The Future Looks Bright

Plasma medicine refers to a new field of multidisciplinary research involving the biomedical applications of plasma—an ionized gas. Since the 1990s, researchers have been investigating novel ways to use low temperature atmospheric pressure plasma (LTAPP) to inactivate a broad spectrum of microorganisms and accelerate wound healing.^1-4 Recent discoveries in plasma science include treating skin disorders such as diabetic ulcers; eradicating tumors; and cosmetic skin rejuvenation.^5-7 LTAPP applications are now making a lateral transition to dentistry for use in sterilization and disinfection, inactivation of oral pathogens, and enhanced tooth whitening.

Low Temperature Atmospheric Pressure Plasma

The universe contains four states of matter: solid, liquid, gas, and plasma (Figure 1). Plasma occurs naturally and comprises 99% of the visible world. Plasma is a gas mixture of charged ions and electrons that are activated by energy, such as electricity. Plasma is found in the sun, lightening, neon and fluorescent light bulbs, and televisions. There are two categories of plasma: thermal and nonthermal. Thermal plasmas are hot to the touch and require pressure and a significant power source to operate. Nonthermal plasma is artificially generated using ambient air, and it requires much less power to function. LTAPP is particularly relevant to medicine and dentistry because it is simple to manipulate and can be applied directly to the skin without causing cellular damage.^8,9

Several devices have been designed for medical and dental applications. The LTAPP plasma pencil (Figure 2), developed by Laroussi et al, is a handheld device that resembles a miniature lightsaber. It emits a plasma plume that can deliver direct nonthermal plasma to a target, and remain stable for several hours without damaging human tissue (Figure 3).⁹ LTAPP is effective in the inactivation of numerous pathogenic microorganisms, including: Geobacillus stearothermophilus, Bacillus cereus, Streptococcus mutans, Porphyromonas gingivalis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Aspergillus niger.^10-14 Although the mechanism of action is not clearly understood, research suggests that LTAPP exposure either disturbs or destroys cell membranes or renders cells unable to reproduce.

Sterilization

Current sterilization methods in dentistry include steam, dry heat, and the use of chemicals, such as ethylene oxide. These techniques are slow, energy inefficient, and can be toxic to humans and the environment. In some instances, repeated use of heat and chemicals can damage instruments and equipment. As a result, other sterilization methods are in demand, and LTAPP may provide such an alternative.

The gold standard in evaluating the effectiveness of heat sterilization is the use of biological indicator test strips containing G. stearothermophilus and B. cereus. Both microbes are heat resistant at the spore stage.^15,16 B. cereus is often associated with food poisoning, and G. stearothermophilus is an appropriate yardstick for measuring bacterial destruction. When LTAPP was used on both organisms, the vegetative states of each organism and the spore state of B. cereus were completely destroyed. Spores of G. stearothermophilus, however, were not completely eliminated.¹⁶ Modifications of the cold plasma device to improve its success in G. stearothermophilus spore destruction are ongoing.

Caries

The prevalence of S. mutans is evident in nearly all populations across the globe,¹⁷ and caries remains one of the most common chronic, transmittable, destructive—yet preventable— diseases. Contemporary caries prevention methods include the use of fluorides and mechanical biofilm removal, but optimal plaque control is not always achieved. Restorative treatment requires removing the infected tooth structure, as well as healthy tooth structure, and replacing lost structure with metal or composite. A more advantageous proposal for the management of dental caries may be to destroy the key causative agent—S. mutans—leaving healthy tissue intact. Several studies have shown that nonthermal plasma has the ability to destroy or inactivate S. mutans.^18-22 A recent study found that the plasma pencil inactivated S. mutans in as little as 60 seconds.²⁰ The application of LTAPP to S. mutans for various intervals demonstrated significant bacterial inactivation.^18-22 Given that LTAPP has a time/dose response effect and is capable of penetrating small areas, applying it to enamel pits and fissures may reduce ccaries-causing microorganisms.

Periodontal Pathogens

Periodontal diseases are chronic oral infections caused by several anaerobic periodontal pathogens, including P. gingivalis. Research has found that periodontal diseases affect overall systemic health, making their effective treatment imperative.²³ Periodontal diseases are traditionally treated with the removal of pathogens through scaling and root planing and locally or systemically delivered chemotherapeutic agents.²⁴ Neither of these methods sustains long-term control of periodontal pathogens, and they may not reach the base of deep pockets. A recent study suggests that LTAPP is capable of inactivating P. gingivalis. Results showed that the ability of LTAPP to inhibit bacteria increased the longer it was employed.²⁵ Because LTAPP can be targeted in a confined space, it may have potential as a site-specific treatment to inactive periodontal pathogens and accelerate wound healing.

Tooth Whitening

Tooth whitening is one of the most requested dental procedures—most patients want whiter teeth and a more esthetic smile. Yet, whitening procedures are time consuming and often cause dentinal hypersensitivity and mucosal irritation. Typically, in-office tooth whitening procedures require the use of relatively high percentages of hydrogen peroxide, ranging from 25% to 35%, and some type of accelerator light. In an effort to develop alternative methods of tooth whitening, researchers are studying the effects of LTAPP as a light source to augment the whitening process (Figure 4). Literature supports the theory that tooth whitening is enhanced by using LTAPP with a peroxide gel, compared to using peroxide alone.^26–30

During the whitening process, hydrogen peroxide breaks down to produce hydroxyl radicals. Accelerant lights speed up this oxidation process, which ultimately reacts with organic and inorganic compounds and leads to whitening. Although the plasma-whitening relationship is not well understood, researchers theorize that LTAPP enhances the production of reactive oxygen hydrogen radicals.

Studies show that the amount of oxygen hydrogen generated from hydrogen peroxide improves whitening after various time exposures,²⁶ and the use of plasma with hydrogen peroxide increases the production of reactive oxygen hydrogen radicals.²⁹ When compared to using hydrogen peroxide alone, plasma was more successful in lightening coffee and red wine stains in extracted teeth.²⁹ Additional research shows that plasma-enhanced whitening occurs without thermally damaging the tooth or altering morphology or microhardness.²⁹ In a recent study that used the LTAPP pencil, whitening occurred in as little as 10 minutes.³⁰ LTAPP’s role in tooth whitening has yet to be defined, but foundational studies suggest it can safely enhance the tooth-whitening process.

Future Research

LTAPP is currently being investigated for use in endodontic therapy.³¹ Generally, root canal disinfection is accomplished through the use of sodium hypochlorite and other antimicrobial agents. Researchers are experimenting with plasma as a root canal disinfectant because of its ability to navigate cracks, crevices, and convoluted areas. If LTAPP applications are successful, it could reduce failed endodontic treatment.

LTAPP has proven successful as a surface modification agent in other industries, such as food safety. Food packages are treated with plasma in an effort to reduce pathogenic microorganisms from adhering and proliferating in containers.³² The interactions of plasma-treated surfaces are complex, yet research has shown that areas treated with LTAPP prevent bacterial adherence and microbial colonization.³² In dentistry, the application of a plasma layer to an implant may inhibit biofilm adherence and growth that could contribute to reducing periimplant disease.³³ Additionally, treating dental materials, enamel, or dentin surfaces with LTAPP may enhance adhesion for certain types of restorations.

Plasma has demonstrated success in wound and tissue healing, hence the leap to treating oral lesions is a natural one. Plasma may assist the curative process by inactivating pathogenic microorganisms while leaving healthy cells intact. In dentistry, common oral diseases, such as candidiasis, apthous ulcers, herpetic lesions, as well as infected extraction and periodontal sites, may benefit from the therapeutic effects of LTAPP. Employing plasma to combat opportunistic infections would be an alternative to present-day mechanical, chemical, and antimicrobial management.

Conclusion

The future of plasma medicine is promising and the potential is tangible. Plasma applications range from water treatment, sterilization and disinfection, inactivation of environmental and oral pathogens, wound healing, surface modification, and tooth whitening. Plasma science represents a shift away from chemical and mechanical therapies to those that are molecular based. The cooperation between specialists in medicine, dentistry, engineering, chemistry, physics, and microbiology has created an innovative specialty. Proof-of-concept research demonstrates the ability of plasma’s biomedical applications to segue into dentistry.

Acknowledgement

The authors would like to thank Mounir Laroussi, PhD, director of the Laser and Plasma Engineering Institute at Old Dominion University, for his expertise and assistance with plasma research.

PHOTO CREDITS

FIGURE 1. COURTESY OF GAYLE B. MCCOMBS, RDH, MS, AND DONALD K. EMMINGER

FIGURE 2. CHARLES E. THOMAS

FIGURE 3. CHARLES E. THOMAS

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From Dimensions of Dental Hygiene. December 2011; 9(12): 40-43.