Nanci A. Ten Cate’s Oral Histology: Development, Structure, and Function. 8th ed. St. Louis: Mosby; 2012.
Jones FH. Teeth and bones: applications of surface science to dental materials and related biomaterials. Surf Sci Rep 2001;42:75–205.
Zafar MS, Ahmed N. Effects of wear on hardness and stiffness of restorative dental materials. Life Sci J 2014;11:11–18.
Langer R, Vacanti JP. Tissue engineering. Science 1993;260:920–926.
Galler KM, D’Souzab RN, Hartgerink JD. Biomaterials and their potential applications for dental tissue engineering. J Mater Chem 2010;20: 8730–8746.
Nettles DL, Vail TP, Morgan MT, Grinstaff MW, Setton LA. Photocrosslinkable hyaluronan as a scaffold for articular cartilage repair. Ann Biomed Eng 2004;32:391–397.
Ohara T, Itaya T, Usami K, Ando Y, Sakurai H, Honda MJ, et al. Evaluation of scaffold materials for tooth tissue engineering. J Biomed Mater Res A 2010;94:800–805.
Huang GT. Pulp and dentin tissue engineering and regeneration: current progress. Regen Med 2009;4:697–707.
Zafar MS, Al-Samadani KH. Potential use of natural silk for bio-dental applications. J Taibah Univ Med Sci 2014;9:171–177.
Tonomura A, Mizuno D, Hisada A, Kuno N, Ando Y, Sumita Y, et al. Differential effect of scaffold shape on dentin regeneration. Ann Biomed Eng 2010;38:1664–1671.
Goyal B, Tewari S, Duhan J, Sehgal PK. Comparative evaluation of platelet-rich plasma and guided tissue regeneration membrane in the healing of apicomarginal defects: a clinical study. J Endod 2011;37:773–780.
Lim JY, Yi T, Choi JS, Jang YH, Lee S, Kim HJ, et al. Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem cells for amelioration of post-irradiation salivary gland damage. Oral Oncol 2013;49:136–143.
Vacanti CA. The history of tissue engineering. J Cell Mol Med 2006; 10:569–576.
Hermann BW. [On the reaction of the dental pulp to vital amputation and calxyl capping]. Dtsch Zahnarztl Z 1952;7:1446–1447.
Thomas M, Grande D, Haug RH. Development of an in vitro temporomandibular joint cartilage analog. J Oral Maxillofac Surg 1991;49:854–856; discussion 857.
Young CS, Terada S, Vacanti JP, Honda M, Bartlett JD, Yelick PC. Tissue engineering of complex tooth structures on biodegradable polymer scaffolds. J Dent Res 2002;81:695–700.
Duailibi MT, Duailibi SE, Young CS, Bartlett JD, Vacanti JP, Yelick PC. Bioengineered teeth from cultured rat tooth bud cells. J Dent Res 2004; 83:523–528.
Xu WP, Zhang W, Asrican R, Kim HJ, Kaplan DL, Yelick PC. Accurately shaped tooth bud cell-derived mineralized tissue formation on silk scaffolds. Tissue Eng Part A 2008;14:549–557.
Nakao K, Morita R, Saji Y, Ishida K, Tomita Y, Ogawa M, et al. The development of a bioengineered organ germ method. Nat Methods 2007; 4:227–230.
Cawson RA, Odell EW, Porter SR. Cawson’s Essentials of Oral Pathology and Oral Medicine. 7th ed. Edinburgh: Churchill Livingstone; 2002.
Fan Y, Sun Z, Moradian-Oldak J. Controlled remineralization of enamel in the presence of amelogenin and fluoride. Biomaterials 2009;30:478–483.
Moradian-Oldak J. The regeneration of tooth enamel. Dimens Dent Hyg 2009;7:12–15.
Schek RM, Taboas JM, Hollister SJ, Krebsbach PH. Tissue engineering osteochondral implants for temporomandibular joint repair. Orthod Craniofac Res 2005;8:313–319.
OSTBY BN. The role of the blood clot in endodontic therapy. An experimental histologic study. Acta Odontol Scand 1961;19:324–353.
Demarco FF, Conde MC, Cavalcanti BN, Casagrande L, Sakai VT, Nör JE. Dental pulp tissue engineering. Braz Dent J 2011;22:3–13.
Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A 2000;97:13625–13630.
Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, et al. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 2003;100:5807–5812.
Guo W, Gong K, Shi H, Zhu G, He Y, Ding B, et al. Dental follicle cells and treated dentin matrix scaffold for tissue engineering the tooth root. Biomaterials 2012;33:1291–1302.
Li ZY, wang HM, Bao TW. Tissue engineering teeth using bone marrow mesenchymal stem cells with odontogenic potential compounding collagen/ nano-hdroxyapatite composite scaffold. Int J Oral Max Surg 2009; 38:525–526.
Sloan AJ, Smith AJ. Stimulation of the dentine-pulp complex of rat incisor teeth by transforming growth factor-beta isoforms 1-3 in vitro. Arch Oral Biol 1999;44:149–156.
Sloan AJ, Rutherford RB, Smith AJ. Stimulation of the rat dentine-pulp complex by bone morphogenetic protein-7 in vitro. Arch Oral Biol 2000; 45:173–177.
Smith AJ, Tobias RS, Murray PE. Transdentinal stimulation of reactionary dentinogenesis in ferrets by dentine matrix components. J Dent 2001;29:341–346.
Tziafas D. The future role of a molecular approach to pulp-dentinal regeneration. Caries Res 2004;38:314–320.
Saito T, Ogawa M, Hata Y, Bessho K. Acceleration effect of human recombinant bone morphogenetic protein-2 on differentiation of human pulp cells into odontoblasts. J Endod 2004;30:205–208.
Zhang W, Walboomers XF, Wolke JG, Bian Z, Fan MW, Jansen JA. Differentiation ability of rat postnatal dental pulp cells in vitro. Tissue Eng 2005;11:357–368.
Nakashima M, Iohara K, Ishikawa M, Ito M, Tomokiyo A, Tanaka T, et al. Stimulation of reparative dentin formation by ex vivo gene therapy using dental pulp stem cells electrotransfected with growth/differentiation factor 11 (Gdf11). Hum Gene Ther 2004;15:1045–1053.
Almushayt A, Narayanan K, Zaki AE, George A. Dentin matrix protein 1 induces cytodifferentiation of dental pulp stem cells into odontoblasts. Gene Ther 2006;13:611–620.
Huang GT, Shagramanova K, Chan SW. Formation of odontoblast-like cells from cultured human dental pulp cells on dentin in vitro. J Endod 2006;32:1066–1073.
Wei X, Ling J, Wu L, Liu L, Xiao Y. Expression of mineralization markers in dental pulp cells. J Endod 2007;33:703–708.
Wang XY, Zhang Q, Chen Z. A possible role of LIM mineralization protein 1 in tertiary dentinogenesis of dental caries treatment. Med Hypotheses 2007;69:584–586.
Chen S, Gluhak-Heinrich J, Martinez M, Li T, Wu Y, Chuang HH, et al. Bone morphogenetic protein 2 mediates dentin sialophosphoprotein expression and odontoblast differentiation via NF-Y signaling. J Biol Chem 2008;283:19359–19370.
He H, Yu J, Liu Y, Lu S, Liu H, Shi J, et al. Effects of FGF2 and TGFbeta1 on the differentiation of human dental pulp stem cells in vitro. Cell Biol Int 2008;32:827–834.
Cordeiro MM, Dong Z, Kaneko T, Zhang Z, Miyazawa M, Shi S, et al. Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. J Endod 2008;34:962–969.
Arany S, Koyota S, Sugiyama T. Nerve growth factor promotes differentiation of odontoblast-like cells. J Cell Biochem 2009;106:539–545.
Okamoto Y, Sonoyama W, Ono M, Akiyama K, Fujisawa T, Oshima M, et al. Simvastatin induces the odontogenic differentiation of human dental pulp stem cells in vitro and in vivo. J Endod 2009;35:367–372.
Huang GT, Yamaza T, Shea LD, Djouad F, Kuhn NZ, Tuan RS, et al. Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model. Tissue Eng Part A 2010;16:605–615.
Rosa V, Zhang Z, Grande RH, Nör JE. Dental pulp tissue engineering in full-length human root canals. J Dent Res 2013;92:970–975.
Zafar MS, Ahmed N. Nano-Mechanical Evaluation of Dental Hard Tissues Using Indentation Technique. World Appl Sci J 2013;28:1393–1399.
Linde A, Goldberg M. Dentinogenesis. Crit Rev Oral Biol Med 1993; 4:679–728.
Villar CC, Cochran DL. Regeneration of periodontal tissues: guided tissue regeneration. Dent Clin North Am 2010;54:73–92.
Caton JG, Greenstein G. Factors related to periodontal regeneration. Periodontol 2000 1993;1:9–15.
Alsberg E, Hill EE, Mooney DJ. Craniofacial tissue engineering. Crit Rev Oral Biol Med 2001;12:64–75.
Hermann JS, Buser D. Guided bone regeneration for dental implants. Curr Opin Periodontol 1996;3:168–177.
Sood S, Gupta S, Mahendra A. Gene therapy with growth factors for periodontal tissue engineering—a review. Med Oral Patol Oral Cir Bucal 2012;17:e301–e310.
Cho MI, Lin WL, Genco RJ. Platelet-derived growth factor-modulated guided tissue regenerative therapy. J Periodontol 1995;66:522–530.
Howell TH, Fiorellini JP, Paquette DW, Offenbacher S, Giannobile WV, Lynch SE. A phase I/II clinical trial to evaluate a combination of recombinant human platelet-derived growth factor-BB and recombinant human insulin-like growth factor-I in patients with periodontal disease. J Periodontol 1997;68:1186–1193.
Seo S, Na K. Mesenchymal stem cell-based tissue engineering for chondrogenesis. J Biomed Biotechnol 2011;2011:806891.
Vacanti CA, Vacanti JP. Bone and cartilage reconstruction with tissue engineering approaches. Otolaryngol Clin North Am 1994;27:263–276.
van Hout WM, Mink van der Molen AB, Breugem CC, Koole R, Van Cann EM. Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2. Clin Oral Investig 2011;15:297–303.
Warnke PH, Springer IN, Wiltfang J, Acil Y, Eufinger H, Wehmöller M, et al. Growth and transplantation of a custom vascularised bone graft in a man. Lancet 2004;364:766–770.
Warnke PH, Wiltfang J, Springer I, Acil Y, Bolte H, Kosmahl M, et al. Man as living bioreactor: fate of an exogenously prepared customized tissue-engineered mandible. Biomaterials 2006;27:3163–3167.
Chao M, Donovan T, Sotelo C, Carstens MH. In situ osteogenesis of hemimandible with rhBMP-2 in a 9-year-old boy: osteoinduction via stem cell concentration. J Craniofac Surg 2006;17:405–412.
Izumi K, Takacs G, Terashi H, Feinberg SE. Ex vivo development of a composite human oral mucosal equivalent. J Oral Maxillofac Surg 1999;57:571–577; discussion 577-578.
Hotta T, Yokoo S, Terashi H, Komori T. Clinical and histopathological analysis of healing process of intraoral reconstruction with ex vivo produced oral mucosa equivalent. Kobe J Med Sci 2007;53:1–14.
Peramo A, Marcelo CL, Feinberg SE. Tissue engineering of lips and muco-cutaneous junctions: in vitro development of tissue engineered constructs of oral mucosa and skin for lip reconstruction. Tissue Eng Part C Methods 2012;18:273–282.
Sauerbier S, Gutwald R, Wiedmann-Al-Ahmad M, Lauer G, Schmelzeisen R. Clinical application of tissue-engineered transplants. Part I: mucosa. Clin Oral Implants Res 2006;17:625–632.
Aframian DJ, Palmon A. Current status of the development of an artificial salivary gland. Tissue Eng Part B Rev 2008;14:187–198.
de Castro G Jr, Federico MH. Evaluation, prevention and management of radiotherapy-induced xerostomia in head and neck cancer patients. Curr Opin Oncol 2006;18:266–270.
Aframian DJ, Tran SD, Cukierman E, Yamada KM, Baum BJ. Absence of tight junction formation in an allogeneic graft cell line used for developing an engineered artificial salivary gland. Tissue Eng 2002;8:871–878.
Joraku A, Sullivan CA, Yoo JJ, Atala A. Tissue engineering of functional salivary gland tissue. Laryngoscope 2005;115:244–248.
Joraku A, Sullivan CA, Yoo J, Atala A. In-vitro reconstitution of threedimensional human salivary gland tissue structures. Differentiation 2007;75:318–324.
Puelacher WC, Wisser J, Vacanti CA, Ferraro NF, Jaramillo D, Vacanti JP. Temporomandibular joint disc replacement made by tissue-engineered growth of cartilage. J Oral Maxillofac Surg 1994;52:1172–1177; discussion 1177-1178.
Abukawa H, Terai H, Hannouche D, Vacanti JP, Kaban LB, Troulis MJ. Formation of a mandibular condyle in vitro by tissue engineering. J Oral Maxillofac Surg 2003;61:94–100.
Bailey MM, Wang L, Bode CJ, Mitchell KE, Detamore MS. A comparison of human umbilical cord matrix stem cells and temporomandibular joint condylar chondrocytes for tissue engineering temporomandibular joint condylar cartilage. Tissue Eng 2007;13:2003–2010.
Weng Y, Cao Y, Silva CA, Vacanti MP, Vacanti CA. Tissue-engineered composites of bone and cartilage for mandible condylar reconstruction. J Oral Maxillofac Surg 2001;59:185–190.
Khurshid Z, Zafar M, Qasim S, Shahab S, Naseem M, AbuReqaiba A. Advances in nanotechnology for restorative dentistry. Materials 2015;8: 717–731.
Zafar MS, Ahmed N. Nanomechanical characterization of exfoliated and retained deciduous incisors. Technol Health Care 2014;22:785–793.
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Zafar, M.S., Khurshid, Z. & Almas, K. Oral tissue engineering progress and challenges. Tissue Eng Regen Med 12, 387–397 (2015). https://doi.org/10.1007/s13770-015-0030-6
- Dental regeneration
- Tissue engineering challenges
- Guided tissue regeneration