A Glimpse into the Future: 23 Future Trends in Caries Research
Over the past three decades, the terms tissue engineering, nanotechnology, genetic engineering, probiotics, genomics, and proteomics have become increasingly familiar in the scientific literature. Cariology research has been somewhat slow in adapting these new technologies and techniques for preventing and treating what is one of the most ubiquitous of human diseases. However, “times they are a-changin’” in the world of cariology as we move away from the focus on invasive care (restorations) to one of caries control and its prevention. Our understanding of the etiology of caries has been expanded by using genomic strategies to probe the genetic contribution to caries susceptibility. The genetic engineering of noncaries-producing “cariogenic” bacteria and antibodies against cariogenic bacteria offers solutions to prevent acid production from plaque and the colonization by cariogenic bacteria. The ability to stimulate new dentin formation for repair of this tissue and the use of nanotechnology to manufacture synthetic enamel and smart materials will aid in the treatment of caries. Finally, proteomics and fluorescent images may help us solve the last great mystery in cariology: when is a carious lesion active?
Thus, in this chapter, promising approaches that in the future might be useful in the prevention and management of caries will be expanded upon and will cover:
Genetic susceptibility to caries
Carious lesion activity
Regeneration and repair of the dentin/pulpal complex
New restorative materials
Although the environmental and host factors which contribute to the risk of caries in individuals have been known for many years, there are still individuals who are more or less susceptible to this disease. Much of the evidence for a genetic contribution to the risk of caries has come from studies of twins reared apart. Dental caries has been examined in twin populations since early in the 20th century. In 1927, an evaluation of 301 pairs of twins was undertaken, of which 130 were monozygotic and 171 were dizygotic. The results of the study demonstrated that monozygotic twins had a similar caries incidence, but the dizygotic twins did not. This was later confirmed by other investigators, that the risk of caries in monozygotic but not dizygotic pairs of twins was similar.1
It has been estimated that the genetic contribution to the disease is about 40%. Dental caries is a complex disease, and like other complex diseases such as diabetes, osteoporosis, and cleft lip and palate, the knowledge gained from the human genome project does allow us to study genetics. Thus, the approach taken to identify the genetic contribution to an individual′s risk for caries has been similar to those used for other complex diseases. There are ongoing studies using DNA samples from caries-resistant and caries-prone siblings to detect SNPs (single-nucleotide polymorphisms) showing an association with caries resistance and caries susceptibility. The most likely candidate genes being pursued are those involved in enamel development and mineralization, salivary protein expression (especially the acidic-rich proteins), and dental hard tissue colonization by bacteria.
Probiotics—Replacement Therapy with non-Acid-Producing Bacteria
Our ability to genetically engineer bacteria makes it possible to “infect” tooth surfaces with bacteria that have the positive characteristics of metabolizing refined carbohydrates into urea rather than organic acids, and thus can fill the ecological niche at caries-susceptible sites with virulent but harmless bacteria. This may have greater implications when one considers the concept of the maternal fidelity of organisms, particularly mutans streptococci, during their passage from mother to offspring. This has intriguing possibilities in terms of prevention.
For example, if the mother were infected or reinfected with a “harmless” mutans streptococcus, which is non-acid-producing, and with the virulence to occupy the caries-susceptible sites, it would then be passed onto her child. It may, however, be difficult to convince the general public to accept a genetically engineered bacterium as a “cure” for a non-life-threatening disease. Therefore, naturally occurring bacteria that compete with cariogenic bacteria for the same ecological niche have been tested for probiotic therapy.2–4
Gene Therapy—Repairing Salivary Glands
The importance of saliva in the origin of caries is demonstrated most easily by the aggressive progression of the disease in its absence. Recent work, using gene therapy to repair salivary glands, will no doubt reap dividends in the future. It is important to understand that a gland has to be competent even if at a very low level. If it has been destroyed by disease or radiation, it cannot be rescued by gene therapy. This pioneering work has now progressed into human clinical trials, the results of which are eagerly anticipated. As yet, however, there is no easy solution to xerostomia, and the likely chance of it increasing in aging populations is significant, as older people will probably continue to make even greater use of drugs that have salivary flow-limiting side effects.5
Antibody Engineering—Bacterial Adherence
Recently, local passive immunization has aroused interest as a safe procedure in prevention of dental caries. New technologies for antibody engineering make possible the production of immunoglobulins in animals and transgenic plants (plantibodies). The murine IgG1 has been isolated and was effective against the streptococcal cell surface adhesion (SAI/II) protein, which mediates bacterial attachment to the salivary pellicle. This IgG1 antibody has been successfully evaluated in humans. After antibody therapy, the incidence of mutans streptococci was very much reduced. High-molecular-weight secretory immunoglobulin against mutans streptococci surface fibrillar adhesins (AgI/II) was produced by introducing cloned genes encoding the chains of monoclonal antibody against AgI/II, a murine J-chain and a rabbit secretory component, into a transgenic tobacco system (Nicotiana tabacum). The efficacy of this plant secretory antibody was studied on a small group of human volunteers and it was proven that the antibody was active for up to three days in the human oral cavity (two days longer than murine IgG antibody) and stimulated specific protection in humans against colonization by Streptococcus mutans for at least four months.