DOI: 10.7860/JCDR/2014/7719.3980 Review Article Recent Advances in Pulp Capping Materials: An Overview Dentistry Section

Asma Qureshi1, Soujanya E.2, Nandakumar3, Pratapkumar4, Sambashivarao5 ­ ABSTRACT Emphasis has shifted from the “doomed” organ concept of an exposed pulp to one of hope and recovery. The era of vital-pulp therapy has been greatly enhanced with the introduction of various pulp capping materials. The aim of this article is to summarize and discuss about the various and newer pulp capping materials used for protection of the dentin-pulp complex.

Keywords: Biocompatible,Dentin bridge, Pulp capping, Pulp capping agent, Reparative dentin

INTRODUCTION Keflin (cephalothin sodium) along with calcium hydroxide was used Historically, the first pulp capping procedure was performed in for pulp capping with the thought of reducing or preventing pulp 1756, by the Phillip pfaff, who packed a small piece of gold over an inflammation. exposed vital pulp to promote healing. However, the success of the Gardner et al., found that vancomycin, in combination with calcium pulp capping procedure greatly depends upon the circumstances hydroxide was somewhat more effective than calcium hydroxide under which it is performed and the prognosis depends upon the used alone and stimulated a more regular reparative dentin bridge. age, type, site and size of pulp exposure. In addition to this the pulp Watts and Paterson cautioned that anti-inflammatory compounds capping material should have the following ideal properties like should not be used in patients at risk from bacteremia [5]. • Stimulate reparative dentin formation • Maintain pulpal vitality Polycarboxylate Cement McWalter G et al., found that it lacks an antibacterial effect and • Release fluoride to prevent secondary caries calcific bridge formation [6]. • Bactericidal or bacteriostatic • Adhere to dentin Inert Materials • Adhere to restorative material Bhaskar SH et al., and Heys DR et al., investigated isobutyl cyanoacrylate and tricalcium phosphate ceramic as direct pulp • Resist forces during restoration placement and during the capping materials. Although pulpal response in the form of reduced of restoration. inflammation and unpredictable dentin bridging were found, but • Sterile none of these materials have been promoted to the dental profession • Radiopaque as a viable technique [5]. • Provide bacterial seal [1]. Collagen Calcium Hyroxide Dick et al., reported that collagen fibers are less irritating than Ca (OH)2 and promotes mineralisation but does not help in thick dentin Calcium hydroxide (Ca (OH) 2) was introduced to the dental profession in 1921 by Hermann and has been considered the “gold standard” bridge formation [7]. of direct pulp capping materials for several decades, against which new materials should be, tested [2-4]. Bonding Agents According to Miyakoshi et al., 4-META-MMA-TBB adhesives and Zinc Oxide Eugenol Cement hybridizing dentin bonding agents provide superior adhesion to Tronstad and Mjör stated that Zinc oxide eugenol cement (ZOE) peripheral hard tissues and effective seal against micro leakage. But is more beneficial for inflamed and exposed pulp. However in they have poor outcome due to its cytotoxic effect and absence of the literature and Zander, Hembree and Andrews, Watts, calcific bridge formation [5]. Holland et al., found that ZOE, in direct contact with the pulp tissue, produced chronic inflammation, lack of calcific barrier, and end Calcium Phosphate result is necrosis [5]. Calcium phosphate cement was suggested as viable alternative because of its good biocompatibility, superior compressive strength Corticosteroids and Antibiotics and its transformation into hydroxyapatite over time. Yoshimine et Corticosteroids like hydrocortisone, Cleocin, cortisone, Ledermix al., demonstrated that in contrast to calcium hydroxide, tetracalcium (calcium hydroxide plus prednisolone), penicillin, neomycin and phosphate cement induced bridge formation with no superficial

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tissue necrosis and significant absence of pulp inflammation [8]. Other Growth Factors Hu et al., evaluated the various growth factors like epidermal growth Hydroxyapatite factor, basic fibroblast growth factor, insulin-like growth factor It is the most thermo dynamically stable of the synthetic calcium II, platelet-derived growth factor-BB, TGF-b 1in rat molars and phosphate ceramics. It has good biocompatibility with neutral pH concluded that only TGF-b 1-enhances reparative dentin formation -7.0. It can be used as scaffolding for the newly formed mineralized [20]. tissue [9]. Bonesialoprotein According to Goldberg M et al., Bone sialoprotein (BSP) was the Melcer et al., suggested between the years 1985 and 1987 that most efficient bioactive molecule, which induced homogeneous and well mineralized reparative dentin. Both BSP and BMP-7 the carbon dioxide (CO2) (1W) used for direct pulp capping [10-12]. were superior to calcium hydroxide in their mineralization inducing properties [21]. Y. Yasuda et al., did a study to examine the effect of CO2 laser irradiation on mineralization in dental pulp cells in rats and the

results suggested that CO2 laser irradiation stimulated mineralization Biodentin in dental pulp cells [13]. Biodentine is new bioactive cement with dentin like mechanical Nd: YAG laser emits an infrared beam at a wavelength of 1064nm properties and can be used as dentin substitute. It has a positive ­ can be of therapeutic benefit for direct pulp capping and pulpotomy effect on vital pulp cells and stimulates tertiary dentin formation [22]. in clinical practice [14]. Enzymes Glass Ionomer/Resin Modified Glass Ionomer Heme-Oxygenase-1 Glass ionomer also provides an excellent bacterial seal and good Heme oxygenase-1(HO) is the rate limiting enzyme in heme biocompatibility when used in close approximation but not in direct catabolism. Odontoblasts and oxidatively stressed dental pulp cells contact with the pulp. express HO-1, indicates that the pulp might respond to oxidative Keywords: Biocompatible,Dentin bridge, Pulp capping, Pulp capping agent, Reparative dentin RMGIC as direct pulp capping agent exhibited chronic inflammation stress at the molecular level. and lack of dentin bridge formation; whereas the calcium hydroxide HO-1 induction protects against hypoxic stress and nitric oxide- control groups showed significantly better pulpal healing [15]. mediated cytotoxicity. It has been reported that HO-1 might play a cytoprotective role against pro inflammatory cytokines and nitric Mineral Trioxide Aggregate oxide in human pulp cells. In addition, bismuth oxide containing Mineral Trioxide Aggregate (MTA) was introduced by Torabinejad in Portland cement (BPC) induced HO-1 expression in dental pulp early 1900s. Several studies reported that MTA induced less pulpal cells plays a protective role against the cytotoxic effects of BPC [23]. inflammation and more predictable hard tissue barrier formation in comparison to hard setting calcium hydroxide [16]. Simvastatin It is a 3-hydroxy-3-methylglutaryl coenzyme, a reductase inhibitor MTYA1-Ca and first line drug for hyperlipidemia. Statin improves the osteoblast Atsuko Niinuma developed resinous direct pulp capping agent function via the BMP-2 pathway and suppresses osteoclast function, containing calcium hydroxide. The powder composed of 89.0% resulting in enhanced bone formation. Therefore, statin might microfiller, 10.0% calcium hydroxide and 1.0% benzoyl peroxide and improve the function of odontoblasts, thus leading to improved was mixed with liquid (67.5% triethyleneglycol dimethacrylate, 30.0% dentin formation. glyceryl methacrylate, 1.0% o-methacryloyl tyrosine amide, 1.0% Statin is known to induce angiogenesis and increase neuronal cells, dimethylaminoethylmethacrylate and 0.5% camphorquinone). indicating the possible effectiveness of statin in pulp regeneration MTYA1-Ca developed dentine bridge formation without formation of along with dentin regeneration. It has an anti-inflammatory effect a necrotic layer, revealed to have good physical properties, and was in various tissues, so it is considered as an ideal active ingredient not inferior to Dycal histopathologically. Therefore, it is suggested in pulp capping material to accelerate reparative dentin formation that the newly developed material, MTYA1-Ca promises to be a [24]. good direct pulp capping material [17]. Stem Cells Growth Factors Dental pulp stem cells (DPSCs) and Stem cells from Human Growth factors regulate growth and development and induce wound Exfoliated Deciduous Teeth (SHED) have been identified as a novel healing and tissue regeneration. population of stem cells that have the capacity of self-renewel and Bone Morphogenic (BMP) multi lineage differentiation. Bone Morphogenic Protein (BMP) belongs to super family trans­ Sayaka Nakamura et al., used mesenchymal stem cells for clinical forming growth factor beta (TGF-b). TGF b is a potent modulator of application in tissue engineering and regenerative . In tissue repair in different situations. BMP-2, 4, and 7 plays a role in this study, they compared the proliferation and stem cell marker the differentiation of adult pulp cells into odontoblasts during pulpal of SHED, DSPCs and Bone Marrow Derived Mesenchymal Stem healing. Cells (BMMSCs). In addition, expression profile of DSPCs and Lianjia et al., found that BMPs are responsible for dentinogenesis,­ SHED were analyzed by using DNA . They concluded inducing non differentiated mesenchymal cells from the pulp to form that SHED has got significantly higher proliferation rate than that of odontoblast-like cells, obtaining osteodentin and tubular dentin DSPCs and BMMSCs and this could be a desirable option as a cell deposition, when used as direct protectors [18]. source for therapeutic applications [25]. Recombinant Insulin Like Growth Factor-I Lovaschall et al., evaluated recombinant insulin like growth factor-I Propolis (Russian penicillin) (rhIGF-I) in rat molars and concluded that dentin bridge formation It contains flavonoids, phenolics, iron, zinc and other various was equal to dycal after 28 days [19]. aromatic compounds [26].

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A Parolia et al., compared propolis, MTA and Dycal histologically in protective base/liner under composites, amalgams, cements, and human dental pulp and concluded that Propolis and MTA showed other base materials. TheraCal LC performs as an insulator/barrier similar bridge formation when compared to Dycal [27]\. and protectant of the dental pulpal complex. The proprietary formulation of TheraCal LC consists of tricalcium Novel Endodontic Cement silicate particles in a hydrophilic monomer that provides significant Novel endodontic cement (NEC) consists of calcium oxide, calcium calcium release making it a uniquely stable and durable material phosphate, calcium carbonate, calcium silicate, calcium sulfate, as a liner or base. Calcium release stimulates hydroxy apatite and and calcium chloride. secondary dentin bridge formation. TheraCal LC may be placed Mohammad Hassan Zarrabi evaluated MTA and NEC histo­logically directly on pulpal exposures after hemostasis is obtained. It is in human dental pulp and concluded that NEC induced a thicker indicated for any pulpal exposures, including carious exposures, dentinal bridge with less pulp inflammation [28]. mechanical exposures or exposures due to trauma. [Table/Fig-1] shows the physical properties of Theracal LC Emdogain Gandolfi et al., compared chemico physical properties of TheraCal, Emdogain (EMD) is enamel matrix derivative secreted from ProRoot MTA and Dycal and concluded that TheraCal displayed Hertwig’s epithelial root sheath during porcine tooth development. higher calcium releasing ability and lower solubility than either It is an important regulator of enamel mineralization and plays an ProRoot MTA or Dycal. The capability of TheraCal to be cured to a important role during periodontal tissue formation. It stimulates the depth of 1.7 mm may avoid the risk of untimely dissolution. These regeneration of acellular cementum, periodontal ligaments, and properties offer major advantages in direct pulp capping treat­- alveolar bone. ments [36]. [Table/Fig-2] shows the summary of advantages and disadvantages of various pulp capping agents. EMD contains BMP like molecules and BMP expressing cells. BMP like molecules in EMD promote odontoblast differentiation and reparative dentin formation. Recently,it was reported that EMD suppresses the Physical Properties inflammatory cytokine production by immunocytes and contains Shear bond Water solubility Radiopacity Calcium TGF-β like molecules. It might create a favourable environment for strength(Mpa) (µg/mm2) (mm Al) release promoting wound healing in the injured pulp tissues [29]. Theracal LC 4.35 (2.93) 0 2.63 188 (µg/ cm2) Nakamura Y et al., concluded that amount of hard tissue formed Prisma VLC 0.94 (0.92) 110 (17) 0.79 NA in EMD treated teeth was more than twice that of the calcium Dycal hydroxide treated control teeth [30]. [Table/Fig-1]: Shows physical properties of Theracal LC Khalid Al-Hezaimi evaluated Calcium hydroxide, ProRoot White MTA and white Portland cement after Emdogain application on the exposed pulp. MTA produced a better quality reparative hard tissue Pulp capping agent Advantages Disadvantages response with the adjunctive use of Emdogain compared with Ca (OH)2 • Gold standard of direct • Highly soluble in oral calcium hydroxide [31]. (1960’s) pulp capping material fluids • Excellent antibacterial • Subject to dissolution properties over time Odontogenic Ameloblast Associated Protein • Induction of • Extensive dentin mineralization formation obliterating the Odontogenic ameloblast associated protein (ODAM) is expressed • Low cytotoxicity pulp chamber in ameloblasts, odontoblasts, and pulpal cells. ODAM involved in • Lack of adhesion • Degradation after acid ameloblast maturation and enamel mineralization. etching In-Seok Yang et al., stated that rODAM accelerates reactionary • Presence of tunnels in reparative dentin dentin formation close to the pulp exposure area, thereby preserving normal odontoblasts in the remaining pulp [32]. Zinc oxide eugenol • Reduces inflammation • Lack of calcific bridge cement (1960-70’s) formation • Releases eugenol in high Endo Sequence Root Repair Material concentration which is cytotoxic It consists of Calcium silicates, monobasic calcium phosphate, • Demonstrate interfacial zirconium oxide, tantalum oxide, proprietary fillers and thickening leakage agents [33]. Corticosteroids and • Reduces pulp • Should not be used in Hirschman et al., compared Cytotoxicity of MTA-Angelus, Brasseler antibiotics (1970’s) inflammation patients at risk from Endosequence Root Repair Putty (ERRP), Dycal and Ultra-blend • Vanocmycin + Ca(OH)2 bacteremia. Plus (UBP)-(light curable Ca(OH) ) and concluded that ERRP and stimulated a more 2 regular reparative dentin UBP are less cytotoxic [34]. bridge.

Castor Oil Bean Cement Polycarboxylate • Chemically bond to the • Lack of antibacterial cement (1970’s) tooth structure effect The Castor oil bean (COB) consists of 81-96% triglyceride of ricinoleic • Fail to stimulate calcific acid, and is considered a natural polyol containing three hydroxyl bridge formation radicals. COB or RCP (Ricinus Communis Polyurethane) was originally developed as a biomaterial for bone repair and regeneration Inert materials (1970’s) • Reduces pulp • None of these materials (Isobutyl inflammation havebeen promoted to after local bone damage. Due to these positive characteristics, the cyanoacrylate and Tri • Stimulate dentin bridge the dental profession as material is considered to be an excellent candidate for use in pulp calcium phosphate formation a viabletechnique capping [35]. ceramic)

Collagen • Less irritating than • Does not help in thick (1980) • Ca (OH) and promotes dentin bridge formation Theracal 2 mineralisation TheraCal LC is a light cured, resin modified calcium silicate filled liner designed for use in direct and indirect pulp capping, as a

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Bonding agents • Superior adhesion to • Have cytotoxic effect Growthfactors • Formation of • Possibility of unexpected (1995) hard tissues • Absence of calcific (1900-2007) osteodentin and tubular side effects and the 4-META-MMA-TBB • Effective seal against bridge formation Bone Morphogenic dentin production adhesives and microleakage. • In vivo studies have Protein (BMP 2,4,7) • Formation of more • cost can be obstacles for hybridizing dentin demonstrated that Recombinant insulin homogeneous their clinical application bonding agents the application of an like growth factor-I reparative dentin • Fail to stimulate adhesive resin directly Other growth factors • Superior to Ca(OH)2 reparative dentin in onto a site of pulp (1998) in the mineralization inflamed pulp exposure, or to a thin Epidermal growth inducing properties • Half life is less layer of dentin (less factor • Dentin bridge formation • High concentration is than 0.5 mm), causes Fibroblast growth was equal to dycal after required dilatation and congestion factor 28 days • Delivery vechicles used of blood vessels as well Insulin like growth • Only TGF-b1 induced for the molecules show as chronic inflammatory factor II reparative dentin potent effects at the pulpal response Platelet-derived formation pictogram level and growth factor-BB appropriate carriers will TGF-b 1 be required to facilitate their handling in the Calcium phosphate • Helps in bridge • Clinical trials are clinical situation (1900’s) formation with no necessary to evaluate • Appropriate dose superficial tissue this material response is required necrosis to avoid uncontrolled • significant absence obliteration of pulp of pulp inflammation chamber compared to Ca(OH)2 • Possibility of • Good physical immunological problems properties due to repeated implantation of active molecules Hydroxyapatite (1995) • Biocompatible • Mild inflammation with • Other factors does not • Act as scaffold for superficial necrosis of induced reparative dentin the newly formed pulp formation mineralized tissue Bonesialoprotein • Induced homogeneous • Further clinical studies (2000) and well mineralized are needed reparative dentin Lasers (1995-2010) • Formation of secondary • Technique sensitive • Superior to Ca(OH)2 CO2 dentin • Causes thermal damage in the mineralization • sterilization of targeted to pulp in high doses inducing properties Nd: YAG tissue • Technique sensitive • Bactericidal effects • Causes thermal damage Biodentin • Biocompatible • More long-term to pulp in high doses (2000) • Good antimicrobial • clinical studies are activity. needed for a definitive • Stimulate tertiary dentin evaluation of Biodentine formation Glass ionomer/ • Excellent bacterial seal • Causes chronic • Stronger mechanically, • Fluoride release, inflammation less soluble and Resin modified glass coefficient of thermal • Lack of dentin bridge produces tighter seals ionomer expansion and modulus formation compared to Ca(OH)2 (1995) of elasticity similar to • Cytotoxic when in direct • Less setting time, good dentin cell contact handling characteristics • Bond to both enamel • Poor physical properties, than MTA and dentin high solubility and slow ENZYMES • Play a cytoprotective • Further in vitro and in • Good biocompatibility setting rate role against pro vivo studies are required • • RMGIC is more cytotoxic Heme-Oxygenase-1 inflammatory cytokines • In high concentration than conventional GIC, (2008) and nitric oxide in causes pulp tissue so it should not be human pulp cells damage. applied directly to the • Prevent H O induced • Careful evaluation pulp tissue 2 2 cytotoxicity and is required before oxidative stress in clinical application to human dental pulp cells. determine the suitable Mineral trioxide • Good biocompatibility • More expensive Simvastatin (2009) • Anti inflammatory action concentration when aggregate • Less pulpal • Poor handling • Induction of applied indirectly to a (1996-2008) inflammation characterstics angiogenesis cavity or directly to pulp • More predictable hard • Long setting time • Improve the function tissue. tissue barrier formation • Grey MTA causes tooth of odontoblasts, thus in comparison to discoloration leading to improved calcium hydroxide • Two step procedure dentin formation • Antibacterial property • High solubility STEM CELLS • Regeneration of dentin- • Less economic • Radiopacity (2009) pulp complex • Technique sensitive • Releases bioactive Dental pulp stem cells • SHED is superior to dentin matrix (DPSCs) DPSCs Stem cells from human exfoliated deciduous teeth (SHED) MTYA1-Ca • Helps in dentine bridge • Presence of 10%

(1999) formation without Ca(OH)2 interferes Propolis • Antioxidant, • formation of a necrotic with complete curing (2005-2010) antibacterial, antifungal, • Showed mild / layer of material, residual antiviral and anti- moderate inflammation • Shear bond strength is monomers causes inflammatory properties after 2,4 weeks with higher than conventional cytotoxicity • partial dentinal bridge GIC and similar to • Superior bridge formation. RMGIC formation compared • Dentin bridge formation to Dycal, similar results without reduction to MTA of pulp space in • MTYA1-Ca, but there is • Forms dental pulp reduction of pulp space collagen, reduces both is seen in dycal. pulp inflammation and • Better adhesion to degeneration. dentine • • Stimulate reparative dentin formation

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Novel endodontic • Biocompatible • Further assessment is REFERENCES cement • Shorter setting time required for evaluation [1] Cohen BD, Combe EC.Development of new adhesive pulp capping materials. (2010) • Do not cause tooth of pulp response to this Dent Update. 1994; 21(2):57-62. staining material in inflamed pulp. [2] Cox CF, Subay RK, Ostro E, Suzuki S, Suzuki SH. Tunnel defects in dentin bridges: • Good handling Their formation following direct pulp capping. Oper Dent. 1996; 21(1):4-11. characteristics [3] Schröder U. Effects of calcium hydroxide-containing pulp-capping agents on compared to MTA pulp cell migration, proliferation, and differentiation. J Dent Res. 1985; 64:541-8. • Induced a thicker dentinal bridge with less [4] Cox CF, Suzuki S. Re-evaluating pulp protection: calcium hydroxide liners vs. pulp inflammation than cohesive hybridization. J Am Dent Assoc. 1994; 125(7):823-31. MTA [5] Ingle, Bakland.Textbook of Endodontics-Fifth Edition.pg.no.861-902. 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Wound healing process of injured pulp ability and lower tissues with emdogain gel. J Endod. 2008; 34(1): 26-30. solubility than either [30] Nakamura Y, Hammarström L, Lundberg E, Ekdahl H, Matsumoto K, Gestrelius S ProRoot MTA or Dycal et al.,.Enamel matrix derivative promotes reparative processes in the dental pulp. Adv Dent Res. 2001; 15: 105-7. [Table/Fig-2]: Shows the summary of advantages and disadvantages of various [31] Al-Hezaimi K, Al-Tayar BA, Bajuaifer YS, Salameh Z, Al-Fouzan K, Tay FR. A hybrid pulp capping agents approach to direct pulp capping by using emdogain with a capping material. J Endod. 2011; 37(5): 667-72. [32] Yang IS, Lee DS, Park JT, Kim HJ, Son HH, Park JC. Tertiary dentin formation CONCLUSION after direct pulp capping with odontogenic ameloblast-associated protein in rat Clarity on the of caries, comprehension of technological teeth. 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three current direct pulp-capping agents with a new bioceramic root repair putty.J [36] Gandolfi G M , Siboni F, Prati C. Chemical-physical properties of TheraCal, a Endod. 2012; 38(3): 385-8. novel light-curable MTA-like material for pulp capping. Int Endod J. 2012; 45(6): [35] Camargo SE, Camargo CH, Hiller KA, Rode SM, Schweikl H, Schmalz G. 571-9. Cytotoxicity and genotoxicity of pulp capping materials in two cell lines. Int Endod J. 2009; 42(3): 227-37.

PARTICULARS OF CONTRIBUTORS: 1. Senior Lecturer, Meghana Institute of Dental Sciences, Nizamabad, Andhrapradesh 2. Senior Lecturer, Meghana Institute of Dental Sciences, Nizamabad, Andhrapradesh 3. Professor & HOD, Meghana Institute of Dental Sciences, Nizamabad, Andhrapradesh 4. Professor, Meghana Institute of Dental Sciences, Nizamabad, Andhrapradesh 5. Reader, Meghana Institute of Dental Sciences, Nizamabad, Andhrapradesh.

NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR: Dr. Asma Qureshi, Date of Submission: Sep 21, 2013 Meghana Institute of Dental Sciences, Nizamabad, Andhrapradesh. Date of Peer Review: Dec 03, 2013 Phone: 07893191667, E-mail: [email protected] Date of Acceptance: Dec 13, 2013 Date of Publishing: Jan 12, 2014 Financial OR OTHER COMPETING INTERESTS: None.

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