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Tooth Tissue Engineering and Regeneration—a Translational Vision!School of Dentistry, University of Birmingham, St Chad’s Queensway, Birmingham B4 6NN, UK; a.j.smith{at}bham.ac.uk Restoration of lost tooth tissue, whether from disease or trauma, represents a significant proportion of the daily routine for many practicing clinicians. The recent WHO World Oral Health Report 2003 identified caries as a continuing global problem, with an estimated five billion people worldwide having experienced the disease. Treatment costs are estimated as accounting for some 5–10% of the healthcare budgets in industrialized countries (WHO, 2004). Thus, the challenge and resource burden of restoring lost tooth tissue will be with us for many years to come. Two reports in the present issue of the Journal of Dental Research highlight exciting advances in moving toward the tissue engineering of teeth. Yelick’s group and collaborators have seeded cultured tooth germ cells on bio-degradable scaffolds which were then implanted to bioengineer tooth tissues (Duailibi et al., 2004), while Sharpe’s group have been able to generate tooth structures from non-dental mesenchymal cells placed in contact with embryonic oral epithelium and transplanted to an ectopic site (Ohazama et al., 2004). The latter report is pivotal in that it demonstrates that uncommitted mesenchymal stem cells, in association with oral epithelium, can be instructed to mimic developmental events leading to growth of a tooth structure comprised of enamel, dentin, and pulp, with a morphology resembling that of a natural tooth. These observations offer very exciting opportunities for replacement of natural teeth damaged through disease or trauma and for those missing in hypodontia. There are obvious practical obstacles still to be overcome before this might be available as a routine clinical treatment, but it provides an elegant example of the translation of basic science research to the clinical arena. The last 10 to 20 years have seen rapid advances in our understanding of the molecular control of cellular behavior during embryonic tooth development, leading to the programming and differentiation of cells responsible for secretion of the dental tissues comprising an intact tooth. Seminal contributions have come from dental scientists in the field of developmental biology throughout the world to provide the foundation of knowledge upon which we can build future strategies for the tissue engineering of teeth. There are also significant opportunities to exploit this knowledge for the development of novel regenerative therapies, which seek to restore partial tooth tissue loss. Such approaches provide potential for restoration of the structural integrity of the dental tissues where the new tissues become an integral part of the tooth, thus minimizing some of the problems of restoration failure with traditional dental materials through interface failure and bacterial microleakage, etc. David Williams, Director of the UK Centre for Tissue Engineering, recently highlighted the tremendous potential for regenerative medicine’s impact on clinical treatment during a plenary lecture at the British Division meeting of the IADR. Of course, dentistry has long been a proponent of regenerative medicine. The use of calcium hydroxide for induction of reparative dentinogenesis and dentin bridge formation during vital pulp therapy has been a routine procedure for many decades, although our understanding of the mechanisms of action of this medicament has been limited. The identification of various bio-active molecules, including growth factors, sequestered in the dentin matrix has provided opportunities for their exploitation in dentin-pulp repair (reviewed in Smith and Lesot, 2001). Similar opportunities have also provided exciting possibilities for periodontal regeneration where guided tissue regeneration (GTR) and other approaches have been widely investigated (reviewed in MacNeil and Somerman, 1999). The non-vital nature of enamel in the erupted tooth provides us with greater challenges. This tissue, with its refined wear-resistant properties, is fundamental to oral function, and yet it is frequently the first to be lost. Remineralization of enamel has application in some circumstances, but innovative solutions are required to compensate for significant loss of this tissue. The exquisite prismatic structure of this tissue offers exciting opportunities for collaborative research between biologists and physical scientists. Clearly, the future for regenerative and tissue-engineering applications to dentistry is one with immense potential, capable of bringing quantum advances in treatment for our patients. The need for high-quality research in the basic sciences is paramount to ensuring that the development of novel clinical treatment modalities is underpinned by robust mechanistic data, and that such approaches are effective. This translational model epitomizes how dentistry should evolve and highlights the need for close partnerships between basic and clinical scientists. REFERENCES
Journal of Dental Research, Vol. 83, No. 7,
517 (2004)
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