PLASMA MEDICINE - ONE OF THE EMERGING ROLE IN MEDICINE AND DENTISTRY

Plasma medicine emerged within the last decade as an exciting new field of analysis at the interface between physics and therefore the life sciences. 

Matter is usually composed of liquids, solids, and gases. 

A fourth element of matter has been delivered to notice that has been named plasma. 

Even though concern and anxiety might be managed; the needle pricks and the heat generated with drills are each painful and damaging to the tissues of the tooth. 

A replacement technology which might cut back the pain and destruction of the dental tissues are going to be of giant value. 

Not only plasma used in dentistry it is also used variety of medicinal uses such as

• Sterilization
• Wound healing
• Tumours
• Cancer 
• Drug delivery

Cold atmospheric pressure plasmas (CAP), however, also can be used for the treatment of viable tissues and therefore became a spotlight of medical research over the past years. 

Besides therapeutic applications, CAP is additionally used for surface modification and biological decontamination.

PLASMA

Physical plasma is outlined as a gas within which a part of the particles are present in ionising form. 

This is often achieved by heating a gas which ends up in the dissociation of the molecular bonds and afterwards ionization of the free atoms. 

Plasma consists of positively and negatively charged ions and negatively charged electrons in addition as radicals, neutral and excited atoms and molecules. 

Plasmas emit magnetism radiation, predominantly 

• Ultraviolet radiation
• Visual light
• Excited gas molecules
• Positively charged ions 
• Negatively charged ions
• Free electrons
• Neutral reactive oxygen/nitrogen species (ROS/RNS)
• Free radicals
• Molecule fragments. 

On the idea of relative temperatures of the ions, neutrals, and electrons, plasmas are classified as “thermal” or “nonthermal”. 

Electrons and serious particles of thermal plasma stay within thermal balance with each other. 

The electrons of nonthermal plasma (NTP) are hotter whereas ions and neutrals remain at area temperature. 

Recently, NTP sources with Non-thermal part Plasmas are very economical in the deactivation of bacteria. 

A comparatively new area is the use of those plasmas in dental applications. 

Photo credit: Laroussi M. Plasma Medicine: A Brief Introduction. Plasma. 2018; 1(1):47-60. 

COLD ATMOSPHERIC PLASMA

Cold atmospheric plasma (CAP) is additionally called NTP as a result of the presence of electrons and heavy particles at a really high temperature and room temperature. 

The temperature at the purpose of application is less than 104°F.

Plasma needle, dielectric barrier discharge, plasma pencil, and so on are getting used for the assembly of NTP. 

Wide applications of CAP in dentistry and medicine are rumored in recent literature considering its ability to kill cancer cells and deactivate numerous infective microorganisms.

Recent literature has shown the applications of CAP for sterilization of medical and dental equipment, packaging of food in the food industry, blood coagulation, promotion of wound healing, etc.

Low temperature plasma, additionally called cold plasma, is employed within the modification of biomaterial surfaces. 

It's characterized by an occasional degree of ionization at low or part pressure. 

Low temperature plasma is made by the conversion of a compound into gas followed by ionization by applying energy within the variety of heat, direct or alternating electrical current, radiation or laser light. 

Oxygen, nitrogen, element or celebration are the usually used plasma gas sources.

• Hardness
• Resistance to chemical corrosion 
• Physical abrasion
• Wettability
• The water absorption capability in addition because the affinity towards specific molecules is modulated specifically and exactly by the use of low temperature plasmas.

APPLICATION OF PLASMA IN MEDICINAL USES

IN WOUND HEALING

The use of a hand-held dielectric barrier discharge plasma generator (PlasmaDerm® VU-2010) to alleviate chronic venous leg ulcers has been assessed associate exceedingly in monocentric, two-armed, open, prospective, randomized, and controlled trial.

Accelerated wound healing has conjointly been discovered in a mouse model treated with a cold plasma jet.

There are many aspects of CAP which will contribute to an improved wound healing: 

• Ultraviolet radiation and reactive gas species (i.e., ozone) disinfect the wound
• Generation of nitric oxide (NO) or nitrogen species (NOx) stimulates the regeneration of tissue
• Current stimulates angiogenesis.
• Decrease of pH of the wound.

In cell culture experiments with HaCaT keratinocytes and MRC5 fibroblasts, an raised motility of the cells has been discovered after plasma treatment, and a minimum of in HaCaT cells, this was related to a diminished messenger RNA and protein expression of Cx43. Cx43 could be a gap junctional protein of keratinocytes and was shown to inhibit cell migration and wound healing. 

These findings suggest that cold plasma enhances wound healing in chronic and slowly healing wounds.

IN CANCER

Low temperature atmospheric pressure plasmas (LTP) to destroy cancer cells and tumors during a selective manner. 

Direct plasma applications to cancer cells and tissues, investigators reportable that plasma-activated media (PAM) may be wont to destroy cancer cells. 

Plasma-generated reactive species move with the contents of the medium and generate solvated durable reactive species within the liquid, akin to 

• Hydrogen peroxide (H2O2)

• Nitrite NO2−

• Nitrate NO3−

• Peroxynitrite ONOO−

• Organic radicals. 

In cancer cells, the mechanisms of action of LTP are suspected to be involving a rise of intracellular reactive oxygen species (ROS), which may result in cell cycle arrest at the S-phase, DNA double-strand breaks, and induction of programmed cell death. 

Analysis by varied groups showed that RONS generated by LTP react with cell membranes and might even penetrate the cells and induce ensuant reactions at intervals the cells that may trigger cell-signaling cascades, which may ultimately result in apoptosis in cancer cells. 

A single plasma treatment induced ablation of the neoplasm and diminished the expansion rate markedly. 

Detachment of SW900 cancer cells from the culture vessel when plasma treatment has been determined, whereas no detachment was observed when normal human bronchial epithelial (NHBE) cells were treated. 

The role of myeloid cells and also the immunogenic necrobiosis model of cancer treatment as potential mechanisms of action of CAP.

Cold plasma provides a possible variety to electrochemotherapy and could serve as a new choice for palliative skin melanoma therapy, either alone or together with electrochemotherapy.

IN ACTINIC KERATOSIS

The malignant tumor keratosis could be a patch of thick, scaly, or crusty skin. 

There are many options to treat actinic keratosis so as to stop the event of epithelial cell carcinomas. 

One choice is that the use of ingenol mebutate, that works in two ways: first, it ends up in rapid lesion necrosis starting one to 2 hours when application of ingenol mebutate, ensuing from mitochondrial swelling and membrane disruption still as membrane depolarization. 

This method causes an inflammatory response, which, subsequently, leads to specific neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) at interval days. 

These specific antibodies bind to specific antigens on abnormality epidermal cells, still on receptors of infiltrating neutrophils, thereby inflicting the discharge of cytotoxic agents (e.g., ROS), that then destroys abnormality dermal cells. 

CAP showed an attenuated request for pain medication, a discount of typical malodorous odor involving a reduction of microbial load, and in some cases even a superficial partial remission of growth and wound healing of infected ulcerations.  

Application of CAP as an innovative therapy for skin cancers or malignant tumor conditions, however the proof remains sparse, and more basic research as well as more clinical studies are needed. 

Photo credit: James Heilman, MD (Wikipedia commons) 

APPLICATION OF PLASMA IN DENTAL USES

IN DENTAL CARIES

A plasma needle is an efficient supply of various radicals that are capable of microorganism decontamination; however, it operates at temperature and thus, doesn't cause bulk destruction of the tissue. 

Plasma will treat and sterilize irregular surfaces; creating them appropriate for decontaminating dental cavities while not drilling. 

Although plasma itself is superficial, the active plasma species it produces can simply reach within the cavity.

Plasma treatment is actually a prominent tissue-saving technique that allows irregular structures and narrow channels within the diseased tooth to be cleaned. 

Short-lived chemical species in the gas phase produced by the plasma needle can interact on a tooth's surface such as enamel and can dissolve into a liquid. 

Dissimilar to the liquid rinses with bactericidal ingredients that stay in the oral cavity after the procedure, the plasma needle produces bacterial killing agents locally, which can reach the inside of the cavity and fissure spaces.

Non thermal plasma treatment is potentially a novel tissue-saving technique, allowing irregular structures and narrow channels within the dental caries tooth to be cleaned

IN WHITENING OF TEETH

NTP for teeth bleaching and incontestable that this result is due to the discharge of OH radicals and removal of surface proteins.

A non thermal, atmospheric pressure, noble gas plasma jet device was developed to boost the tooth bleaching effect of hydrogen peroxide (H2O2). 

Combining plasma and H2O2 improved the bleaching effectuality by an element of 3 compared with using H2O2 alone. 

Tooth surface proteins were perceptibly removed by plasma treatment. 

Once a piece of tooth was added to an answer of H2O2 as a catalyst, production of OH once plasma treatment was 1.9 times bigger than when using H2O2 alone. 

It's instructed that the improvement in tooth bleaching elicited by plasma is due to the removal of tooth surface proteins and to raised OH production. 

NTP was the foremost effective in tooth bleaching while not inflicting any damage to the tooth other than urea peroxide alone and a combination of carbamide peroxide and diode laser. 

The combination of plasma treatment and bleaching removed most of the blue-stains. 

It had been complete that vacuum plasma pre-treatment and bleaching showed promise as some way of removing blue-stain.

IN ORAL CANDIDIASIS

Oral candidiasis includes Candida-associated denture stomatitis, angular stomatitis, median rhomboid glossitis, and linear gingival erythema. 

Stomatitis caused by Candida albicans can be cured by plasma jets. 

IN DENTAL RESTORATION (DENTAL COMPOSITE)

plasma modifies the dentin surface and will increase dentin/adhesive surface bonding with that interface-bonding enhancement to considerably improve composite performance, durability, and longevity.  

Mechanical ways may be a supermolecule layer, the questionable “smear layer,” that is primarily composed of type I collagen that develops at the dentin/adhesive junction. 

To form a porous surface that the adhesive will infiltrate, current preparation techniques etch and demineralize dentin. 

Interactions between demineralised dentin and adhesive provides rise to the smear layer, which truly inhibits adhesive diffusion throughout the prepared dentin surface. 

This protein layer is also responsible, in part, for inflicting premature failure of the composite restoration. 

It contributes to inadequate bonding which will leave exposed, unprotected collagen at the dentin- adhesive interface, permitting microorganism enzymes to enter and more degrade the interface and therefore the tissue Dental composite restoration for improved interface properties and their results showed that Atmospheric cold plasma brush (ACPB) treatment can modify the dentin surface and so increase the dentin/adhesive surface bonding. 

NTP can alter the surface characteristics of dentin, which ends up into inflated bonding between dentin and adhesive restorations.  

Plasma treatment of fiber-reinforced composite and resin composite have more tensile shear bond than ancient core build up.

Dental composite

PLASMA IN STERILIZATION

Non-thermal atmospheric plasmas,” permits surface preparation in open air at room temperature. 

One in every of the necessary options of non-thermal plasma is the abundant production of reactive species in low gas temperature which incorporates charged particles, radiation, and reactive oxygen species. 

The complicated elements from non-thermal plasmas succeed in multi-functional treatment in the oral cavity. 

Reactive oxygen species and reactive element species are considered a key factor for sterilization, wound healing, and tooth whitening. 

Heat kills bacteria, however the applying of this method to living tissues is dangerous. 

Sterilizing agents or antibiotics are wont to treat human tissues that are infected by pathogens, however might result in pain and antibiotic resistance. 

Recently, non-thermal atmospheric plasmas are shown to be extremely efficient at killing microorganisms in a reasonable manner; therefore, the employment of such plasmas could eliminate the issues associated with use of heat and antibiotics. 

Plasma consists of a variety of various elements that all may contribute more or less to its efficaciousness. 

Whereas the mechanisms for the efficacy of CAP aren't totally understood, it's conceivable that physical components like ultraviolet radiation radiation or electrical current moreover as chemical components such as reactive oxygen species or reactive nitrogen species play a role within the mode of action. 

CAP used as disinfection (bacteria, fungi, and viruses). 

NTP device for sterilization of varied instruments and equipment fabricated from metals, rubbers, and plastics. 

It was found that NTP device was extremely efficacious in deactivation of both Bacillus subtilis and E. coli and was stiffer in killing E. coli than the UV sterilizer. 

A two-minute CAP treatment has been shown to be effective against a range of microorganism as well as important skin and wound pathogens such as 

• Escherichia coli
• Group A Streptococcus
• Methicillin-resistant staphylococcus aureus (MRSA)
• Pseudomonas aeruginosa

suggesting positive effects of CAP on wound healing. 

A vital reduction of microorganism and fungous targets after plasma treatment has conjointly been shown on model nails with onychomycosis (a fungal infection of the nail). 

Autoclaves and UV sterilizers presently want to sterilize dental instruments. 

To develop a dental sterilizer which might sterilize most materials, like metals, rubbers, and plastics, the sterilization impact of an atmospheric pressure non-thermal air plasma device was proven that the atmospheric pressure nonthermal air plasma device was effective in killing both 

• Escherichia coli 
• Bacillus subtilis

and was more practical in killing Escherichia coli than the UV sterilizer. 

The plasma can be touched by bare hands and directed manually by a user to put it into the root canal for disinfection while not inflicting any painful sensation. 

Once He/O2(20%) is employed as operating gas, the motion and vibrational temperatures of the plasma are concerning 300 K and 2700 K, respectively. 

The peak discharge current is about ten mA. 

Preliminary inactivation experiment results showed that it can expeditiously kill Enterococcus faecalis, one among the most types of microorganism causing failure of root-canal treatment. 

Cold plasma had a high efficiency in disinfecting the Enterococcus faecalis biofilms in vitro dental root canal treatment.

PLASMA IN MEDICAL AND DENTAL IMPLANTS

have aimed at reducing restenosis after implantation of vascular stents, which now, can be achieved at ease by plasma based approach.

Plasma has also found its applications in the coating of implants with antithrombogenic agents with regard to the vascular prostheses and stents which are in constant contact with blood. 

Thrombosis and blood clot formation are severe and potentially life-threatening complications in such cases. 

Classical anticoagulants used for thrombosis prophylaxis and treatment include coumarin derivatives like phenprocoumon for oral application as well as heparin for parenteral use. 

The Plasma-based attachment of heparin has been examined for stainless steel which is used in stents. 

Owing to their well-known antibacterial effects, metals like silver, copper or tin are possible alternatives to classical antibiotic compounds as an effective and sustained release from coatings is possibly easier to achieve due to their small size. 

Similarly to gentamicin as mentioned before, silver has been used as a powder added to a plasma-sprayed wollastonite coating on titanium implants. 

Similarly, the use of copper for antibacterial implant coatings has also been studied by plasma implantation into polyethylene. 

Compared to controls, the implants created by this Plasma immersion ion implantation of copper reduced the number of methicillin resistant Staphylococcus aureus cultivated on the respective surfaces. 

Ion implantation can also be used for non-metals like fluorine which is of particular relevance for dental applications. 

This was examined with titanium, stainless steel and polymethyl methacrylate for fluorine alone or with stainless steel for a combination of fluorine with silver. 

Plasma treatment also aids in the application of therapeutic agents onto implant surfaces as well to achieve their controlled release over time. 

Plasma processes can be used for surface coupling of antibiotic substances or for integration of metal ions into biomaterial surfaces to create implants which exhibit long-lasting antibacterial properties after implantation thereby, the often devastating effects of implant-related infections could be markedly reduced.

The possible applications are drug-eluting stents and vascular prostheses which release drugs to reduce blood coagulation and thrombosis as well as to prevent intima hyperplasia and restenosis.

DENTAL IMPLANT

Photo credit: Coronation Dental Specialty Group (Wikimedia Commons)

RIGHT FOREARM IMPLANT

Photo credit: Fremry at English Wikipedia (Wikimedia Commons)

CONCLUSION

CAP against various cancer entities, suggesting plasma to be a potential new therapy against numerous cancerous diseases. 

The exciting field of plasma remedy is increasing and therefore is supplying increasing evidence for the usage of CAP as a treatment choice for a variety of diseases. 

Plasma dental treatments are painless and drill-less, thereby making them patient-friendly, specifically in children and under-served communities, wherein communities, education, and familiarity with the dentist's chair are, by definition, limited. 

The plasma therapy may function as an exceedingly valuable device amongst pedodontists and as well as dentists in less-serviced communities, wherein individuals do not readily obtain proper dental care. 

However, to integrate plasma treatment into trendy cancer therapy, further studies need to be conducted.

REFERENCE

• Kumar Ch S, Sarada P, Reddy Ch S, Reddy M S, Dsv N. Plasma torch toothbrush a new insight in fear free dentisry. J Clin Diagn Res. 2014;8(6):ZE07-ZE10. doi:10.7860/JCDR/2014/8815.4516.
• Bernhardt T, Semmler ML, Schäfer M, Bekeschus S, Emmert S, Boeckmann L. Plasma Medicine: Applications of Cold Atmospheric Pressure Plasma in Dermatology. Oxid Med Cell Longev. 2019;2019:3873928. Published 2019 Sep 3. doi:10.1155/2019/3873928.
• Bekeschus S, Schmidt A, Niessner F, Gerling T, Weltmann KD, Wende K. Basic Research in Plasma Medicine - A Throughput Approach from Liquids to Cells. J Vis Exp. 2017;(129):56331. Published 2017 Nov 17. doi:10.3791/56331.
• Ranjan R, Krishnamraju PV, Shankar T, Gowd S. Nonthermal Plasma in Dentistry: An Update. J Int Soc Prev Community Dent. 2017;7(3):71-75. doi:10.4103/jispcd.JISPCD_29_17.
• Laroussi, M. Plasma Medicine: A Brief Introduction. Plasma 2018, 1, 47-60.