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Journal of Dental Research

DOI: 10.1177/00220345750540021401 1975; 54; B176 J DENT RES

Robert M. Frank Reactions of Dentin and Pulp to Drugs and Restorative Materials

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DENTIN-PULPH. R. MUHLEMANN, moderator



Reactions of Dentin and Pulp to Drugs andRestorative Materials

ROBERT M. FRANK

Research Center, Faculty of Dental Surgery, Strasbourg, France

The reactions of dentin and pulp to drugsand restorative materials are mainly the con-sequence of the tissue destruction inducedby dental caries. Through improvementsin technology, many new products are de-veloped in dentistry and it is essential toknow precisely their behavior toward thedental tissues. Hundreds of papers havebeen devoted to the biological testing ofdrugs, liners, varnishes, bases, and fillings.Precise methodological rules have been rec-ommended for their experimental evalua-tion. In addition to the study of the pulp,attention has been focused, in recent years,on the reaction of the inorganic part as wellas of the cytoplasmic and organic compo-nents of dentin.

Structure of Normal Pulp and DentinThe prominent pulpal cells are the fibro-

blasts and the fibrocytes. Great variationsin cell density can be observed. The fibro-blasts are slender bipolar cells containing awell-differentiated Golgi complex and endo-plasmic reticulum closely associated with mi-tochondria.1 The fibrocyte is characterizedby a scarcity of organelles. Besides theseprominent cell types, normal human pulpcontains only a few macrophages, plasmo-cytes, mast cells, and leukocytes.The intercellular substance filled with

ground substance contains two types offibrous elements. Collagen fibrils are dis-seminated as discrete bundles within theground substance. With increasing age, col-lagen fibrils become more prominent. Be-sides the collagen, small nonstriated fila-ments, 150 A in diameter, sometimes groupedin bundles, are considered to be similar tothe so-called oxytalan fibrils of the perio-dontal membrane.',2The blood vessels of the pulp consist

B176

mainly of numerous capillaries connectedwith arterioles and venules. Many neuralelements follow the pathways of the largervessels which have a thin layer of musclecells surrounding the endothelium-linedtubes. Two types of blood capillaries arelocated in the dental pulp. Capillaries withcontinuous thick or thin endothielial liningare surrounded by a basement membraneand crowns of pericytes. They were seenalternating with fenestrated capillaries.'These have thin endothelial cells and shownumerous pores about 600 A in diameterand were found in regions where importantand fast liquid exchanges occur. Thesefenestrated capillaries contribute to a fastercontrol of hydremia and electrolyte balancebetween the intravascular compartment andthe interstitial tissue. Riedel, Fromme, andTallen3 and Kukletova4 have claimed tohave identified lymphatic capillaries in thepulp under the electron microscope. Suchlymphatic capillaries had open walls witlhtheir vessel lumens communicating directlywith the surrounding connective tissue.The subodontoblastic layer is classically

constituted by the acellular Weil's zone, lo-cated along the odontoblasts, and a cell-richlayer described by Gotjamanos.5 However,the acellular zone can be absent in normaladult pulps and a cell-rich layer is theninterposed between the odontoblasts and thepulpal tissue.1

All nerve fibrils penetrating in the pulpthrough the apical region are surrounded bySchwann cells. The myelinated nerve fibrilshave a rounded or folded myelin sheath.'The myelin sheath surrounds the axon. Abasement membrane, located on the externalcell membrane of the Schwann cell, limitsthe myelinated fiber.

Several amyelinated nerve fibrils are in-



DENTIN AND PULP REACTIONS B177

vaginated within the cytoplasm of a Schwanncell. The plasma membrane of this lattercell constitutes typical mesaxons. A basementmembrane is seen around the amyelinatednerve fibrils, which are more numerous near

the subodontoblastic layer of the pulp cham-ber. In the plexus of Raschkow, both types

of nerve fibers can be seen loosing theirSchwann cell covering and their basementmembrane, and close contacts between fibro-blasts and odontoblasts have been observed.0Myelinated fibers can also loose their myelinsheaths.6 In the coronal dentin, some nerve

fibers pass between the odontoblasts andreach the predentin and inner dentin.The odontoblasts in normal adult dentin

may have different ultrastructural aspects.

When engaged in secretory activities, thecell has a well-developed Golgi zone lo-cated along the dentinal side of the nucleuswith different types of vesicles, vacuoles, andelongated and multivesicular bodies. ThisGolgi zone is surrounded by a rich endo-plasmic reticulum with numerous mito-chondria containing dense calcium granules.Microfilaments and microtubules are dis-seminated in the cytoplasm. When engagedin catabolic activities, large lysosomelikestructures are visible within the odontoblastwhich can also take the aspect of a restingcell with just a few organelles. The lateralsurfaces of these cells are connected by des-mosomes, whereas toward the predentin thesesurfaces are attached by a junctional com-

plex consisting of a desmosome, an inter-mediary junction, and a tight junction lo-cated near the predentin. In tile lateralintercellular spaces, some collagen bundlesas well as some nerve fibers can be observed.The odontoblast process, a cellular ex-

tension of the odontoblast, extends throughpredentin and dentin. Brannstrom andGarberoglio,7 through use of a scanning elec-tron microscope, observed that these pro-

cesses in young human premolars were onlyfound within a distance from the pulp equal-ing about one-quarter of the total length ofthe tubule. With transmitted electron micros-copy,8 most of the dentinal tubules near thehuman dentinoenamel junction showed ab-sence of odontoblastic processes; however, inyoung human premolars, hyaline peripheraldegenerescence of these processes was ob-served.Bound by a plasma membrane, the cyto-

plasmic process at the level of predentinand inner dentin contains numerous micro-tubules and microfilaments with few or-ganelles. Elongated small granules, associatedwith transfer of collagen9'10 and ground sub-stance precursors"l during dentinogenesis,are rarely seen in adult dentin. In the latter,large vacuoles with light or dense contents,which seem to be associated either withexocytosis or endocytosis,12 are observed atdifferent levels of the odontoblast and itsprocess. At the peripheral extremity of theprocess, centrally located large vacuoles, withlight cores, are associated with a hyalinecytoplasmic degenerescence of the process.13Lateral cytoplasmic processes penetrate inlateral b)ranching of the tubule.The odontoblast process does not fill the

tubular lumen and between the odontoblastprocess and the calcified wall of the tubule,a periodontoblastic space is visible.'3 Inthe inner dentin, it contains a few un-calcified collagen bundles in areas where thetubular walls are made up by intertubulardentin. In addition, this space as well as theperipheral lumen of the tubules devoidedof odontoblast process (dead tracts) are filledwith the so-called dentinal fluid,14 whichlhas the composition of interstitial fluid.15"16The odontoblast process is suspended in thisfluid phase.At a certain distance from the predentin-

dentin border, the wall of the dentinaltubule is made up of hypercalcified peri-tubular dentin, which, in comparison to in-tertubular dentin, contains more minerals,fewer collagen fibrils, and more ground sub-stance. Even in normal conditions, thedentinal lumen can be completely occludedby apatitic mineralization.9 This dentinalsclerosis, also observed in transparent dentinduring the carious process,17 also can occur,in this latter case through deposition ofrhombohedral crystals consisting of PCa3-(P04) 2 whitlockite.18 It is important tonote that in an area of dentinal sclerosis, alltubules are not occluded and some scatteredlumens remain permeable.17

In recent years, important progress hasbeen made in the understanding of the mor-phological basis of dental innervation. Themost convincing evidence for dentin inner-vation using light microscopy has been estab-lished by Fearnhead,19 and recently con-firmed by Kerebel20 and Langeland, Yagi,

Vo 1 54 1975



J Dent Res Special Issue B

and Langeland.21 With the electron micro-scope, unmyelinated nerve fibers have beenlocated in the inner third of fully formedcoronal dentin in humans,'.7,'3.22,23,26 inmice,24 white rabbits,25 cats,6 and fish.6Presence of complex tight junctions betweenthe nerve fiber and the odontoblast process,with many attributes of synaptic or trans-ducer sites, has been described.23,26 In addi-tion, unmyelinated axons surrounded bySchwann cells23,24 and myelinated fibers23have been observed in tubules of innerdentin.

Controversial data have been obtainedfrom electrophysiological investigations con-cerning the presence of intradentinal recep-tors.27 Scott28 recorded electrical activitywhich according to him originated in theinner dentin of cat canines. However,Matthews29 thought that the recorded ac-tivity was conducted through the dentinfrom nerves located in the underlying pulpof the cat. In fact, conclusive evidence hasnow been presented about the intradentinalpresence of sensitive neurons. With thelight microscope Christensen30 showed thatnearly all nerve fibers in the pulp disap-peared after sectioning of the fifth nerve inthe cat but removal of the sympathetic su-perior cervical ganglion caused no appreci-able change in the pulpal nerve distribution.Fearnhead,'9 after resection of the inferiordental nerve in a green monkey, observedin the light microscope, after one month,the disappearance of the plexus of Raschkowand the intradentinal beaded nerves. Afterresection of the inferior alveolar nerve, de-generescence or absence of the unmyelinatedpredentinal and dentinal nerve fibers wasnoted under the electron microscope inmice,30 white rabbits,25 and cats,3' togetherwith a total absence of nervous activity afterelectrophysiological recordings.31Absence of nerves near the enamel-den-

tinal junction and the outer part of dentinis generally recognized,8,9,19,28 althoughthese areas are known to be clinically highlysensitive. Strong evidence has been pre-sented through numerous in vitro and invivo experiments that transmission of painstimuli to intradentinal and pulpal nervesare mediated through a hydrodynamiclink.32,33 A rapid outward flow in the den-tinal tubules can produce an immediatesharp pain that can be elicited by most

stimuli such as drilling, probing, air blasts,and cold.33 A second type of pain sensationis that which may be elicited by heat. Therequired stimulus for this response is an ex-tensive inward movement of the tubulecontents.33

Evaluating Dentin and Pulp Reactionsto Drugs and Materials

The evaluation of the dentin and pulpalreactions to drugs and materials is the finaltest required in the step-by-step proceduredeveloped by the US Department of Health,Education, and Welfare.34 Such a biologicevaluation is quite difficult to aclhieve be-cause of the great variability in the param-eters involved and standardization of the ex-perimental procedures appears as a neces-sity.35-37

Generally speaking, the dental tissue re-actions of new products are initially testedin animal teetlh, followed by experiments onhuman teeth. UJsually, intact teeth from rats,dogs, primates, and miniature pigs are used,but if healing properties of druigs or mate-rials are to be tested, an experimental pulp-itis system can be useful.38

In human teeth, age differences seem tohave no discernible effect on pulp re-sponse36; however, most authors preferablyuse noncarious human premolars of youngpatients, 12 to 15 years old, to be extractedfor orthodontic purposes. Ideally, four pre-molars in one patient are tested in twocrossed pairs; one tooth in each pair drawnby lots is filled with a control material. Usu-ally one cavity is prepared in one tooth, butMjor39 used buccal and lingual preparationsto estimate the reaction on the same pulp.The methods of cavity preparation also mustbe standardized. Most authors prepare buc-cal Class V cavities with low speeds andabundant cooling with water spray. An ex-tremely critical factor in pulp response isthe remaining dentin thiickness36 which can-not be controlled accurately during cavitypreparation. The dentin thickness has to bemeasured on the histological sections.

Important variables in assessments of den-tin and pulp reactions are related to the his-tological technique used. Special care mustbe taken in the fixation, demineralization,and staining procedures. Serial sectionshave to be examined. In understanding den-tin alterations, it must not be forgotten that

B178 FRANK




peritubular dentin and sclerosed tubularlumen are dissolved during acid or ethylene-diaminetetraacetic acid treatment. There-fore, special techniques such as microradiog-raphy, transmitted and scanning electronmicroscopy, and electron microprobe anal-ysis, may be indicated to study reactions inthe dentinal tubules.Adequate differentiation must be made

between normal histological variations,40 re-action caused by cavity preparation, and thatcaused by the drug or material itself. Dif-ferent types of criteria have been used toestimate the severity of pulpal reactions tomaterials, which in most instances follow infact a relatively uniform evolution. For ex-ample, Stanley36 used three histopathologicalcharacteristics based on odontoblast andleukocyte displacements in dentinal tubules,importance of the inflammatory cell infil-trate in the superficial and deeper pulpaltissue, and the predominating inflammatorycell. Holz and Baume4l paid special atten-tion to the state of the odontoblast processesin the dentinal tubules of the cavity floorand based their study on four criteria con-sisting of odontoblast aspects, secondary den-tin formation, pulpal degenerescence, andinflammatory response. In fact, almost everyauthor used his own technique for the ratingof pulpal reactions.

In most experiments, postoperative pe-riods of short and long durations have beenused, but here again great variations arenoted between different studies. Langeland37observed inflammatory changes at the pulp-dentinal junction as early as three hours.Short-term experiments may give misleadingresults in that they do not allow adequatetime for the recuperative powers of thedental pulp to reach their full expression.The great importance of long-term experi-ments must be emphasized. Following therepair of dental pulp after cavity prepara-tion up to 21 months, Marsland andShovelton42 noticed that repair occurred inthe pulp with deposition of an importantlayer of secondary dentin by new odonto-blasts differentiated from the less specializedcells of the pulp after destruction of theoriginal odontoblast lining. We agree withthese authors42 when they state that the con-demnation of a filling material is not justi-fied if it produces a localized pulpitis in ayoung, sound tooth after a few days. It will,

however, warrant rejection if it consistentlyproduces important pulp lesions after 200days. One of the main pulpal functions isdentinogenesis; therefore, new formation ofdentin under a filling should be consideredas biologically satisfactory. Several stud-ies43,44 using tritiated thymidine haveshown that after initial odontoblast de-generescence, new odontoblasts can be dif-ferentiated from spindle-shaped cells of thepulp.

If pulpal-dentinal lesions can result fromthe action of drugs or fillings, irritationsthrough salivary or bacterial infiltrationsalong the cavity walls can also play an im-portant role. Marginal leakage has beendemonstrated through percolation and dif-fusion of different dyes or radioisotopes, aswell as through observations with reflectedlight microscopy and scanning electron mi-croscopy. Recently Brannstrom and Ny-borg45 have even assumed that diffusion ofbacteria trapped in cavity walls before res-toration or entering through marginal leak-age, rather than the chemical irritation byfillings, may be the main cause of pulpal in-flammation. Accordingly, they recommendthat the test and control cavities be cleanedwith a microbicidal solution.45

Dentin and Pulp Reactions to DrugsMost drugs and substances applied to den-

tin, with the possible exception of diluteadenocorticotropic hormone and cortisonederivatives, produce an inflammatory reac-tion within the pulp. All fat solvents suchas ether, chloroform, xylol, and acetone pro-duce severe reactions to odontoblasts and aremost irritating.46 Some essential oils, suchas eugenol, are if anything at least nonreac-tive. Phenol penetrates dentin easily and ishighly irritative.46 Hydrogen peroxide ap-plied to dentin caused an inflammatory re-action in intact pulp and did not reduce anexisting inflammation.47

Silver nitrate, often used as a cavitysterilization or desensitizing agent, is able topenetrate the dentinal tubules of primaryand secondary dentin.47 Silver nitrate gran-ules have been observed as early as five min-utes after its use at a distance of 50 microm-eters in the odontoblast process.41 A micro-bicidal cavity cleanera containing chlorhexi-dine and dodecyldiaminoethyl glycine in a

a Tubulicid, Dental Therapeut. A.B., Nacka, Sweden.

Vol1 54 1975




3% sodium fluoride solution, applied forfive seconds after cavity preparation, wasclaimed to eliminate all bacteria remainingon the walls without an irritating pulpaleffect.45Camphorated parachlorphenol, when ap-

plied to dentin, produced pulpal inflamma-tion.47 It could be shown that this drug aswell as eugenol and Formocresol destroyedlysosome fractions prepared from bovinepulp.48 A radioautographic comparison ofthe dentin penetration of tritiated aqueousparachlorophenol and camphorated para-chlorophenol placed in the pulp chamberand root canal showed that the first solutionpenetrated the dentin and reached thecementodentinal junction, whereas the cam-phorated parachlorphenol did not.49Topical fluoride solutions have been ap-

plied to freshly prepared dentin cavities forremineralization of carious tissue and forreduction of recurrent marginal caries. Re-mineralization was demonstrated in vitrowith a 10% stannous fluoride solution50 aswell as a reduction in acid solubility ofdentin treated with a 2% sodium fluoridesolution.5' Stannous fluoride applied tofreshly cut dentin or to the exposed pulptissue produced no adverse effects in rats,52,53dogs,54 or primates.55 By diffusion of sodiumfluoride, stannous fluoride, and acidulated-phosphate fluoride solutions through denti-nal disks onto monolayers of marmoset gin-gival fibroblasts, no cytotoxic effects werenoticed at clinically used concentrations andexposure times.56 No harmful effects onhuman pulps were observed after a 2% so-dium fluoride treatment of experimentallyprepared cavities for two minutes.57

Cervical root hypersensitivity has beentreated with sodium fluoride and other com-pounds containing fluoride. Microradiog-raphy and electron microscopic studies ofhypersensitive dentin with CaHPO4 showedmineral deposition and sclerosed dentinaltubules.58 Some workers have attempted toenhance chemical penetration by using ion-tophoresis. lontophoresis was effective whenused either with or without a fluoride den-tifrice,59 but a placebo effect was demon-strated in the control group. A desensitizingeffect also was observed with a calcium hy-droxide paste.60

Finally, it must not be forgotten that low

molecular weight medicaments commonlyused in contact with viable pulp may serveas haptens. Immunologic sensitizationthrough pulp canals in rabbits6i and pri-mates62 has been demonstrated.

Pulp Capping AgentsNumerous pulp capping agents hiave been

used, but the ideal remedy has not beenfound. Calcium hydroxide preparations aremost widely used but seem to have theirlimitations. Despite the opinion of Lange-land and Langeland,63 convincing evidenceindicates that calcium hydroxide will in-crease the density, hardness, and mineralcontent64,65 of underlying carious dentin inprimary and permanent teeth. It sterilizesthe residual deep layer of caries66 and pro-duces secondary dentin deposition.67 With45Ca, it has been shown that calcium liy-droxide did not participate directly in theformation of reparative dentin.68 In com-parative studies, zinc oxide and eugenol(ZOE) was thought to be as effective ascalcium hydroxide for covering residual car-ies.69,70 However, no visible change couldbe demonstrated through microradiographyin ZOE-covered dentin.65

Different types of calcium hydroxidepreparations are commercially available:Pulpdentb is suspended in methyl cellulose,whereas Hydrexc and Dycald contain resins.Controversial evaluation has been made ofthese materials as base materials, especiallyunder composites. Whereas Tronstad andMjdr7l found all of these three products ac-ceptable, Holz and Baume4l obtained un-satisfactory pulpal reactions with Pulpdentand Hydrex. This latter product gave goodprotection under a composite according toLangeland, Dogon, and Langeland.72 How-ever, Sekine and others,73 testing differentcalcium hydroxide preparations, obtainedthe worst results with Hydex and the bestwith Calvital.e

Direct pulp capping with calcium hydrox-ide on pulp exposures seemed to produce anirregular calcified bridge caused by calcifica-tion of collagen produced by fibroblastsfollowed by a regular dentin bridge.74.75However, Langeland37 cast some doubts on

b Rower Dental Mfg. Corp., Boston, Mass." Kerr Mfg. Co., Detroit, Mich.d L. D. Caulk Co., Milford, Del.e Neo Chemical Products Co., Japan.

B180 FRANK




the quality of the dentin bridge formed andunderlined the risk of residual chronicpulpal inflammation. Zinc oxide eugenolcement seemed to provide more favorablepulp healing than calcium hydroxide, butno complete dentin bridge formed.76 Clin-ical77 and experimental78 studies apparentlysubstantiated the efficacy of Dycal as a directpulp capping agent, whereas in pulp ex-posures of intact rat molars Hydrex pro-duced chronic inflammation and pulp ne-crosis.79

In pulpotomies, after sterile amputationof the coronal pulp and calcium hydroxideapplication on the pulp stumps, Schroderand Granath80 observed that in young hu-man premolars after one month a calcificbarrier was formed first by an irregular bone-like substance while the last one resembleddentin. In primary teeth, after pulpotomy,dressings of calcium hydroxide or Formalin-containing compounds have been recom-mended. They were evaluated in primaryand young permanent teeth of rhesus mon-keys.81 It seemed that the Formocresoltherapy gave results superior to the hydrox-ide pulp therapy. In incompletely formedpulpless teeth, the relationship of calciumhydroxide paste to continued root forma-tion and absence of inflammatory responsein the periapical tissues has been demon-strated in dogs.82

Indirect pulp capping with antibioticsdoes not seem to be adequate: dentinal ap-plication of penicillin47 or association withcamphorated paramonochlorphenol63 pro-duced pulpal inflammation. Studies withconventional and germfree rats demon-strated that the presence of bacteria is asignificant factor in prohibiting healing ofpulp exposures.83 The association of cal-cium hydroxide with vancomycinf as directpulp capping agents was more successfulthan calcium hydroxide alone.84 However,the single use of sodium cephalothin"proved to be too irritating for vital pulptherapy.78

Controversial results also have been ob-tained with corticosteroids used alone or as-sociated with antibiotics. When corticoste-roids were used for indirect pulp capping,suppression or reduction of pulpal inflam-mation without alteration of dentinogenesis

f Vancocin, Eli Lilly Co., Indianapolis, Ind.g Keflin, Eli Lilly Co., Indianapolis, Ind.

was observed by most authors85-87; in directpulp capping, persistent inflammation withincreased dentinogenesis63 or the absence ofdentin formation87'88 was noted. In germ-free animals,83 it is interesting to note thatapplication of corticosteroids is neither help-ful nor harmful to exposed pulp -healing.Most authors observed a persistent chronicinflammation of the pulp with a cortico-steroid-antibiotic preparationh in direct pulpcapping.63,87

Preliminary results seemed to indicate thatlyophylized89 or demineralized90 dentincould be better direct capping agents thancalcium hydroxide, antibiotics, or corti-costeroids.

Base Cements, Liners, and VarnishesA combination of ZOE is still widely used

for temporary fillings and protective basesunder permanent fillings. It has been statedthat ZOE, like zinc phosphate cement, canbe irritating in deep cavities; nevertheless,most testing experiments of materials useZOE as a control material.

Since ZOE has low compressive strength,different additives have been proposed toreinforce the original formulation. IRMi(a resin-reinforced ZOE), EBA,j Kalsogen,kand Cazil seemed to be biologically accept-able but also slightly more irritative thanZOE.41 ,91

It was thought that oxyphosphate cementsand copper cements were damaging to thepulp. According to Langeland,37 this isseemingly true for copper cements, but notfor oxyphosphate cements. It seemed thatthe reactions observed were due to overdry-ing of the cavity. Whereas Plant and Tyas92and Eriksen93 observed mild reaction withDropsin,m a modified zinc phosphate, Holzand Baume4' consider this cement as im-proper for pulpal protection.The polycarboxylate cement system, first

developed by Smith,94 consists of a modi-fied zinc oxide powder and an aqueous solu-tion of polyacrylic acid. Zinc phosphate andpolycarboxylate cements appear to havesimilar properties especially in setting time

h Ledermix, Lederle Arzneimittel, Cyanamid Gmbh,Munchen-Pasing, West Germany.

I L. D. Caulk Co., Milford, Del.J Opotow Dental Mfg. Co., Brooklyn, NY.k De Trey, Zurich, Switzerland.National Bureau of Standards, Washington, DC.

m Svedia, Enkoping, Sweden.

Vol1 54 1975




and pH,92 but the latter cement seemed tohave better biologic properties and bondingpotentials. As a base material on dentin oras luting agents, almost all reports95-100have mentioned mild pulpal reactions withDurelon.n Only Holz and Baume4' reporteddentin and pulp lesions and even pulp ne-crosis with Poly Co after 120 days.10'The intended effects of liners and var-

nishes are to protect the pulp from chemicalirritants of the restorative materials, to pre-vent marginal leakage and ingress of bac-teria, and to ensure thermal insulations. Acavity varnish is a natural gum such ascopal, resin, and synthetic resin dissolved inan organic solvent, whereas a cavity liner is aliquid in which calcium hydroxide or zincoxide or both are suspended in a solution ofnatural or synthetic resins. Going and Mass-ler102 found that copal resin varnishes, poly-styrene ethylcellulose liner, and calciumhydroxide liners were effective in preventingpenetration of radioactive ions into the den-tin and pulp. However, it must not be for-gotten that in vivo dentin surfaces arewet'4-'6 and therefore the application ofliners or varnishes may not lead to im-pervious sheaths.37'103

It was found that a vinyl copolymer linerPwas not adequate to protect pulp undercomposite fillings.104'105 Whereas Holz andBaume4' noticed favorable reaction withcyanoacrylate liners under amalgam fillings,this was not the case under composites.However, in dogs, Tobias et al'06 found thatthis type of liner was well tolerated andBerkman et al,107 using isobutyl cyanoacry-late as direct pulp capping agents on hu-man teeth, observed more even healing ofthe pulp with reparative dentin bridge for-mation and less inflammation than with cal-cium hydroxide preparations.A polystyrene linerq developed by Zander,

Glenn, and Nelson108 and modified byBrannstr6m and Nyborg45'109,110 was foundeffective in thick layers in protecting pulpunder amalgam, silicates, and compositeresins45,93,109-111 and seemed to be effectiveagainst microleakage.

* ESPE Co., Seefeld, West Germany.* Amalgamated Dental Trade Distr., Ltd., London,

Eng.P 3 M cavity liner, Dental Restorative System, 3 M,

St. Paul, Minn.q Tubulitec, Dental Therapeutics A/B, Sweden and

Buffalo Dental Mfg. Co., Brooklyn, NY.

Permanent Restorative FillingsAmalgam material, still widely used in re-

storative dentistry, is not considered injur-ious to the pulp but requires protection indeep cavities. Microleakage can be reducedwith the use of copal varnishes.4'

Despite certain inadequacies such aspulpal irritation, high solubility in oralfluids, poor resistance to abrasion and micro-leakage, silicates are still appreciated fortheir remarkable resistance to recurrent den-tal caries (probably due to their relativelyhigh fluoride content) and for their initialesthetic qualities. Recent investigations stillconfirmed the necessity for ptulpal protec-tion'01,'12 under silicates, even if improvedformulas were used.'0' However, no agree-ment has been reached about the cause ofthe harmful pulpal effects. 32p of silicatecement tagged with phosphoric acid canpenetrate the dentin of monkey's teeth inVivo113 and it could be shown with vitalmicroscopy, on the rat incisor pulp, thatsilicate liquid penetrated dentin with libera-tion of C02, producing vascular pulpalthrombosis.114 However, buffered phos-phoric acid solutions applied to Class Vcavities in human teeth produced similar in-flammatory changes as distilled water.1"15The toxic effects of silicate ions and of phos-phates and fluorides of calcium, aluminum,tin, and arsenic also were questioned. Thefact that direct application of silicates ondentin produced more severe lesions in hlu-man teeth after six months than after onemonth raised the problem of the poor seal-ing properties of silicates'16; the pulpaleffects were due either to mechanical perco-lation or to the presence of microorganismsbetween the filling and the cavity walls.With a polystyrene liner applied on thecavity floor and walls, the sealing propertieswere improved in deep silicate restorations,according to Briinnstrom and Nyborg.109

Cold-curing unfilled acrylic materials havebeen condemned because of severe pulpalinflammations and poor marginal adapta-tion, with risks of recurrent caries. Zincoxide and eugenol cement cannot be usedbecause of reactivity between eugenol andacrylic material.However, increasing clinical use has been

made of composite resins, based on theoriginal system of Bowen.117 It appearsthat direct application of these composites

B182 FRANK




in unlined dental cavities gave rise to mildbut persistent pulpal inflammation.44,72,104106,110,111 Zinc oxides are not compatiblewith composite materials because of dis-coloration of the restoration18 and someauthors think that calcium hydroxide basesare the preferable sealing product.72'105'106,118 Holz and Baume4l and Baume, Fiore-Donno, and Holz"19 found that liquid linersor varnishes offer insufficient pulpal pro-tection; they used modified zinc oxideeugenol cements, applying the compositesafter complete hardening of the base.1"9 Apolystyrene (Tubulitecr) reduced the irrita-tive pulpal reaction significantly but nottotally.1"' According to Brannstrom andNyborg,45 it is not the chemical irritants ofthe composite that are responsible for thepulpal reaction, but the toxins as a result oftrapped bacteria or ingrowth of microorgan-isms through microleakage. They apparentlyobtained satisfactory results with a micro-bicidal cleanser, Tubilicid, and a polystyreneliner (Tubulitec) before inserting the com-posite. Further evaluation of this procedureand consideration of the prevailing impor-tance of microleakage seem necessary.

Since enamel and dentin surfaces of acavity may be covered by debris, saliva, anddentinal fluid that exudes from cut tubules,an acid cleansing and etching treatment,which would facilitate the bonding of com-posite resins (Enamelites and Restodents)was recommended. According to Lee, Jr. etal,120 a treatment for one to five minuteswith 50% citric acid or 50% phosphoric acidproduces only a superficial dentin etchingwithout penetration of acids along tubules.It must be said that short treatment of in-tact enamel fissures with 50%, phosphoricacid followed by application of a fissuresealantt did not induce any pulpal reac-tion.121 The use of cavity cleansers on thewalls of dentin cavities seemed to inducemoderate to severe pulpal reactions.122-124The use of Enamelite, without prior etch-ing, in unlined Class V cavities in monkeys,produced mild inflammatory response.'25However, further biological evaluation ofthese products is necessary.

r L. D. Caulk Co., Milford, Del.8 Lee Pharmaceuticals, South el Monte, Calif.t Nuva-Seal, L. D. Caulk Co., Milford, Del.

ConclusionsBecause of the increased number of new

drugs and materials, biological tests withwell-standardized methodology are necessary.Important progress has been made in thefields of pulp capping agents, base materials,and permanent fillings. Almost all these ma-terials produce moderate to severe reactionsbecause of chemical irritation or of bac-terial toxins, or both, in contact with dentinand pulp. However, the control of dentinal-pulpal reactions must not become an aca-demic, histological exercise that loses thepoint of view of clinical dentistry. It is bio-logically evident that the contact of anydrug and material with cytoplasmic cellprocesses will induce odontoblastic altera-tions and transient inflammatory reactions.The purpose of biological testing is not tooverstate these normal reactions, but tocheck the recovery potentials of the pulpand the absence of persistent inflammation.

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115. JOHNSON, R.H.; CHRISTENSEN, G.L.; STIGERS,R.W.; and LASWELL, H. R.: Pulpal Irrita-tion Due to the Phosphoric Acid Compo-nent of Silicate Cement, Oral Surg 29: 447-454, 1970.

116. HANSEN, H.P., and BRUUN, C.: Long-termPulp Reaction to Silicate Cement with anIntradental Control, Scand J Dent Res 79:422-429, 1971.

117. BOWEN, R.L.: Dental Filling Material Com-prising Vinyl Sylane Treated Fused Silicaand a Binder Consisting of the ReactionProduct of Bis Phenol and Glycdyl Acry-late, US Patent 3066.112, Nov 27, 1962.

118. STANLEY, H.R.; SWERDLOW, H.; STANWICH,L.; and SUAREZ, C.: A Comparison of theBiologic Effects of Filling Materials withRecommendations for Pulp Protection, JAm Acad Gold Foil Oper 12: 56-62, 1969.

119. BAUME, L.J.; FIORE-DONNo, G.; and HOLZ,J. La reaction pulpaire a l1'gard dei'Addent XV et sa prevention, Rev MensSuis Odontol Stomatol 81: 1099-1120, 1971.

120. LEE, H.L., JR.; ORLOWSKI, J.A.; SCHElDT,G.C.; and LEE, J.R.: Effects of Acid Etch-ants on Dentin, J Dent Res 52: 1228-1233,1973.

121. SOMMERMATER, J., and FRANK, R.M.: Pre-vention de la carie par scellement des sil-lons dentaires, J Biol Buccale 2: 39-50, 1974.

122. GoTo, G., and JORDAN, R.E.: Pulpal Ef-fects of Concentrated Phosphoric Acid,Bull Tokyo Dent Coll 14:105-112, 1973.

123. ERIKSEN, H.M.: Pulpal Response of Mon-keys to Epoxylite CBA 9080 Resin Cement,J Dent Res 52: 992, 1973, (abstract) .

124. VOJINOVIC, O.; NYBORG, H.; and BRANN-STROM, M.: Acid Treatment of Cavitiesunder Resin Fillings: Bacterial Growth inDentinal Tubules and Pulpal Reactions,J Dent Res 52: 1189-1193, 1973.

125. RETIEF, D.H.; CLEATON-JONES, P.E.; andAusTIN, J: Pulpal Response to a New Com-posite Dental Restorative Material, J OralPathol 2: 215-221, 1973.

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