INTRODUCTION:

Pulpotomy is defined as the removal of the coronal portion of the dental pulp followed by placement of the suitable dressing or the medicament which will promote healing and preserve the vitality of the teeth in the dental arch¹. Formocresol was introduced by Buckley in 1904. It was used for the treatment of non-vital permanent teeth. Its use in primary molars was not advocated until 1930. It was re-emphasized by Sweet in 1930, who proposed the multiple visit formocresol technique. This technique involves placing the formocresol in contact with the radicular tissue for long periods of time i.e. 2-3 days to mummify the tissue completely. When completely fixed, the radicular pulp was sterilized and devitalized avoiding infection and internal resorption. Later it was reduced to three visits¹. However, sweet reduced the number of visits over the years, presumably because of economic and behavior management considerations. Since, 1960's a single visit procedure has been advocated.

This procedure used 19% formaldehyde to produce fixation of the pulp tissue².Various modifications have been tried regarding the techniques used for FC pulpotomy and the concentrations³. It was proposed that zinc oxide eugenol should be placed in direct contact with the pulp stump prior to the placement of the final restoration⁴. In a histological analysis, they found that the histology of the pulp tissue was unaltered by prolonged application of formocresol following 5-minute procedure.

Buckley’s formocresol includes formaldehyde 19%, Cresol 35%, glycrerine 15%, and water with an approximate pH of 5.1. Currently 1:5 dilution of Buckley’s formocresol is commonly used. A diluent consists of 3 parts of glycerine (90 ml) added to one part distilled water (30 ml). Later 4 parts of diluent (120 ml) is mixed with one part of Buckley’s FC (30ml) pulpotomy⁵. Commercially available products vary in concentrations of their ingredients, for example Sultan formocresol available in India consists of 48.5% formaldehyde, 48.5% cresol and 3% glycerine. Several studies have been investigated regarding the effects of various concentrations of formaldehyde from a 35% solution, 19% formaldehyde in Buckley's formulation, to a 1:5 dilutions.

MECHANISM OF ACTION:

Formocresol acts as a potent bactericidal and devitalizing agent. Formocresol prevents the tissue autolysis through bonding of the aldehyde group of formaldehyde to the side chains of the amino acids of both the bacterial proteins and the remaining pulp tissue. It is a reversible process without changing the basic structure of protein molecule⁶. It converts the microorganisms and the remaining vital pulp tissue into inert compounds⁷. According to Massler et al., 1959 when the formocresol is placed in direct contact with the pulp for a period of 7 to 14 days, there is a zone of fixation occurring immediately below the medicament where it is placed⁸. At the amputation site, coagulation necrosis occurs due to denaturing of the proteins in the cells⁹. This is due to the reduced activity of oxidative enzymes in the pulp tissue⁷.

In the middle third it produces a pale staining zone of poor cellular definition and necrosis. Apically there is a zone of chronic inflammation, which blends into normal tissue.¹⁰ There was complete loss of vitality in the apical third of the root canal¹¹. Polymorphonuclear cells (PMNs), when exposed to formocresol in low concentration causes stimulation of the PMN cells contributing to the chronic inflammatory change¹². It also have an effect on hyaluronidase action. The pulp tissue is fixed by binding to the proteins through inhibition of the enzymes to render it inert and resistant to enzymatic breakdown⁷.

SYSTEMIC AND ADVERSE EFFECTS OF FORMOCRESOL:

Studies have shown formocresol therapy to have a clinical success rate between 70% and 90%.¹³ Concern has existed for the past decade regarding the safety and efficacy of formaldehyde-based medicaments like formocresol in dentistry. However, in June 2004 International Agency for Research on Cancer (IARC) classified formaldehyde as carcinogenic to humans. The three areas of concern regarding FC are its mutagenicity, carcinogenicity and immune sensitization. It has the potential to cause leukaemia and nasopharyngeal carcinoma. National Institute for Occupational Safety and Health in USA reported that if formaldehyde is exposed to a concentration of 20 ppb (parts per billion) or higher, it is instantly dangerous to health. Cresol in FC causes descruction of the vital tissue but when used as a pulpotomy medicament, the adverse effect is negligible¹⁴.

WHO stated that after one pulpotomy using 1:5 dilutions formocresol in a cotton pellet which is squeezed dried is approximately 0.02-0.10 mg¹⁵.

Morawas et al., 1975 has recommended 1:5 dilution of formocresol with glycerine and water for pulpotomies, which is based on the study by Loos et al., 1973 which showed that full strength formocresol may causes damage to the connective tissue¹⁶. However, 1:5 dilution of formocresol creates similar metabolic effect as full strength formocresol^17,18.

Histological studies reported that inspite of its good clinical success, chronic inflammation and necrotic tissue was observed¹⁹. Formaldehyde has the potential to be absorbed systemically after pulpotomy when used in high concentration. In an animal study in 1980 reported that up to 10% of the formaldehyde after formocresol pulpotomy was absorbed systemically in dogs²⁰.

Ranly DM, 1984 calculated the formocresol concentration when used as a pulpotomy medicament and reported that 300 pulpotomy has to be done in same individual to reach the toxic levels of formocresol.²⁰

A number of animal studies have demonstrated that chromosomal as well as carcinogenic alterations in epithelium occur due to the exposure to formocresol²¹.

Formaldehyde has been shown to be distributed systemically after pulpotomy. Up to 10% of the formaldehyde was absorbed systemically in dogs following formocresol pulpotomy¹⁹.

In 1985, animal study reported that following formocresol pulpotomy, radioactively labelled formaldehyde was seen distributed throughout the viscera of rats²².

Another study by Block RM et al., 1985 stated that when pulpotomy using formocresol was performed, it caused the formation of antibodies leading to immune sensitization in an animal model²³.

Kerns et al., 1983 found a relationship between development of squamous cell carcinoma when rat pulp tissue was exposed to formocresol²⁴. Formaldehyde was strongly associated with leukaemia leading to nasopharyngeal carcinoma²⁵.

Dentigerous cyst was also found to be associated with formocresol pulpotomy²⁶. In a study done in 2008 evaluating the blood samples immediately before and after 24 hours after formocresol pulpotomy, there was no statistical significant difference seen between the two groups in terms of chromosomal aberrations, chromatid breaks or chromatid gaps and therefore concluded that formocresol is not mutagenic²⁷. There was presence of enamel defects of the underlying successors when systemically absorbed in a primary teeth treated with formocresol^28,29.

Thus only the minute quantity of formaldehyde used for a period of 5 minutes in pulpotomy do not cause carcinogenic effects in humans and it is considered insignificant.

ALTERNATIVE PULPOTOMY MEDICAMENTS TO FORMOCRESOL:

CALCIUM HYDROXIDE:

Calcium hydroxide was introduced by Herman in 1920³⁰. The mechanism of action is through precipitation of calcium and phosphate. Calcium hydroxide has potent antibacterial property through the release of the highly reactive hydroxyl ions which cause destruction of the bacterial cytoplasmic membrane, protein lysis and bacterial DNA damage. It is effective against most endodontic pathogens³¹. It has the ability to form complete dentinal bridge and retains healthy radicular pulp³². The major drwawback of calcium hydroxide is the occurrence of internal resorption, which is believed to be due to the presence of clot intervening between the material and the pulp tissue producing chronic inflammation, which inturn stimulates the osteoclastic cells causing resorption.³³ Several clinical studies comparing calcium hydroxide with formocresol as a pulpotomy medicament showed less clinical and radiographic success rate with calcium hydroxide^33,34.

FERRIC SULPHATE:

Ferric sulphate (Fe₂ (SO₄₎3), is a chemical compound used as a pulpotomy medicament due to its astringent and styptic properties³⁵. Ferric sulphate is available as a 15.5% solution (Astringedent TM, Ultradent Products, Inc., Salt Lake City, UT), has been used commonly as a coagulative and homeostatic agent in pulpotomy and it is slightly acidic. The mechanism of action of ferric sulphate is still debated, but agglutination of blood proteins results from the reaction of blood with both the ferric and sulphate ions. When ferric sulphate is applied on to a cut blood vessel, the blood proteins get agglutinated. Red blood cells have sialated glycoproteins embedded which gives it a negative charged surface. This negativity will create a repulsive electric zeta potential between cells. When agglutination force exceeds the force of repulsive force generated by the negative charge, blood gets agglutinated.

Ferric and sulphate ions react with the blood and form agglutinated blood proteins. The agglutinated proteins forms plug which helps in sealing the capillary orifices thereby preventing clot formation. This could be due to chance that metal protein clot formed at the surface of pulp stumps can act as barrier and it minimizes the chances for chronic inflammation³⁶.

Most common pathology observed in ferric sulphate pulpotomy is internal resorption and calcific metamorphosis. This could be due to a result of the sub-base like ZOE used, which comes in contact with the highly perfused environment of pulp and undergo hydrolysis of the zinc eugenolate and releases free eugenol. It produces moderate to severe inflammatory response with resulting chronic inflammation, necrosis and leading to the formation of granulation tissue. Calcific Metamorphosis is due to metaplasia of connective tissue and macrophages to form osteoclast-like giant multinuclear odontoclasts³⁷. The clinical success rate was very high in both experimental groups (FC and FS). Radiographically, the overall failure rates for FC and FS were 6.2% and 8.3%, respectively. No hypoplastic or hypocalcified areas were observed in all succedaneous teeth replacing those primary teeth that received pulpotomies. There was no delay in the eruption of premolars under the pulpotomized teeth utilizing either pulpotomy specialists. Ferric sulfate is prescribed as a non-dangerous puloptomy medicament to supplement formocresol.

Recently a study done in 2017, which evaluated the clinical and radiographic findings of ferricsulphate and Biodentine pulpotomy. Biodentine showed superior clinical and radiographic success compared to ferric sulphate. They stated that ferric sulphate produces more inflammation comparably and Biodentine has the potential to form dentin bridge formation^38.

GLUTARALDEHYDE:

Gravenmade S 1975 introduced glutaraldehyde (GH) as a new pulp fixative agent. At ph of 7.5 to 8.5, it has a potent bactericidal effect. It is an aldehyde with higher fixative property compared to formocresol and noted that increasing the concentration and longer time improves fixation and suggested the use of 4% Glutaraldehyde for 4 minutes or 8% Glutaraldehyde for 2 minutes. It has less penetration into the suuronding periapical tissue by forming protein linkage. The systemic distribution of glutaraldehyde is limited

It does not diffuse laterally or apically, thus making it a safe substitute to formocresol as a pulpotomy medicament³⁹.

The main disdadvantage is that, it has a short life span of 14 days and needs to be ftreshly prepared. (Ranly DM et al., 1984) Glutaraldehyde produces inadequate fixation of the pulp tissue and it forms a deficient barrier susceptible for sub base irritation when used with zinc oxide eugenol leading to internal resorption³⁹. Long-term (36 months) success rates of four different glutaraldehyde preparations (2%- buffered and unbuffered, 5%-buffered and unbuffered) as a pulpotomy agent in pulp exposed primary molars were evaluated. The 5% buffered solution group showed highest success rate, whereas 5% unbuffered solution showed the lowest ⁴⁰.

In 2013, clinical study compared FS, FC and 2% Glutaraldehyde as a pulpotomy medicament. It reported that there was 100% clinical success rate and 83.3% radiographic success and concluded that GH can be recommended as an effective medicament alternative to FC and FS⁴¹.

ZINC OXIDE EUGENOL:

It is the first medicament used in preservation pulpotomy. Histological analysis done by Magnusson et al., 1971 reported that when zinc oxide eugenol was used as a pulp dressing material, there was inflammation and internal resorption associated with it⁴². Eugenol is said to possess destructive properties and cannot be placed directly on the pulp²².

In a clinical study done in 2013, there was 94% clinical success in ZnOE pulpotomy when compared with FC. Furcation radiolucency was observed most frequently in ZnOE group⁴³.

ELECTROSURGERY:

Electrosurgery was used in dentistry to remove soft tissue and to control haemorrhage associated with the surgical procedures. Electrosurgical (ES) pulpotomy is a nonpharmacological technique⁴⁴.

It was introduced by Anderman, 1982 who stated that it is a time efficient method and free of producing post operative complications. Mechanism of action behind ES pulpotomy is that when the electric arc placed 1 to 2mm above the pulp stump, it carbonizes and denatures the pulp leading to coagulation necrosis⁴⁵. Electrosurgery leads to good visualization and homeostasis and is less time consuming than the FC pulpotomy technique ⁴⁶. Study in 1987 compared ES and FC as a pulp dressing material. ES showed pathological root resorption and furcal pathology⁴⁷. High inflammation of the pulp tissue will not allow the penetration of the current, the success of ES depends on the initial status of the pulp and ES cannot eliminate the inflammation of the radicular pulp ⁴⁵.

In 2006, clinical trial was performed evaluating the clinical and radiographic success of ES and showed 100% clinical and 84% radiographic success⁴⁸.

Bahrololoomi Z et al., 2008 compared ES and FC. ES showed higher success rates than formocresol⁴⁹. In 2016, ES showed similar success rates when tested with formocreso ⁵⁰.

LASER:

Laser was introduced in dentistry in early 1960’s⁵¹. was the first to advocate the use of carbon dioxide laser on pulp in dogs and reported that there was controlled haemorrhage and there was no damage to the radicular pulp tissue seen histologically.

It has hemostatic, antimicrobial and cell stimulating properties. Pulp when irradiated with laser, creates a superficial zone of coagulation necrosis. Saltzman et al., 2005 in a study used diode laser and achieved hemostasis, but reported less radiographic success compared to formocresol pulpotomy⁵². Liu et al., 2006 compared Nd Yag laser with FC and reported that laser was highly successful than FC. Many studies are required in the literature with long term follow up to potentiate its use as an ideal pulpotomy medicament⁵³.

MINERAL TRIOXIDE AGGREGATE:

MTA was introduced by Torabinejad M is a bioactive material for root perforation at loma linda University in 1993⁵⁴. MTA was approved by the U.S. Food and Drug Administration for endodontic use in 1998. It is mainly composed of dicalcium silicate, tricalcium silicate, tricalcium aluminate, tricalcium oxide, tetracalcium aluminoferrite and bismuth oxide. They are made up of fine hydrophilic particles that solidify in the presence of moisture or blood⁵⁵. MTA has excellent sealing ability, biocompatibility, good compressive strength, insoluble in fluids once set⁵⁴.

MTA was prepared by mixing powder with sterile distilled water in a 3:1 ratio. On hydration

the particles in the powder forms a colloidal gel that solidifies to form hard barrier.

Setting time is affected by factors like moisture and air entrapped during trituration⁵⁶.

MTA is used in pediatric dentistry as a pulp capping agent, for pulpotomy in primary teeth, apical barrier formation for teeth with necrotic pulps and open apexes, perforation repair, and apexification in the permanent teeth⁵⁷.

The mechanism of dentinal bridge formation is that when MTA is used as a pulp dressing agent it induces cytologic and functional changes within pulpal cells, resulting in formation of reparative dentin at the surface of dental pulp. It causes proliferation, migration and differentiation of odontoblast-like cells that produce a collagen matrix. This formed unmineralized matrix is then mineralized by osteodentin initially and then by tertiary dentin formation.

Clinical trials have revealed that MTA’s performance is equal or superior to formocresol (FC), ferric sulfate, and might be considered as one of the favored pulpotomy materials⁵⁸. In a study done in 2011 comparing MTA with ferric sulphate (FS) pulpotomy for 6 months. There was 100% clinical success in both the groups. Radiographic success was 85.71% for the MTA and 83.33% for FS⁵⁹. The clinically-favorable pulpotomy response of MTA was attributed to bactericidal property, sealing ability and low toxicity of MTA.

BIODENTINE:

It is tri-calcium silicate based cement developed for use in various applications in dentistry. The calcium silicate in Biodentine reacts with water to form set cement. The hydrated calcium silicate (CSH) gel is formed along with calcium hydroxide as a byproduct⁶⁰. In contact with phosphate ions, it forms a precipitate that resembles hydroxyapatite.

It is most widely used as a pulp dressing material due to its faster setting time, high biocompatibility, high compressive strength, excellent sealing ability, and ease of handling without causing staining of the treated teeth⁶¹. It is proved to have an excellent antimicrobial property due to its very high alkaline PH(pH=12). It might be used as a promising alternative to other pulpotomy materials for dentin-pulp complex regeneration.

Sirohi K et al., 2017 compared FS with Biodentine as a pulpotomy medicament for 9 months. There was 96% clinical success rate in the FS group and 100% in the Biodentine group. Radiographic success rate in the FS group was 84%, whereas 92% in the Biodentine group but there was no statistical significant difference found between the two groups⁶².

HERBAL ALTERNATIVES–NEWER ADVANCES:

The need for finding newer herbal materials to replace standard pulpotomy materials is increasing recently. The use of herbal medicine for treatment of various infections is practiced in India since many years. The study of herbal medicine for the management of diseases is known as ethnopharmacology. The major advantage of using herbal alternatives are easy availability, cost effectiveness, increased shelf life, low cytotoxicty and lack of microbial resistance. The herbal medicaments so far tested in primary teeth as a pulpotomy medicament are

Aloe Vera, Allium Sativum, Ankaferd Blood Stopper, Propolis and Elaegnus Angustifolia

ALOE VERA:

Aloe Vera belongs to Liliaceae family. It grows mainly in the tropical, dry regions of Africa, Asia, Europe and America. In India, it is found in Rajasthan, Andhra Pradesh, Gujarat, Maharashtra and Tamil Nadu. Aloe Vera (Aloe barbadensis) is a kind of plant that is well known for its numerous biologic and therapeutic functions such as wound healing, hypoglycemic effects, anti inflammatory and immune-modulation features and also antimicrobial properties⁶³.

The Aloe Vera leaf is composed of two layers, the outer layer or rind contains vascular bundles and the inner colorless aloe gel which contain viscous clear liquid and 99.5% water. It is rich in essential amino acids which is required for smooth functioning of complex enzyme system in our body. It also contains vitamins, minerals, enzymes, polysaccharides, phenolic compounds and organic acids.Aloe vera is rich in vitamin A, vitamin B, niacin, riboflavin, choline and folic acid along with traces of vitamin B_12. It also has aluminium, sodium, potassium, calcium, magnesium, manganese, copper, zinc, chromium and iron⁶⁴. Aloe Vera is proved to have an anti-inflammatory, antibacterial, antifungal, antiviral, wound healing and analgesic property. It also exhibits excellent antioxidative property. It is commonly used in the treatment of skin burns and wounds⁶⁵.

It has wide applications in dentistry such as treating aphthous ulcers, lichen planus, in the treatment of gingivitis, periodontitis and in healing of the extraction socket. It has potent antiseptic property, which is used in the treatment of periodontal pockets⁶⁶. It is also as a root canal irrigant or intracanal medicament and as a lubricant during biomechanical preparation⁶⁷. Low levels of the release of the prostaglandins contribute to the anti-inflammatory property.

It has been proved to have multiple therapeutic and antimicrobial properties, especially on Enterococcus faecalis⁶³.

It has been proven in several studies that Aloe Vera shows considerable antimicrobial activity against various species such as Streptococcus pyogen, Enterococcus faecalis, Candida albicans and staphylococcus aureus⁶⁸.

Anti-inflammatory property is due to the inhibition of prostaglandin E2 production from arachidonic acid. A compound called C-glucosyl chromone was isolated from gel extracts, which is responsible for anti-inflammatory activity⁶⁹. Carboxypeptidase in aloe vera had good anti-prostaglandin synthesis properties and compounds inhibiting oxidation of arachidonic acid, which might decrease inflammation.

Analgesic property is due to the inhibitory action of aloe vera on the arachidonic acid pathway via cyclooxygenase, also aid in reducing the inflammation⁷⁰.

Presence of carboxypeptidase in Aloe vera inactivates bradykinin by about 67% and relieves pain⁷¹.

Aloe vera has the potential to reduce the effects of the inflammatory cascade and promote bone neoformation⁷².

Wound healing property of Aloe Vera is used is due to the presence of Glucomannan, amannose rich polysaccharide and gibberellin (growth hormone) which interacts with insulin like growth factors and cause stimulation of the fibroblasts in the pulp tissue thereby increasing the collagen synthesis⁷³.

Magnesium lactate present in aloe vera gel inhibits histidine decarboxylase, thereby preventing the formation of histamine from the mast cells thereby producing anti-inflammatory activity.

Also, in 1989 a study done by Davis et al found that wound healing was superior when aloe vera gel was used and stated that it is due to increased blood supply; increased oxygenation, which stimulates the fibroblast activity leading to collagen proliferation⁷⁴.

Yagi et al., 1987 stated that the presence of glycoprotein along with cellular proliferation improves healing. Vitamin C is involved in collagen synthesis, which causes dilatation of blood vessels thereby increasing the oxygen concentration at the site of the wound resulting in healing⁷⁵.

Thompson et al., 1991 reported that the topical application of the Aloe-Vera gel stimulated fibroblast activity and collagen proliferation⁷⁶.

In an animal model, Gala-Garcia et al., 2008 evaluated the effect of Aloe vera on rat pulp tissue and found to have acceptable biocompatibility and can also lead to tertiary dentinal bridge formation. This is because of the presence of glycoprotein and polysaccharides which produces angiogenesis and helps in healing⁷⁷.

ALLIUM SATIVUM:

Allium Sativum is the most commonly used medicinal plants due to its antibacterial activity which depends on allicin produced by the enzyme alliinase (a cysteine sulfoxide lyase)⁷⁸.

Allium Sativum (Garlic) inhibits various Gram-positive and Gram-negative bacteria and multidrug resistant strains of Streptococcus mutans isolated from human carious teeth⁷⁹. The antibacterial activity of A. sativum is due to the allicin which is produced through the enzymatic activity of allinase.

The antibacterial effect of A. sativum oil on the previously mentioned microbes was greater than that of FC. It has also antiviral and antifungal properties⁸⁰.

In a clinical study comparing Allium Sativum (AS) and FC pulpotomy, found that the success rates of A. sativum oil was 90% compared to the 85% with formocresol. The clinical and radiographic outcome were assessed after 6 months and found that they were no statistical significant difference between two groups. A. sativum oil showed a good healing potential of the remaining radicular pulp tissue⁸⁰.

ANKAFERD BLOOD STOPPER:

Ankaferd Blood Stopper (ABS, Ankaferd Health Products Ltd, Turkey) is a unique hemostatic agent used in turkey, approved by the Turkish Ministry of Health in the management of external haemorrhage and for dental extractions. is made of five plants namely Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum and Urticadioica and has widely been used as haemostatic agent due to its rapid formation of a protein network and erythrocyte aggregation⁸¹. It has some effect on the endothelium, blood cells, angiogenesis, cellular proliferation, vasculardynamics and cell mediators without affecting coagulation pathway. Cagdas cinar et al, (2012) found that although Ankaferd Blood Stopper is a potent antibacterial agent, the zones of inhibition of bacteria were found to be smaller than FS and Chlorhexidine.

A study in 2012 evaluated the clinical and radiographic success of FC an Ankaferd Blood Stopper and found that total success rates in the formocresol group was 89.3% compared to the experimental group with Ankaferd Blood Stopper which was 85.7% but there was no statistical significant difference between the groups at 3, 6 and 12 months follow up⁸².

The study conducted in 2011 reported that the total success rate of calcium hydroxide with Ankaferd blood stopper after 12 months was 95% and calcium hydroxide group showed 90% success. There was no statistically significant difference between the groups. Internal resorption was the common failure in both the groups⁸³.

In 2014, another clinical trial was conducted which evaluated the clinical and radiographic success rates of Ankaferd Blood Stopper (ABS) and ferric sulphate. At 12 month follow up the clinical and radiographic success rates of ferric sulphate was approximately 90.9% and 87.8% respectively and for ABS group it was 84.8%. Teeth treated with ABS showed a slightly lower success rate than those treated with ferric sulphate, but not statistically significant⁸⁴. It is not only an effective hemostatic agent, but also confers anti-infective, antineoplastic, and healing modulator properties.

PROPOLIS:

It is a resinous beehive product. It has antibacterial, antioxidant and anti- inflammatory action. Its effect is by the presence of flavanoids such as pinobanksin, quercetin, naringen, galangine, chrysin and aromatic acid such as caffeic acid⁸⁵.

Propolis, has gained popularity in dentistry as an intracanal medicament, as a cariostatic agent, for storage of avulsed teeth and also as a root canal irrigant due to its known anti bacterial, anti-inflammatory and immunomodulating properties⁸⁶. The antibacterial activity of propolis is due to flavonoids and aromaticacids and esters present in resin.

The ethanolic extract of propolis showed high antibacterial against gram positive microorganisms and least activity against gram negative species⁸⁷.

Park YK, 2002 in his study reported that Propolis helps in collagen synthesis and assists in wound healing⁸⁸. It was reported that propolis showed least inflammation and greater fibrous tissue formation and maintained pulp vitality also after 42 days complete calcific bridge was formed. Hence, propolis has a potential to be used as pulpotomy agents⁸⁹.

A pulpotomy clinical trial was conducted in 2015 comparing Mineral Trioxide Aggregate, biodentine and propolis found that clinical and radiographic success were more favourable for MTA and biodentine compared to propolis at 9 months follow up⁹⁰.

Elaegnus Angustifolia:

Elaegnus Angustifolia fruit also known as a Russian olive. It is a potent antinflammatory agent due to its antioxidant properties of flavenoids and terpenoids. It has also analgesic, antipyretic and coagulation properties. Animal study by Talaei Khozani et al., 2011 on embryo of mice found that there was no toxicity associated with this fruit⁹¹.

(Hamidreza Poureslami et al, 2015) in their study assessed the degree of pain during 10 days after the treatment in Elaegnus Angustifolia group and formocresol used as a pulpotomy medicament and found that the pain was decreased significantly in both the groups but the decrease in the formocresol group was more than Elaegnus Angustifolia group.

4.5 Clinical Trials in Primary Teeth using Aloe vera as a pulpotomy medicament:

In a clinical trial which evaluated aloe vera gel as a pulpotomy medicament for a period of 2 months. They reported 100% clinical success rate in primary molars treated with Aloe vera. There was absence of pain, mobility or abscess. Histological analysis showed the presence of vital radicular pulp in the teeth treated with aloe vera⁹².

In 2017, study was done comparing ale vera plant extract and Mineral Trioxide Aggregate. They reported that the overall success rates at the end of 12-month follow-up period were 6.9% for aloe vera group and 71.4% for MTA group and the difference was statistically significant. MTA pulpotomy was found to be superior when compared to fresh A. barbadensis plant extract pulpotomy in primary molars⁹³. Its use as a pulpotomy medicament compared with the gold standard medicament such as formocresol, which has excellent clinical success rate in primary teeth has not been documented in the literature.

CONCLUSION:

Proper clinical investigations, diagnosis and selection of materials is the foremost important tool for the success of pulpotomy technique. Many pulpotomy medicaments have been researched and used which has its own advantages and disadvantages. Recently, bio regenerative materials are widely used due to excellent biocompatibility and rapidity in formation of reparative dentin. Recently, there is a paradigm shift towards using herbal medicine in the field of dentistry, especially endodontics. Greater number of long term clinical trials are necessary to validate and substantiate its efficacy and prove it as an ideal pulpotomy medicament in primary teeth.

REFERENCES:

1 Sweet CA: Treatment of vital primary teeth with pulpal in- volvement. Therapeutic pulpotomy. J Colorado D A 33:10-14, 1955.

2 Shell JE. Formocresol pulp therapy. Dent Stud. 1972 Apr; 50(7):43.

3 Vij R, Coll JA, Shelton P, Farooq NS. Caries control and other variables associated with success of primary molar vital pulp therapy. Pediatr Dent. 2004 Jun;26(3): 214–20.

4 Beaver HA, Kopel HM, Sabes WR. The effect of zinc oxide-eugenol cement on a formocresolized pulp. J Dent Child. 1966 Nov; 33(6):381–96.

5 Ranly DM, Lazzari EP. The formocresol pulpotomy--the past, the present, and the future. J Pedod. 1978;2(2):115–27.

6 Fuks AB. Current concepts in vital primary pulp therapy. Eur J Paediatr Dent. 2002 Sep; 3(3):115–20.

7 Duggal MS, Gautam SK, Nichol R, Robertson AJ. Paediatric dentistry in the new millennium: 4. Cost-effective restorative techniques for primary molars. Dent Update. 2003 Oct; 30(8):410–5.

8 Massler, M., and Mansukhani, N. Effects of Formol-cresol on the Dental Pulp, J. Dent. Child, 26:277-97,1959.

9 Florey L. General pathology. 4 ^th ed. Philadelphia: WB Saunders Co; 1970.Vol. 37, p. 434.

10 Rolling, I., Hasselgren, G., Tronstad L., 1976. Morphologic and enzyme histochemical observations on the pulp of human primary molars 3 to 5 years after formocresol treatment. Oral. Surg. Oral. Med. Oral. Pathol. 42, 518–528.

11 Berger, J., 1965. Pulp tissue reaction from formocresol and zinc oxide and eugenol. J. Dent. Child. 32, 13.

12 Seow, W.K., Thong, Y.H., 1991. Development of a microcolumn radiometric assay for bacterial adherence. Journal of Microbiological Methods 13, 39–48.

13 Wright, F.A., Widmer, R.P.,1979. Pulpal therapy in primary molar teeth: A retrospective study. J. Pedod. 3, 195-206.

14 Ranly, D.M., Pope, H.O., 1979. An in vitro comparison of the release of 3H-formaldehyde and 14C-p-cresol from zinc oxide eugenol cement. Pharmacol. Ther. Dent. 4, 53–57.

15 Milnes, A.R., 2008. Is formocresol obsolete? A fresh look at the evidence concerning safety issues. Pediatr Dent 30, 237–246.

16 Morawa, A.P., Straffon, L.H., Han, S.S., Corpron, R.E., 1975. Clinical evaluation of pulpotomies using dilute formocresol. ASDC. J. Dent. Child. 42, 360–363.

17 Loos, P.J., Straffon, L.H., Han, S.S., 1973. Biological effects of formocresol. ASDC. J. Dent. Child. 40, 193–197.

18 Rølling, I., Poulsen, S., 1978. Formocresol pulpotomy of primary teeth and occurrence of enamel defects on the permanent successors. Acta. Odontol. Scand. 36, 243–247.

19 Pashley, E.L., Myers, D.R., Pashley, D.H., Whitford, G.M., 1980. Systemic distribution of 14C-formaldehyde from formocresol-treated pulpotomy sites. J. Dent. Res. 59, 602–608.

20 Ranly, D.M., 1984. Formocresol toxicity. Current knowledge. Acta Odontol Pediatr 5, 93–98.

21 Casas, M. J., Kenny, D. J., 2005. Do we still need formocresol in pediatric dentistry? J. Can. Dent. Assoc. 71, 749–751.

22 Ranly, D.M., 1985. Assessment of the systemic distribution and toxicity of formaldehyde following pulpotomy treatment: Part one. ASDC. J. Dent. Child. 52, 431–434.

23 Block, R.M., Lewis, R.D., Sheats, J.B., Burke, S.H., 1978. Cell-mediated immune response to dog pulp tissue altered by 6.5% paraformaldehyde via the root canal. J. Endod. 4, 346–352.

24 Kerns, W.D., Pavkov, K.L., Donofrio, D.J., Gralla, E.J., Swenberg, J.A., 1983. Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure. Cancer. Res. 43, 4382–4392.

25 Zhang, W., Yelick, P.C., 2010. Vital pulp therapy-current progress of dental pulp regeneration and revascularization. Int. J. Dent. 28, 1- 9.

26 Eugenia, A.G., Manuela, P.M., Dolores, C.F., Ignacio, V., Juan Jose, S.E., Jose Luis, G.P., 2007. Dentigerous Cyst Associated with a Formocresol Pulpotomized Deciduous Molar. J. Endod. 33, 488-492.

27 Zarzar, P.A., Rosenblatt, A., Takahashi, C.S., Takeuchi, P.L., Costa Júnior, L.A., 2003. Formocresol mutagenicity following primary tooth pulp therapy: an in vivo study. J Dent 31, 479–485.

28 Pruhs, R.J., Olen, G.A., Sharma, P.S., 1977. Relationship between formocresol pulpotomies on primary teeth and enamel defects on their permanent successors. J. Am. Dent. Assoc. 94, 698–700.

29 Dammaschke T. The history of direct pulp capping. J Hist Dent. 2008;56(1):9–23.

30 Siqueira JF, Lopes HP. Mechanisms of antimicrobial activity of calcium hydroxide: a critical review. Int Endod J. 1999 Sep;32(5):361–9.

31 Milosevic A. Calcium hydroxide in restorative dentistry. Journal of Dentistry. 1991 Feb 1;19(1):3–13.

32 Schröder, U., 1985. Effects of calcium hydroxide-containing pulp-capping agents on pulp cell migration, proliferation, and differentiation. J. Dent. Res. 64 Spec No, 541–548.

33 Moretti, A.B.S., Sakai, V.T., Oliveira, T.M., Fornetti, A.P.C., Santos, C.F., Machado, M. a. a. M., Abdo, R.C.C., 2008. The effectiveness of mineral trioxide aggregate, calcium hydroxide and formocresol for pulpotomies in primary teeth. Int. Endod. J. 41, 547–555.

34 Markovic, D., Zivojinovic, V., Vucetic, M., 2005. Evaluation of three pulpotomy medicaments in primary teeth. Eur. J. Paediatr. Dent. 6, 133–138.

35 Fei, A.L., Udin, R.D., Johnson, R., 1991. A clinical study of ferric sulfate as a pulpotomy agent in primary teeth. Pediatr. Dent. 13, 327–332.

36 Ranly, D.M., 1994. Pulpotomy therapy in primary teeth: new modalities for old rationales. Pediatr. Dent. 16, 403–409.

37 Ibricevic, H., Al-Jame, Q., 2003. Ferric sulphate and formocresol in pulpotomy of primary molars: long term follow-up study. Eur. J. Paediatr. Dent. 4, 28–32.

38 Sirohi, K., Marwaha, M., Gupta, A., Bansal, K., Srivastava, A., 2017. Comparison of Clinical and Radiographic Success Rates of Pulpotomy in Primary Molars using Ferric Sulfate and Bioactive Tricalcium Silicate Cement: An in vivo Study. Int. J. Clin. Pediatr.Dent. 10, 147–151.

39 Garcia-Godoy F. Evaluation of an iodoform paste in root canal therapy for infected primary teeth. ASDC J Dent Child. 1987; 54:30–4.

40 Tsai TP, Su HL, Tseng LH. Glutaraldehyde preparations and pulpotomy in primary molars. Oral Surg Oral Med Oral Pathol. 1993 Sep; 76(3):346–50.

41 Havale R, Anegundi RT, Indushekar K, Sudha P. Clinical and radiographic evaluation of pulpotomies in primary molars with formocresol, glutaraldehyde and ferric sulphate. Oral Health Dent Manag. 2013 Mar;12(1):24–31.

42 Magnusson, B., 1970. Attempts to predict prognosis of pulpotomy in primary molars. Scand. J. Dent. Res. 78, 232-240.

43 Gonzalez-Lara A, Ruiz-Rodriguez MS, Pierdant-Perez M, Garrocho-Rangel JA, Pozos-Guillen AJ. Zinc Oxide-Eugenol Pulpotomy in Primary Teeth: A 24-Month Follow-up. J Clin Pediatr Dent. 2016;40(2):107–12.

44 Udin RD. The formocresol pulpotomy revisited: looking at alternatives. J Calif Dent Assoc. 1991 Sep;19(9):27–34.

45 Sheller B, Morton TH. Electrosurgical pulpotomy: a pilot study in humans. J Endod. 1987 Feb;13(2):69–76.

46 Mack RB, Dean JA. Electrosurgical pulpotomy: a retrospective human study. ASDC J Dent Child. 1993 Apr;60(2):107–14.

47 Shulman ER, McIver FT, Burkes EJ. Comparison of electrosurgery and formocresol as pulpotomy techniques in monkey primary teeth. Pediatr Dent. 1987 Sep;9(3):189–94.

48 Mortazavi, S.M.J., Mortazavi, G., Paknahad, M., 2016. Positive correlation of serum HDL cholesterol with blood mercury concentration in metabolic syndrome Korean men (analysis of KNANES 2008-2010, 2013). J. Endocrinol. Invest. 39, 1363–1364.

49 The Obsolescence of Formocresol | Earth & Life Sciences | Biology [Internet]. Scribd. [cited 2017 Dec 8]. Available from: https://www.scribd.com/document/299926945/The-Obsolescence-of-Formocresol

50 Pinar Erdem A, Guven Y, Balli B, Ilhan B, Sepet E, Ulukapi I, et al. Success rates of mineral trioxide aggregate, ferric sulfate, and formocresol pulpotomies: A 24-month study. Pediatric dentistry. 2011 Apr 1; 33:165–70.

51 Shoji S, Nakamura M, Horiuchi H. Histopathological changes in dental pulps irradiated by CO₂laser: a preliminary report on laser pulpotomy. J Endod. 1985; 11:773–80.

52 Saltzman B., Sigal M., Clokie C., Rukavina J., Titley K., and Kulkarni G.V. (2005). Assesment of a novel alternative to conventional formocresol-zinc oxide eugenol pulpotomy for the treatment of pulpally involved human primary teeth: diode laser-mineral trioxide aggragate pulpotomy. Int. J. Pediatr. Dent. 15, 437–447

53 Liu J. Effects of Nd:YAG laser pulpotomy on human primary molars. J Endod. 2006 May;32(5):404–7.

54 Torabinejad M, Parirokh M. Mineral trioxide aggregate: a comprehensive literature review--part II: leakage and biocompatibility investigations. J Endod. 2010 Feb;36(2):190–202.

55 Sarris S, Tahmassebi JF, Duggal MS, Cross IA. A clinical evaluation of mineral trioxide aggregate for root-end closure of non-vital immature permanent incisors in children-a pilot study. Dent Traumatol. 2008 Feb;24(1):79–85.

56 Parisay I, Ghoddusi J, Forghani M. A Review on Vital Pulp Therapy in Primary Teeth. Iran Endod J. 2015;10(1):6–15.

57 Khan J, El-Housseiny A, Alamoudi N. Mineral Trioxide Aggregate Use in Pediatric Dentistry: A Literature Review. Journal of Oral Hygiene & Health [Internet]. 2016 Nov 21 [cited 2017 Dec 8]; 4(5). Available from: https://www.omicsonline.org/open-access/mineral-trioxide-aggregate-use-in-pediatric-dentistry-a-literature-review-2332-0702-1000209.php?aid=83789

58 Farsi N, Alamoudi N, Balto K, Mushayt A. Success of mineral trioxide aggregate in pulpotomized primary molars. J Clin Pediatr Dent. 2005; 29(4):307–11.

59 Erdem AP, Guven Y, Balli B, Ilhan B, Sepet E, Ulukapi I, et al. Success rates of mineral trioxide aggregate, ferric sulfate, and formocresol pulpotomies: a 24-month study. Pediatr Dent. 2011 Apr; 33(2):165–70.

60 Malkondu Ö, Kazandağ MK, Kazazoğlu E. A Review on Biodentine, a Contemporary Dentine Replacement and Repair Material [Internet]. BioMed Research International. 2014 [cited 2017 Dec 8].

61 Bachoo IK, Seymour D, Brunton P (2013) A biocompatible and bioactive replacement for dentine: is this a reality? The properties and uses of a novel calcium-based cement. Br Dent J 214: 1-7.

62 Sirohi, K., Marwaha, M., Gupta, A., Bansal, K., Srivastava, A., 2017. Comparison of Clinical and Radiographic Success Rates of Pulpotomy in Primary Molars using Ferric Sulfate and Bioactive Tricalcium Silicate Cement: An in vivo Study. Int. J. Clin. Pediatr.Dent. 10, 147–151.

63 Hamman, J.H., 2008. Composition and applications of Aloe vera leaf gel. Molecules. 13, 1599–1616.

64 Yamaguchi, I., Mega, N., Sanada, H., 1993. Components of the gel of Aloe vera (L.).burm. f. Biosci. Biotechnol. Biochem. 57, 1350–1352.

65 Mohan, R., Gundappa, M., 2013. Aloe vera in dentistry – The herbal panacea. Indian. J. Dent. Sci. Res. 29, 15–20.

66 Tello CG, Ford P, Iacopino AM. In vitro evaluation of complex carbohydrate denture adhesive formulations. Quintessence Int. 1998;29:585–93.

67 Sudworth R. Philadelphia: Positive Health Publications Ltd; 2002. The use of Aloe Vera in Dentistry.

68 Jittapiromsak N, Sahawat D, Banlunara W, Sangvanich P, Thunyakitpisal P. Acemannan, an extracted product from Aloe vera, stimulates dental pulp cell proliferation, differentiation, mineralization, and dentin formation. Tissue Eng Part A. 2010 Jun;16(6):1997–2006.

69 Hutter JA, Salman M, Stavinoha WB, Satsangi N, Williams RF, Streeper RT, et al. Antiinflammatory C-glucosyl chromone from Aloe barbadensis. J Nat Prod. 1996 May;59(5):541–3.

70 Vázquez B, Avila G, Segura D, Escalante B. Antiinflammatory activity of extracts from Aloe vera gel. J Ethnopharmacol. 1996 Dec;55(1):69–75.

71 Bunyapraphatsara N, Jirakulchaiwong S, Thirawarapan S, Manonukul J. The efficacy of Aloe vera cream in the treatment of first, second and third degree burns in mice. Phytomedicine. 1996 Jan 1;2(3):247–51.

72 Fé JLM, Coelho C de A, Damascena GM, Soares IMV, Alves FR, Santos ÍMSP, et al. Aloe vera as vehicle to mineral trioxide aggregate: study in bone repair. Revista de Odontologia da UNESP. 2014 Oct; 43(5):299–304.

73 Renu, et al., 2011. Aloevera and its uses in dentistry. Indian. J. dent. Adv. 3, 656-658.

74 Davis, R.H., Donato, J.J., Hartman, G.M., Haas, R.C., 1994. Anti-inflammatory and wound healing activity of a growth substance in Aloe vera. J. Am. Podiatr. Med. Assoc 84, 77–81.

75 Thompson, J.E., 1991. Topical use of aloe vera derived allantoin gel in otolaryngology. Ear Nose Throat J 70, 56.

76 Gala-Garcia, A., Teixiera, K.I.R., Mendes, L.L., Sobrinho, A.P.R., Santos, V.R., Cortes, M.E., 2008. Effect of Aloe vera on rat pulp tissue. Pharmaceutical. Biology. 46, 302-308.

77 Mohammad SG, Baroudi K. Assessment of the potential of Allium sativum oil as a new medicament for non-vital pulpotomy of primary teeth. J Int Soc Prev Community Dent. 2015;5(4):314–20.

78 Martin KW, Ernst E. Herbal medicines for treatment of bacterial infections: A review of controlled clinical trials. J Antimicrob Chemother. 2003;51(2):241–6.

79 Ankri S, Mirelman D. Antimicrobial properties of allicin from garlic. Microbes Infect. 1999; 1:125–9.

80 Mohammad SG, Raheel SA, Baroudi K. Clinical and Radiographic Evaluation of Allium sativum Oil as a New Medicament for Vital Pulp Treatment of Primary Teeth. J Int Oral Health. 2014; 6(6):32–6.

81 Goker H, Haznedaroglu IC, Ercetin S, Kirazli S, Akman U, Ozturk Y, et al. Haemostatic actions of the folkloric medicinal plant extract Ankaferd blood stopper. J Int Med Res 2008;36:163-70.

82 Yaman E, Görken F, Pinar Erdem A, Sepet E, Aytepe Z. Effects of folk medicinal plant extract Ankaferd Blood Stopper(®) in vital primary molar pulpotomy. Eur Arch Paediatr Dent. 2012 Aug; 13(4):197–202.

83 Mihmanli A, Ulker Z, Alpsoy L, Ezirganli S. Evaluation of cytotoxicity of a new hemostatic agent Ankaferd Blood Stopper® using different assays. Hum Exp Toxicol. 2012 Aug;31(8):780–7.

84 Cantekin K, Gümüş H. Success Rates of Ankaferd Blood Stopper and Ferric Sulfate as Pulpotomy Agents in Primary Molars. Int Sch Res Notices. 2014; 2014:819605.

85 Shingare, P., Chaugule, V., 2011. Comparative evaluation of antimicrobial activity of miswak, propolis, sodium hypochlorite and saline as root canal irrigants by microbial culturing and quantification in chronically exposed primary teeth. Germs. 1, 12– 16.

86 Banskota, A.H., Tezuka, Y., Kadota, S., 2001. Recent progress in pharmacological research of propolis. Phytother. Res 15, 561–571.

87 Pujar, M., Makandar, S., 2011. Herbal usage in endodontics-A review. Int. J. Contemp. Dent. 2, 34–37.

88 Park, Y.K., Alencar, S.M., Aguiar, C.L., 2002. Botanical origin and chemical composition of Brazilian propolis. J. Agric. Food Chem. 50, 2502–2506.

89 Ozório, J.E.V., Carvalho, L.F. de O.E.S., de Oliveira, D.A., de Sousa-Neto, M.D., Perez, D.E. da C., 2012. Standardized propolis extract and calcium hydroxide as pulpotomy agents in primary pig teeth. J. Dent. Child (Chic). 79, 53–58.

90 Kusum B, Rakesh K, Richa K. Clinical and radiographical evaluation of mineral trioxide aggregate, biodentine and propolis as pulpotomy medicaments in primary teeth. Restor Dent Endod. 2015 Nov; 40(4):276–85.

91 Talaei-Khozani T, Vojdani Z, Dehghani F, Heidari E, Kharazinejad E, Panjehshahin MR. Toxic effects of Elaeagnus angustifolia fruit extract on chondrogenesis and osteogenesis in mouse limb buds. Tokai J Exp Clin Med. 2011 Sep 20;36(3):63–70.

92 Gupta, N., Bhat, M., Devi, P., Girish, null, 2010. Aloe-Vera: A Nature’s Gift to Children. Int J Clin Pediatr Dent 3, 87–92.

93 Kalra, M., Garg, N., Rallan, M., Pathivada, L., Yeluri, R., 2017. Comparative Evaluation of Fresh Aloe barbadensis Plant Extract and Mineral Trioxide Aggregate as Pulpotomy Agents in Primary Molars: A 12-month Follow-up Study. Contemp. Clin. Dent. 8, 106–111.

Received on 08.12.2017 Modified on 12.01.2018

Research J. Pharm. and Tech 2018; 11(6): 2647-2655.

DOI: 10.5958/0974-360X.2018.00491.2