Tooth regeneration: Current status
Dadu SS. Tooth regeneration: Current status. Indian J Dent Res [serial online] 2009 [cited 2010 Jan 30];20:506-7. Available from: http://www.ijdr.in/text.asp?2009/20/4/506/59444
Tooth loss, commonly seen due to a variety of oral diseases and physiological causes, leads to physical and mental suffering that markedly lower an individual's quality of life. Presence of teeth also helps to prevent dementia as mastication stimulates the brain. [1]
Dentistry has taken the same approach to tooth decay-filling cavities-for decades, but new techniques for rebuilding teeth from inside out could transform the profession over the next decade. [2] Although dental implant therapies have achieved long-term success in the clinic for the recovery of tooth function, dental implants require preexisting high quality bone structures for supporting the implants. Reconstruction of teeth in patients without adequate bone support would be a major advance. [3] Regeneration of a functional and living tooth is one of the most promising therapeutic strategies for the replacement of a diseased or damaged tooth.
Gradually, there seems to be greater convergence between clinical dentistry and bioengineering with which it is possible to regenerate tooth in humans in the near future.
Now the question arises whether the techniques presently available are sufficient to design and fabricate tooth for replacement in clinical dentistry? The present article reviews current research into tooth regeneration.
Currently, there are two major approaches to tooth regeneration: [1]
Tissue regeneration using tissue engineering
Tissue engineering, according to National Institute of Health definition, is an emerging multidisciplinary field involving biology, medicine, and engineering that is likely to revolutionize the way we improve the health and quality of life for millions of people worldwide by restoring, maintaining, or enhancing tissue and organ function, [2] Tissue engineering requires a combination of cells, biodegradable materials, and signaling molecules. This technique has already been applied to the regeneration of the periodontium.
Yelick's group have used dental epithelial and pulpal mesenchymal tissues and seeded the mixture of heterogeneous single cells onto a tooth-shaped biodegradable polymer scaffold, mainly consisting of polyglycolic acid and polycoglycolide copolymer [4] The cell-scaffold constructs were implanted into the body of animal host to receive sufficient blood supply, nutrients, and oxygen. By 25-30 weeks after implantation, tiny tooth-like tissues (such as enamel, dentin, and pulp) were observed within the implants, which resembled the crowns of natural teeth. [4] Although most dental tissues are regenerated using a combination of scaffold materials and dissociated single cells, the success rate for achieving the correct arrangement of a natural tooth is only 15-20%. Further studies are, therefore, required to consistently achieve reconstituted and structurally sound teeth.
Tooth regeneration by reproducing developmental process of tooth formation
This requires an understanding of the basic principles that regulate early tooth development. The natural processes involved in embryonic tooth development were replicated by Sharpe's group. [5] They have placed nondental mesenchymal cells, rather than dental mesenchymal cells (adult bone marrow stromal cell), in contact with embryonic oral epithelium and cultured it for 12 days. The explants containing adult bone marrow stromal cells formed a tooth crown structure comprising enamel; dentin and pulp in few cases, while explants derived from embryonic stem cells or neural stem cells did not form teeth, and only expressed odontogenesis-related genes. These results suggest that stem cells derived from adult bone marrow can take the place of dental mesenchyme for future clinical use, however, no suitable source of epithelial components has yet been found to replace the embryonic oral epithelium.
Hu B et al. have shown that, under experimental conditions, bone marrow cells can give rise to ameloblast-like cells that form enamel [5] , while Sharpe's group reported that bone marrow cells possess the potential to differentiate into dental mesenchymal cells forming dentin and pulp. [6]
These approaches to tooth reconstitution using developing tissues are far from ready for patient application because it would be impractical to use human embryonic tissue. Strategic improvements are also needed prior to clinical application to prevent immune rejection and to overcome ethical issues. [1]
Root generation
Current understanding of the cellular and molecular mechanisms of tooth root development is still in its infancy, although a number of genes involved in tooth crown development have been identified. From a clinical perspective, the most important part of the tooth is the root that supports the crown. Recent technological advances have made possible regeneration of murine tooth, encouraging efforts to regenerate whole human teeth. [3] However, human tooth root development that involves dentin formation, cementum generation, instruction of epithelium, and tooth eruption is a far more complex process which may not be possible with presently available biotechnologies. [3]
Stem cell-mediated root regeneration offers opportunities to regenerate a bioroot and its associated periodontal tissues, which are necessary for maintaining the physiological function of teeth. Sonoyama et al. have explored the potential for reconstructing a functional tooth in miniature pigs in which a bio-root periodontal complex is built up by postnatal stem cells including stem cells from root apical papilla and periodontal ligament stem cells to which an artificial porcelain crown is affixed. This hybrid strategy of autologous dental stem cell engineering may be applicable to human tooth root regeneration. [3]
Even though biotechnology has lead us to regenerate the various components of the tooth, there are certain limitations, which are listed below as suggested by Nakahara and Ide. [1]
Using the principles of bioengineering, tooth regeneration is going to become a realistic possibility within the next few decades.
Regeneration of a functional tooth has the potential to be a promising therapeutic strategy. Experiments have shown that with the use of principles of bioengineering along with adult stem cells, scaffold material, and signaling molecules, tooth regeneration is possible. Research work is in progress on creating a viable bioroot with all its support. A new culture needs to be created that can possibly provide all the nutrients to the stem cells. With the ongoing research, tissue engineering is likely to revolutionize dental health and well-being of people by regenerating teeth over the next decade.
Dentistry has taken the same approach to tooth decay-filling cavities-for decades, but new techniques for rebuilding teeth from inside out could transform the profession over the next decade. [2] Although dental implant therapies have achieved long-term success in the clinic for the recovery of tooth function, dental implants require preexisting high quality bone structures for supporting the implants. Reconstruction of teeth in patients without adequate bone support would be a major advance. [3] Regeneration of a functional and living tooth is one of the most promising therapeutic strategies for the replacement of a diseased or damaged tooth.
Gradually, there seems to be greater convergence between clinical dentistry and bioengineering with which it is possible to regenerate tooth in humans in the near future.
Now the question arises whether the techniques presently available are sufficient to design and fabricate tooth for replacement in clinical dentistry? The present article reviews current research into tooth regeneration.
 Techniques of Tooth Regeneration |  |
Currently, there are two major approaches to tooth regeneration: [1]
- The first is based on tissue engineering involving regeneration of tooth by implanting cells on scaffolding biomaterials.
- The second approach involves reproducing the developmental processes of embryonic tooth formation.
Tissue regeneration using tissue engineering
Tissue engineering, according to National Institute of Health definition, is an emerging multidisciplinary field involving biology, medicine, and engineering that is likely to revolutionize the way we improve the health and quality of life for millions of people worldwide by restoring, maintaining, or enhancing tissue and organ function, [2] Tissue engineering requires a combination of cells, biodegradable materials, and signaling molecules. This technique has already been applied to the regeneration of the periodontium.
Yelick's group have used dental epithelial and pulpal mesenchymal tissues and seeded the mixture of heterogeneous single cells onto a tooth-shaped biodegradable polymer scaffold, mainly consisting of polyglycolic acid and polycoglycolide copolymer [4] The cell-scaffold constructs were implanted into the body of animal host to receive sufficient blood supply, nutrients, and oxygen. By 25-30 weeks after implantation, tiny tooth-like tissues (such as enamel, dentin, and pulp) were observed within the implants, which resembled the crowns of natural teeth. [4] Although most dental tissues are regenerated using a combination of scaffold materials and dissociated single cells, the success rate for achieving the correct arrangement of a natural tooth is only 15-20%. Further studies are, therefore, required to consistently achieve reconstituted and structurally sound teeth.
Tooth regeneration by reproducing developmental process of tooth formation
This requires an understanding of the basic principles that regulate early tooth development. The natural processes involved in embryonic tooth development were replicated by Sharpe's group. [5] They have placed nondental mesenchymal cells, rather than dental mesenchymal cells (adult bone marrow stromal cell), in contact with embryonic oral epithelium and cultured it for 12 days. The explants containing adult bone marrow stromal cells formed a tooth crown structure comprising enamel; dentin and pulp in few cases, while explants derived from embryonic stem cells or neural stem cells did not form teeth, and only expressed odontogenesis-related genes. These results suggest that stem cells derived from adult bone marrow can take the place of dental mesenchyme for future clinical use, however, no suitable source of epithelial components has yet been found to replace the embryonic oral epithelium.
Hu B et al. have shown that, under experimental conditions, bone marrow cells can give rise to ameloblast-like cells that form enamel [5] , while Sharpe's group reported that bone marrow cells possess the potential to differentiate into dental mesenchymal cells forming dentin and pulp. [6]
These approaches to tooth reconstitution using developing tissues are far from ready for patient application because it would be impractical to use human embryonic tissue. Strategic improvements are also needed prior to clinical application to prevent immune rejection and to overcome ethical issues. [1]
Root generation
Current understanding of the cellular and molecular mechanisms of tooth root development is still in its infancy, although a number of genes involved in tooth crown development have been identified. From a clinical perspective, the most important part of the tooth is the root that supports the crown. Recent technological advances have made possible regeneration of murine tooth, encouraging efforts to regenerate whole human teeth. [3] However, human tooth root development that involves dentin formation, cementum generation, instruction of epithelium, and tooth eruption is a far more complex process which may not be possible with presently available biotechnologies. [3]
Stem cell-mediated root regeneration offers opportunities to regenerate a bioroot and its associated periodontal tissues, which are necessary for maintaining the physiological function of teeth. Sonoyama et al. have explored the potential for reconstructing a functional tooth in miniature pigs in which a bio-root periodontal complex is built up by postnatal stem cells including stem cells from root apical papilla and periodontal ligament stem cells to which an artificial porcelain crown is affixed. This hybrid strategy of autologous dental stem cell engineering may be applicable to human tooth root regeneration. [3]
| Limitations in Tooth Regeneration Research | |
Even though biotechnology has lead us to regenerate the various components of the tooth, there are certain limitations, which are listed below as suggested by Nakahara and Ide. [1]
- Whether the principles of tissue engineering related to tooth regeneration can mimic correct tooth morphology?
- Though adult bone marrow cells can replace dental mesenchymal cells, there is no suitable substitute for the embryonic oral epithelium which has a unique set of signals for odontogenesis.
- At present there is no embryonic environment that enables bone marrow cells to differentiate into tooth germ cells.
- There is concern over host immune rejection and ethical issue on use of human embryo.
| Conclusion | |
Using the principles of bioengineering, tooth regeneration is going to become a realistic possibility within the next few decades.
| References | |
| 1. | Nakahara T, Ide Y. Tooth regeneration: implications for the use of bioengineered organs in first wave organ replacement. Hum Cell 2007;20:63-70.  [PUBMED] [FULLTEXT] |
| 2. | Taba M Jr, Jin Q, Sugai JV, Giannobile WV. Current concepts in periodontal bioengineering. Orthod Craniofac Res 2005;8:292-302. [PUBMED] [FULLTEXT] |
| 3. | Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, et al. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS ONE 2006;1:e79. [PUBMED] [FULLTEXT] |
| 4. | 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. [PUBMED] [FULLTEXT] |
| 5. | Hu B, Unda F, Bopp-Kuchler S, Jimenez L, Wang XJ, Haïkel Y, et al. Bone marrow cells can give rise to ameloblast-like cells. J Dent Res 2006; 85: 416-21. |
| 6. | Ohazama A, Modino SA, Miletich I, Sharpe PT. Stem-cell based tissue engineering of murine teeth. J Dent Res 2004;83:518-22. [PUBMED] [FULLTEXT] |
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