Pulpal Reaction to Caries

Dental caries is a localized, destructive, and progressive infection of dentin; if left unchecked, caries can result in pulpal necrosis and potential tooth loss. Both bacterial byproducts and products from the dissolution of the organic and inorganic constituents of dentin mediate the effects of dental caries on the pulp. Three basic reactions tend to protect the pulp against caries: (1) a decrease in dentin permeability, (2) tertiary dentin formation, and (3) inflammatory and immune reactions. These responses occur concomitantly, and their robustness is highly dependent on the aggressive nature of the advancing lesion.

In the advancing infection front of the carious lesion, multiple intrinsic and extrinsic factors are released that are stimulatory to subjacent pulpal parenchyma. Bacterial metabolites such as acids have been thought to be initiators of pulpal reactions, yet the buffering capacity of dentin fluid likely attenuates the pH before it can directly effect a deleterious response, except when the remaining dentin thickness is minimal.²¹⁴ When relatively unhindered access to pulpal tissue is present, both bacterial metabolites and cell wall components induce inflammation. In initial to moderate lesions, current evidence suggests that acidic byproducts of the carious process act indirectly by degrading the dentin matrix, thereby liberating bioactive molecules previously sequestered during dentinogenesis. Once liberated, these molecules once again assume their role in dentin formation, this time stimulatory for tertiary dentinogenesis.²¹⁶ This theory is supported by the findings that demineralized dentin matrix implanted at the site of pulpal exposure can induce dentinogenesis.²⁴³ Furthermore, placement of purified dentin matrix proteins on exposed dentin or exposed pulp stimulates tertiary dentin formation, indicating that these molecules can act directly or across intact dentin.^217,242

Recent evidence offers several candidate molecules that are stimulatory for reparative dentinogenesis. Heparin-binding growth factor, transforming growth factor (TGF)-β1, TGF-β3, insulin-like growth factors (IGF)-1 and -2, platelet-derived growth factor, and angiogenic growth factors have been shown to be stimulatory for dentinogenesis in vitro. The TGF-β superfamily in particular seems to be important in the signaling process for odontoblast differentiation as well as primary and tertiary dentinogenesis. As the predominant isoform, TGF-β1 is equally distributed in the soluble and insoluble fractions of dentin matrix.³⁹ During the carious dissolution of dentin, it is believed that the soluble pool of TGF-β1 can diffuse across intact dentin while the insoluble pool is immobilized on insoluble dentin matrix and serves to stimulate odontoblasts, much like membrane-bound TGF-βs during odontogenesis.²¹⁴

Despite the research interest in tertiary dentinogenesis, it is neither the first nor necessarily the most effective pulpally mediated defense against invading pathogens. A combination of an increased deposition of intratubular dentin and the direct deposition of mineral crystals into the narrowed dentin tubules to decrease dentin permeability is the first defense to caries and is called dentin sclerosis. It occurs by a combination of increased deposition of intratubular dentin and tubule occlusion by precipitated crystals. This results in an effective decrease in dentin permeability that occurs in a relatively short period of time. Classic studies have noted that while sclerosis is observed in the dentin of disease-free and attrition-free teeth, there is a 95% increase in the incidence in carious teeth.²²² In vitro studies with cultured tooth slices implicate TGF-β1 as a central player in the increased deposition of intratubular dentin.²¹³ The deposition of whitlockite crystals in the tubular lumen most likely results from a similar stimulation of vital associated odontoblasts, possibly in combination with precipitation of mineral released during the demineralization process^140,239 (Fig. 13-1).

FIG. 13-1 A, Whitlockite crystals occlude the dentinal tubules in sclerotic dentin. B, Dentinal sclerosis is radiographically apparent beneath a deep class II lesion.

(A from Yoshiyama M, Masada J, Uchida A, Ishida H: Scanning electron microscopic characterization of sensitive vs. insensitive human radicular dentin. J Dent Res 68:1498–1502, 1989.)

The formation of tertiary dentin occurs over a longer period than does that of sclerotic dentin, and its resultant character is highly dependent on the stimulus. Mild stimuli activate resident quiescent odontoblasts, whereupon they elaborate the organic matrix of dentin. This type of tertiary dentin is referred to as reactionary dentin and can be observed when initial dentin demineralization occurs beneath the noncavitated enamel lesion.¹³⁵ Mediators present during the carious process induce a focal upregulation of matrix production by resident odontoblasts. The resultant dentin is similar in morphology to physiologic dentin and may only be apparent due to a change in the direction of the new dentinal tubules (Fig. 13-2). In the aggressive lesion, the carious process may prove cytocidal to subjacent odontoblasts and require repopulation of the disrupted odontoblast layer with differentiating progenitors. The appearance of the resultant matrix is a direct reflection of the differentiation state of the secretory cells. This accounts for the heterogeneity of reparative dentin, where the morphology can range from organized tubular dentin to more disorganized irregular fibrodentin. Fibrodentin, owing to its irregular configuration and tissue inclusions, is more permeable than physiologic dentin²⁵² (Fig. 13-3).

FIG. 13-2 Reactionary dentinogenesis (TD); note the tubular morphology and the discontinuity of the tubules at the interface of secondary and reactionary dentin. Resident odontoblasts are still present.

FIG. 13-3 Reparative dentin; the strong stimulus of the impinging infection is cytocidal for odontoblasts. The resultant dentin is irregular with soft-tissue inclusions.

Although dentin can provide a physical barrier against noxious stimuli, the pulpal immune response provides humoral and cellular challenges to invading pathogens. In the progressing carious lesion, the host immune response increases in intensity as the infection advances. It has been shown that titers of T helper cells, B-lineage cells, neutrophils, and macrophages are directly proportional to lesion depth in human teeth.¹⁰⁷ The disintegration of large amounts of dentin, however, is not necessary to elicit a pulpal immune response. This is supported by the observation that a pulpal inflammatory response can be seen beneath noncavitated lesions and noncoalesced pits and fissures.³³

The early inflammatory response to caries is characterized by the focal accumulation of chronic inflammatory cells (Fig. 13-4). This is mediated initially by odontoblasts and later by dendritic cells. As the most peripheral cell in the pulp, the odontoblast is positioned to encounter foreign antigens first and initiate the innate immune response. Pathogen detection in general is accomplished via specific receptors called pattern recognition receptors (PRRs).¹⁰⁹ These receptors recognize pathogen-associated molecular patterns (PAMPs) on invading organisms and initiate a host defense through the activation of the nuclear factor (NF)-κB pathway.⁹¹ One class of the PAMP recognition molecules is the toll-like receptor family (TLRs). Odontoblasts have been shown to have increased expression of certain TLRs in response to bacterial products. Under experimental conditions, odontoblast expression of TLR3, 5, and 9 was increased in response to lipoteichoic acid, whereas lipopolysaccharide increased TLR2 expression.^59,166 Once the odontoblast TLR is stimulated by a pathogen, proinflammatory cytokines, chemokines, and antimicrobial peptides are elaborated by the odontoblast, resulting in recruitment and stimulation of immune effector cells as well as direct bacterial killing.⁶⁷

FIG. 13-4 The early pulpal response to caries is represented by a focal accumulation of chronic inflammatory cells. Note that peripheral to the inflammation, the pulpal parenchyma is relatively unaffected.

Many cells constitutively produce chemokines at low levels. Unstimulated odontoblasts express genes coding for CCl2, CXCL12, and CXCL14, three genes known to code for factors chemotactic for immature dendritic cells.⁴⁰ They also produce CCL26, a natural antagonist for CCR1, CCR2, and CCR5, which are chemokines normally produced by monocytes and dendritic cells.²⁶⁴ Stimulation with bacterial cell wall constituents has been shown to upregulate the production of several chemokines, suggesting that odontoblasts sense pathogens and express factors that recruit immune effector cells^40,136 (Fig. 13-5). These data suggest a scenario whereby stimulated odontoblasts express high levels of chemokines such as interleukin (IL)-8 (CXCL8) that act in concert with the release of formerly sequestered TGF-β1 from carious dentin, the result of which is a focal increase in dendritic cell numbers, with additional release of chemotactic mediators.⁶⁸ The subsequent influx of immune effector cells is composed of lymphocytes, macrophages, and plasma cells. This cellular infiltrate is accompanied by localized capillary sprouting in response to angiogenic factors, as well as coaggregation of nerve fibers and HLA-DR-positive dendritic cells.^257,258

FIG. 13-5 Odontoblasts exposed to lipopolysaccharide (LPS) in an in vitro culture model express interleukin 8 (IL-8), evidenced by immunostaining with anti-IL-8 antibodies.

As the carious lesion progresses, the density of the chronic inflammatory infiltrate, as well as that of dendritic cells in the odontoblast region, increases. Pulpal dendritic cells are responsible for antigen presentation and stimulation of T lymphocytes. In the uninflamed pulp, they are scattered throughout the pulp. With caries progression, they aggregate initially in the pulp and subodontoblastic regions, then extend into the odontoblast layer, and eventually migrate into the entrance to tubules beside the odontoblast process²⁵⁹ (Fig. 13-6). There are two distinct populations of dendritic cells that have been identified in the dental pulp. CD11c+ are found in the pulp/dentin border and subjacent to pits and fissures. F4/80+ dendritic cells are concentrated in the perivascular spaces in the subodontoblastic zone and inner pulp.²⁶⁴ CD11c+ dendritic cells express toll-like receptors 2 and 4 and are CD205 positive. F4/80+ dendritic cells have migratory ability. As they migrate from the central pulp, they increase in size and become CD86 positive. The close spatial relationship between odontoblasts and dendritic cells under the carious lesion have led to speculation that dendritic cells may play a role in odontoblast differentiation and/or secretory activity in the immune defense and dentinogenesis. Pulpal Schwann cells have also been shown to produce molecules in response to caries, which is indicative of the acquisition of the ability for antigen presentation.

FIG. 13-6 Dental caries stimulates the accumulation of pulpal dendritic cells in and around the odontoblastic layer.

(Courtesy Mats Jontell.)

Evidence suggests that odontoblasts also play a role in the humoral immune response to caries. Immunoglobulin (Ig)G, IgM, and IgA have been localized in the cytoplasm and cell processes of odontoblasts in human carious dentin, suggesting that these cells actively transport antibodies to the infection front.¹⁷¹ In the incipient lesion, antibodies accumulate in the odontoblast layer and with lesion progression can be seen in the dentinal tubules. Eventually this leads to a focal concentration of antibodies beneath the advancing lesion.¹⁷⁰

In the most advanced phase of carious destruction, the humoral immune response is accompanied by immunopathologic destruction of pulpal tissue. In animal studies where monkeys were hyperimmunized to bovine serum albumin (BSA), there was an observed increase in pulpal tissue destruction subsequent to antigenic challenge across freshly cut dentin.²⁰ These findings support the contention that antigen-antibody complex formation, in addition to various products of the inflammatory cascade, gives rise to a nonspecific response that, while designed to rid the body of pathogens, effects destruction of parenchymal tissues as well.

Neurogenic Mediators

Neurogenic mediators are involved in the pulpal response to irritants and like immune components; they can mediate pathology as well as the healing response (for a review see Ref. 43). External stimulation of dentin causes the release of proinflammatory neuropeptides from pulpal afferent nerves.³⁵ Substance P, calcitonin gene-related peptide (CGRP), neurokinin A (NKA), NKY, and vasoactive intestinal peptide are released and affect vascular events such as vasodilatation and increased vascular permeability. This results in a net increase in tissue pressure that can progress to necrosis in extreme and persistent circumstances. Stimulation of sympathetic nerves in response to the local release of mediators such as norepinephrine, neuropeptide Y, and adenosine triphosphate (ATP) has been shown to alter pulpal blood flow. Both receptor field studies and anatomic studies have shown sprouting of afferent fibers in response to inflammation.³⁵

Neuropeptides can act to modulate the pulpal immune response. It has been demonstrated that substance P acts as a chemotactic and stimulatory agent for macrophages and T lymphocytes. The result of this stimulation is increased production of arachidonic acid metabolites, stimulation of lymphocytic mitosis, and production of cytokines. CGRP demonstrates immunosuppressive activity, which is evidenced by a decrease in H₂O₂ production by macrophages and a diminution of class II antigen presentation and lymphocyte proliferation.

Substance P and CGRP are mitogenic for pulpal and odontoblast-like cells and thereby initiate and propagate the pulpal healing response.²³⁷ CGRP has been shown to stimulate the production of bone morphogenic protein by human pulpal cells. The result of such stimulation has been postulated to induce tertiary dentinogenesis.³⁷

As the carious lesion approximates the pulp, there is an acute exacerbation of the precedent chronic inflammation. This is characterized by an influx of neutrophils. The accumulation of inflammatory cells becomes marked when the infection front reaches tertiary dentin.^128,129,200 In the presence of severe pulpal inflammation, focal microabscesses form and eventually coalesce, leading to progressive pulpal necrosis (Fig. 13-7).

FIG. 13-7 Hematoxylin- and eosin-stained section of a dental pulp, displaying pulpal necrosis.

Pulpal exposure in primary and immature permanent teeth can lead to a proliferative response, or hyperplastic pulpitis. Exuberant inflammatory tissue proliferates through the exposure and forms a “pulp polyp” (Fig. 13-8). It is presumed that a rich blood supply coupled with ample lymphatic and oral drainage allows this proliferative response. Conventional root canal therapy or progressive vital pulp therapy is indicated.

FIG. 13-8 A proliferative response to caries in a young tooth, typically referred to as proliferative pulpitis, hyperplastic pulpitis, or pulp polyp.

(Courtesy Dr. Howard Strassler, University of Maryland.)

Correlation between Clinical Symptoms and Actual Pulpal Inflammation

From a clinical perspective, it would be most helpful to the clinician to be able to diagnose pulpal conditions from a profile of the patient’s presenting symptoms. If symptoms are not conclusive, a number of objective tests should aid the clinician in reaching a definitive diagnosis of the pulpal pathologic status. In actuality, such combinations of subjective and objective findings are frequently insufficient in reaching definitive diagnosis of the status of the dental pulp. This is particularly true in cases of vital inflamed pulp, where it is difficult for the clinician to determine clinically whether the inflammation is reversible or irreversible.

Many clinicians rely on painful symptoms to determine the status of the pulp. Several studies have examined this question in some detail. A number of classic studies were performed in which the subjective and objective clinical findings related to carious teeth were recorded prior to extracting the teeth and examining them histologically. The underlying hypothesis in these studies was that the more severe the clinical symptoms, the more intense pulpal inflammation and destruction was evident histologically. The findings of these studies revealed that in the vital pulp, clinical symptoms generally did not correlate with gross histomorphologic findings.^90,150,209 Furthermore, carious pulp exposure was associated with severe inflammatory response or liquefactive necrosis, regardless of symptoms (Fig. 13-9). These histologic changes ranged in extent from being present only at the site of the exposure to deep into the root canals.²⁰⁹ In a few studies, prolonged or spontaneous severe symptoms were associated with chronic partial or total pulpitis or pulp necrosis.^57,209 However, in these as well as other studies, it was common to find cases with histologic evidence of severe inflammatory responses, including partial necrosis, but little or no clinical symptoms—the so-called painless pulpitis.^{57,90,150,209} Based on these studies and more recent data, it was reported that the incidence of painless pulpitis that leads to pulp necrosis and chronic periradicular periodontitis is about 40% to 60% of pulpitis cases.¹⁴⁹

FIG. 13-9 Histologic photomicrograph of a molar with carious pulp exposure. The exposure had been capped but had failed, and the patient presented with symptoms. The photomicrograph shows an area of necrosis and extensive inflammation throughout the coronal pulp.

(Courtesy Dr. Larz Spangberg, University of Connecticut.)

Objective clinical findings are essential for determining the vitality of the pulp and whether the inflammation has extended into the periapical tissues. Lack of response to electric pulp testing is generally indicative that the pulp has become necrotic.^202,209 Thermal pulp testing is valuable in reproducing a symptom of thermal sensitivity and allowing the clinician to assess the reaction of the patient to a stimulus and the duration of the response. However, pulp testing cannot determine the degree of pulpal inflammation.^57,209 These studies show that irreversible pulpal inflammation can be diagnosed with some certainty only in cases where, in addition to being responsive to pulp testing, the pulp develops severe spontaneous symptoms. Pulp necrosis could be predictably diagnosed by a consistent negative response to pulp tests, preferably to both cold and electrical tests to avoid false responses.^190,191 Pulp necrosis could be verified by a test cavity and/or lack of hemorrhagic pulp tissue upon access preparation. It should be noted, however, that the latter sign should be assessed cautiously. Occasionally, the pulp space is very small, such as in older individuals with calcified canals, and hemorrhage upon access to the pulp may not be clinically appreciable. Conversely, cases with pulp necrosis and acute periapical infections may have hemorrhagic purulent drainage through the large pulp space upon access preparation, particularly after initial instrumentation.

The lack of correlation between the histologic status of the pulp and clinical symptoms may be explained by recent advances in the science of pulp biology. In the last few decades, studies have shown that numerous molecular mediators may act in synchrony to initiate, promote, and/or modulate the inflammatory response in the dental pulp. Without the use of very specialized staining techniques, the nature and quantity of these inflammatory mediators cannot be determined from histologic analysis. Many of these molecular mediators tend to reduce the pain threshold, either directly by acting on peripheral nerve cells or through promoting the inflammatory process. Thus a number of these mediators were shown to be elevated in human pulp diagnosed with painful pulpitis. These mediators include prostaglandins^47,204; the vasoactive amine, bradykinin¹³⁴; tumor necrosis factor alpha (TNF-α)¹²³; neuropeptides such as substance P,²⁹ CGRP, and NKA¹¹; and catecholamines.¹⁶⁷ In fact, it was even shown that when patients have painful pulpitis, the crevicular fluid related to the affected teeth has significantly increased neuropeptides compared to the levels in contralateral teeth.¹¹ In another study, trained volunteers had an incisor stimulated with a constant current threefold the threshold value for 90 seconds.¹⁰ This resulted in a significant increase in crevicular matrix metalloproteinase 8 (MMP8), one of the collagenases involved in tissue destruction.

It has also been determined that peripheral opioid receptors are present in the dental pulp,¹⁰⁸ and these could play a role in why many cases with irreversible pulpitis are asymptomatic. As noted before, carious teeth are frequently not associated with significant symptoms. However, they still have a significant amount of inflammation. The pulp in teeth with mild to moderate caries has increased neuropeptide Y⁶¹ and its Y1 receptor,⁶² compared to normal teeth. Neuropeptide Y is a sympathetic nervous system neurotransmitter and is thought to act as a modulator of neurogenic inflammation. Likewise, the levels of vasoactive intestinal peptide (VIP), although not its receptor VPAC1, seemed to increase in the pulp of moderately carious teeth.⁶⁰

With recent advances in molecular biology, efficient simultaneous detection of hundreds of molecular mediators by their gene expression has become a reality. Current research seeks to examine which genes are specifically expressed or upregulated in the pulp in response to the carious lesion. In this regard, preliminary studies have shown that various cytokines and other inflammatory mediators are upregulated underneath a carious lesion in a manner that correlates with the depth of caries.¹⁴⁷ Gene microarrays have been used in several studies to obtain an accurate mapping of candidate genes that show elevated expression in inflamed pulp, the odontoblastic cell layer.^148,176,177 Development of more accurate chairside diagnostic methods is potentially feasible, particularly sampling from crevicular fluid, dentinal fluid, or the pulp directly. For this reason, more research is needed to determine the key mediators that would predict survival or degeneration of the dental pulp in difficult diagnostic cases.

Dentin Hypersensitivity and Its Management

Dentin hypersensitivity represents a special situation in which a significant, usually chronic, pulpal problem arises that does not seem to be associated with irreversible pulpal pathosis in the majority of cases. Dentin hypersensitivity is characterized by short, sharp pain arising from exposed dentin in response to stimuli—typically thermal, evaporative, tactile, osmotic, or chemical—that cannot be ascribed to any other form of dental defect or pathology.⁹⁴ Facial root surfaces in canines, premolars, and molars are particularly affected, especially in areas of periodontal attachment loss. Dentin hypersensitivity may be related to excessive abrasion during tooth brushing, periodontal disease, or erosion from dietary or gastric acids^2,3,44 and may be increased following scaling and root planning.^44,251 The dentin is hypersensitive most likely due to the lack of protection by cementum, loss of smear layer, and the hydrodynamic movement of fluid in dentinal tubules.^4,31 The degree of inflammation in the pulp in cases of dentin hypersensitivity is not well characterized because the condition is usually not severe enough to warrant tooth extraction or endodontic therapy. However, patent dentinal tubules are present in areas of hypersensitivity²⁶¹ (Fig. 13-10) and may result in increased irritation and localized reversible inflammation of the pulp at the sites involved.

FIG. 13-10 A, Scanning electron microscope (SEM) image of an exposed dentin surface of a hypersensitive area. A large proportion of dentinal tubules (arrows) are seen to be open. B, SEM image of a fractured dentinal tubule of a hypersensitive area. The lumen of the dentinal tubule is partitioned by membranous structures (arrow). C, SEM image of exposed dentin surface of a naturally desensitized area. The lumens of dentinal tubules (arrows) are mostly occluded, and the surface is extremely smooth. D, SEM image of a fractured dentinal tubule of a naturally desensitized area. Rhombohedral platelike crystals of 0.1 to 0.3 µm (arrow) are present.

(From Yoshiyama M, Masada J, Uchida A, Ishida H: Scanning electron microscopic characterization of sensitive vs. insensitive human radicular dentin. J Dent Res 68:1498, 1989.)

The application of neural modulating agents such as potassium nitrate¹⁴⁶ or tubule blocking agents such as strontium chloride, oxalates, or dentin bonding agents (Fig. 13-11)^4,184 usually alleviates the condition, at least temporarily. However, the placement of passive molecules or crystals may provide only temporary relief, so there has been a need to provide biocompatible materials that bond to the root surface to provide a more lasting solution. One such material was a calcium sodium phosphosilicate bioactive glass,¹⁴¹ which was developed into a commercial product (SootheRx, NovaMin Technology Inc, Alachua, FL). Another product uses a combination of a calcium oxalate and an acid-etched bonding material to seal the dentinal tubules (BisBlock, Bisco Inc, Schaumberg, IL). A concern has been raised that the acidic pH during etching may cause dissolution of the oxalate crystals, thus interfering with the effectiveness of the material.²⁵⁶ However, a recent study found that BisBlock and two other products (Seal&Protect, DENTSPLY DeTrey GmbH, Konstanz, Germany, and Vivasens, Ivoclar Vivadent AG, Schaan, Liechtenstein) were effective several weeks after treatment, compared to placebo.¹⁸⁰ In the long term, the development of smear layer, such as from tooth brushing, dentin sclerosis, reactionary dentin, and the blockage of tubules with large endogenous macromolecules are all thought to reduce the problem¹⁸³ (illustrated by Mechanism of Dentin Hypersensitivity animation on the Expert Consult Site).

FIG. 13-11 Smear layer treated with 30% dipotassium oxalate for 2 minutes plus 3% monopotassium and monohydrogen oxalate for 2 minutes. Dentin surface is completely covered with calcium oxalate crystals (×1900).

(From Pashley DH, Galloway SE: The effects of oxalate treatment on the smear layer of ground surfaces of human dentine. Arch Oral Biol 30:731, 1985.)

Pulpal Reactions to Local Anesthetics

An intact pulpal blood flow is critical for maintaining the health of the dental pulp. Because the dental pulp is enclosed in a rigid chamber and supplied by few arterioles through the apical foramina, it cannot benefit from collateral circulation or volumetric changes that compensate for changes in blood flow in other soft tissues. Furthermore, reduction in blood flow has the compounding effect of reducing the clearance of large molecular-weight toxins or waste products,¹⁸⁵ thus causing irreversible pulpal pathosis. Vasoconstrictors are added to local anesthetics to enhance the duration of anesthesia. However, vasoconstrictors in local anesthetics could negatively impact the health of the pulp if they reduce blood flow, particularly if the pulp is inflamed preoperatively. Earlier studies have documented that vasoconstrictors in local anesthetics do reduce pulpal blood flow in experimental animals when administered by infiltration and nerve block¹¹⁸ (Fig. 13-12), and that this effect was more severe with periodontal ligament injections¹¹⁷ (Fig. 13-13). More recently, clinical trials were conducted in which subjects were given infiltration of different local anesthetics with or without epinephrine at a concentration of 1:100,000, and the pulpal blood flow was measured by laser Doppler flowmetry. In groups that received the epinephrine, there were consistently significant reductions in pulpal blood flow,^5,46,160 even if the infiltration was palatal to maxillary premolars.¹⁹³ Interestingly in one study, the reduction in pulpal blood flow with epinephrine infiltration was more than the reduction in gingival blood flow and did not return to baseline values after 1 hour of injection.⁵ Similar reductions in pulpal blood flow were reported when inferior alveolar nerve block injections of lidocaine and 1:100,000 or 1:80,000 epinephrine were administered.¹⁶⁹ It is important to note a limitation of studies using laser Doppler flowmetry: a large proportion of the signal measured may be from sources other than the dental pulp.^192,219 Thus the monitoring of minor changes in pulpal blood flow must be interpreted with caution, particularly if the rubber dam or a similar barrier was not used.⁸⁹ Human studies on the effects of periodontal ligament or intraosseous injections on pulpal blood flow are unavailable, but from animal studies, it is probable that these supplemental anesthetic techniques cause more severe reduction or even transient cessation of pulpal blood flow. It was also shown that intraosseous injection of Depo-Medrol (a corticosteroid) in patients with symptomatic irreversible pulpitis causes significant reduction of prostaglandin E2 in the pulp 1 day after administration, indicating that this route of injection results in significant permeation into the pulpal tissues.¹⁰⁴ Taken together, these findings suggest that local anesthesia may compromise the inflamed pulp’s ability to recover from inflammation, particularly if it is severely inflamed, if the tooth is subjected to extensive restorative procedures, or if the anesthetic is delivered via a periodontal ligament or an intraosseous route. However, it is important to realize that this hypothesis should be supported or refuted by prospective randomized clinical trials.

FIG. 13-12 Effects of infiltration anesthesia (i.e., 2% lidocaine with 1:100,000 epinephrine) on pulpal blood flow in the maxillary canine teeth of dogs. There is a drastic decrease in pulpal blood flow soon after the injection. Arrow indicates the time of injection. Bars depict standard deviation.

(From Kim S, Edwall L, Trowbridge H, Chien S: Effects of local anesthetics on pulpal blood flow in dogs. J Dent Res 63:650, 1984.)

FIG. 13-13 Effects of ligamental injection (i.e., 2% lidocaine with 1:100,000 epinephrine) on pulpal blood flow in the mandibular canine and premolar teeth of dogs. Injection was given in the mesial and distal sulcus of premolar teeth. Injection caused total cessation of pulpal blood flow that lasted about 30 minutes in the premolar teeth. Arrow indicates time of injection.

(From Kim S: Ligamental injection: a physiological explanation of its efficacy. J Endod 12:486, 1986.)

Intrapulpal anesthesia is often used as a last resort when pulpal anesthesia is insufficient during root canal therapy. The effect of intrapulpal anesthesia on the pulp in these cases is not considered, since the pulp will be removed. However, occasionally a pulpotomy is performed to maintain pulpal vitality, such as in children, where the tooth has an immature apex. One study has shown that intrapulpal anesthesia can be used in these cases, with no clinical differences on follow-up of over 24 weeks between the groups that did or did not receive intrapulpal anesthesia, and when given, in the groups where the anesthetic contained or did not contain epinephrine.²³³

Pulpal Reactions to Restorative Procedures

A voluminous body of literature exists on the effects of restorative procedures on the dental pulp. This topic understandably has been important for practicing dentists for many years. Restorative procedures are performed primarily to treat an infectious disease—dental caries—which itself causes significant irritation of the pulp. They may also be performed to help restore missing teeth, correct developmental anomalies, address fractures, cracks, or failures of previous restorations, or a myriad of other abnormalities. One key requirement of a successful restorative procedure is to cause minimal additional irritation of the pulp so as not to interfere with normal pulpal healing. When pulp vitality is to be maintained during a restorative procedure, a provisional diagnosis of reversible pulpitis (rather than irreversible pulpitis) must preexist. Therefore, it would be most desirable to perform a minimally traumatic restorative procedure that would not potentially convert the diagnosis to irreversible pulpitis. As was discussed previously, irreversible pulpitis may present clinically with severe spontaneous postoperative pain, but it may also be asymptomatic, leading to the quiet demise of the pulp. The additive effects of restorative procedures are particularly critical in borderline cases, such as those of mildly symptomatic teeth with deep caries but no pulp exposure. There are still many factors whose influence on the response of the dental pulp to cumulative effects of caries, microleakage, restorative procedures, and materials is not well understood. It is generally accepted that the effects of pulpal insults, be they from caries, restorative procedures, or trauma, are cumulative. That is, with each succeeding irritation, the pulp has a diminished capacity to remain vital.

As a part of informed consent, the clinician is often faced with the task of outlining possible risks of restorative treatment. The question of the fate of pulps beneath single unit metal-ceramic (MC) crowns or MC bridge abutments was addressed.⁴⁵ Patients who had received either treatment from 1981 to 1989 at the Prince Philip Dental Hospital in Hong Kong were randomly selected and invited to attend a recall appointment that involved both clinical and radiographic examinations. One hundred twenty-two teeth with preoperatively vital pulps treated with single unit MC crowns and 77 treated as bridge abutments were examined. The mean observation period was 169 months for the former and 187 months for the latter. Pulpal necrosis had occurred in 15.6% of the teeth treated with single unit crowns after 10 years, while 32.5% of the pulps in the bridge retainer groups had become necrotic. There was a significantly higher percentage of pulpal necrosis in anterior teeth that served as bridge abutments (54.5% of anterior abutment teeth examined). In general, however, the available evidence indicates that the effects of dental procedures on the pulp depend on several key factors discussed in the following sections.

Degree of Physical Irritation Caused by Procedure

The physical irritation of the pulp during restorative procedures, such as from heat, desiccation or vibration, may adversely affect the dental pulp.

Heat

Restorative procedures such as cavity preparation, crown preparation, or curing of resins during direct fabrication of provisional restorations²³⁴ may cause significant increases in pulpal temperatures. It has been shown using primate models that an intrapulpal temperature rise of 10° C causes irreversible pulp pathosis in 15%, and a 20° C rise caused pulp abscess formation in 60% of teeth evaluated.²⁶² A number of other older studies documented burns or severe inflammation in the pulp when cavity or crown preparations were performed without coolants (Figs. 13-14, 13-15, 13-16). However, a study, in which gradual controlled heat application over a large area of the intact occlusal surface of human unanesthetized teeth was employed, failed to corroborate these earlier findings.¹² In this study, an increase of intrapulpal temperature of about 11° C, followed for 2 to 3 months of evaluation, did not induce any clinical or histologic changes in the pulp of any of the teeth evaluated. Heat increase in rat pulp tissue to 42° C in vitro raised heat shock protein-70, which is known to be tissue protective, and caused changes in alkaline phosphatase and gap junction proteins that were reversed to normalcy a few hours later.⁷ By contrast, in another study, heat applied in deep cavity preparations (prepared atraumatically in human teeth) caused histologic changes that were dependent on the proximity of the heat source to the pulp.¹⁶⁸ It was common in that study to see loss of odontoblasts or their aspiration into the dentinal tubules. In cases where the cavity floor was less than 0.5 mm from the pulp, areas of coagulation necrosis could be seen, although the patients remained asymptomatic for the 1-month duration of the study. The measurement of heat in the tooth being prepared, in areas other than the site of tooth preparation, occasionally shows reduction in temperature,⁸⁰ presumably because of the poor conductive properties of dentin and the cooling effect of compressed air from the high-speed handpiece. Furthermore, cavity and crown preparations include a number of other irritating stimuli, such as desiccation, severance of odontoblastic processes, vibration, and smearing of bacterial irritants onto the surface of dentin. Taken together, these findings suggest that the transient increase in temperature to levels relevant to modern dental procedures on its own may not be the culprit in inducing pulpal changes. Rather, the synergistic application of excessive heat with other irritation factors and its proximity to the pulp may induce pathologic changes.

FIG. 13-14 With adequate water and air spray coolant, the same cutting tools, and a comparable remaining dentin thickness, the intensity of the pulpal response with high-speed techniques (i.e., decreasing force) is considerably less traumatic than with lower-speed techniques (i.e., increasing force).

(From Stanley HR, Swerdlow H: An approach to biologic variation in human pulpal studies. J Prosthet Dent 14:365, 1964.)

FIG. 13-15 Without adequate water coolant, larger cutting tools (e.g., No. 37 diamond point) create typical burn lesions within the pulp when the remaining dentin thickness becomes less than 1.5 mm.

(From Stanley HR, Swerdlow H: An approach to biologic variation in human pulpal studies. J Prosthet Dent 14:365, 1964.)

FIG. 13-16 Burn lesion with necrosis and expanding abscess formation in a 10-day specimen. Cavity preparation dry at 20,000 rpm, with remaining dentin thickness 0.23 mm.

(From Swerdlow H, Stanley HR Jr: Reaction of the human dental pulp to cavity preparation. I. Effect of water spray at 20,000 rpm. J Am Dent Assoc 56:317, 1958.)

Desiccation

Desiccation during cavity and crown preparation has long been known to cause aspiration of odontoblastic nuclei into dentinal tubules and pulpal inflammation.³⁰ One study showed that as little as 30 seconds of continuous air drying of class V cavities in human molars with uninflamed pulp caused significant displacement of odontoblastic nuclei, pulp inflammation, and even areas of necrosis related to the areas that were dried.⁵¹ However, another study showed that the effects of desiccation are transient, in that within 7 to 30 days there is autolysis of the aspirated cells and formation of reactionary dentin.³² The pulp in cases with aspirated odontoblasts, following desiccation for 1 minute, was not sensitive to clinical scraping with an explorer. The sensitivity was restored with rehydration of the cavities and was increased in other cases where pulp inflammation was induced by microbial contamination.¹³⁸ In this study, despite the lack of sensitivity in desiccated cavities, neural elements were seen histologically to be pushed into the tubules like the odontoblastic nuclei. The disruption of the odontoblastic layer and peripheral neural elements in the pulp with desiccation was also observed in a rat model using axonal transport of radioactive protein.³⁶

Biologic and Chemical Irritation

Dental caries is clearly an infectious disease in which microorganisms and their virulence determinants constantly irritate the pulp, even at the early stages long before pulp exposure.³³ However, despite the elimination of visible caries during cavity preparation, the cavity floor is undoubtedly left with some contamination by caries bacteria. Whereas the rubber dam should be used with any cavity preparation to prevent cavity contamination with salivary microorganisms, the use of water coolants allows the cavity to be contaminated with bacteria from water lines. Concerns about residual cavity contamination prompted some to use cavity disinfection with caustic chemicals. Chemicals such as hydrogen peroxide, sodium hypochlorite, or calcium hydroxide solutions have been proposed for this purpose, although they may exert a toxic effect.⁵⁰ An earlier study showed that the amounts of residual bacteria following adequate restoration are not significant.¹⁵¹ Once dentin is exposed, there is constant outward flow of dentinal fluid that minimizes the inward flow of any noxious agents.²⁵² This may aid in the reduction of irritation from residual microbial factors in dentinal tubules.

In contemporary practice, most chemical irritation during restorative procedures results from the application of etching agents, especially strong acids in the form of total dentin etch, particularly if capping of exposed pulp is performed.^81,179 Etching is performed to remove the smear layer, promote physical adhesion of bonding agents to dentin by forming resin tags in the dentinal tubules, and promote permeation of the newer unfilled resin primers into the unmineralized surface layer of collagen to form the so-called hybrid layer.

If the cavity is relatively superficial and is adequately sealed with a restorative resin, then etching of dentin is probably not detrimental to the pulp, because of the narrow diameter of dentinal tubules and their low density in peripheral dentin.²⁸ In fact, one study documented that histologic evidence of bacteria in human cavities restored with composite was significantly less if the cavity had been etched with phosphoric acid than if it were etched with 17% ethylenediamine tetra-acetic acid (EDTA) or not etched.¹⁵⁹ Pulpal inflammation in this study was not correlated with the etching treatments but with bacterial presence; in cases of etching with phosphoric acid, if bacteria were also present, severe pulpal inflammation and necrosis could be seen.

In recent years, self-etching formulations have become popular because they eliminate the separate etching step involved in total-etch procedures. Some have speculated that the bonding of self-etching systems may be poorer than total-etch systems because of the weaker acidity of the acidic primers of self-etching systems compared to total-etch systems.²⁸ However, studies have shown no significant differences between the two adhesive systems in long-term in vitro bond strength, postoperative sensitivity,¹⁸⁸ long-term in vivo degradation,¹²⁵ or long-term in vitro bond strength.⁹ One clinical study showed no differences between the two systems with respect to bacterial leakage and the inflammatory response in the pulp.¹⁶⁴ The most important variable that affected the pulp in this study was the amount of bacterial leakage with either system.

Other factors that may contribute to pulpal irritation during resin placement from chemical/biologic irritants include unpolymerized monomer and polymerization shrinkage. Higher concentrations of monomeric resin components were shown to exert an inhibitory effect on T-lymphocytes and spleen cells¹¹³ and monocytes/macrophages^{133,196,197,208} in vitro. These components may leach directly into the pulp in deep cavities and cause chemical irritation.⁹⁸ Shrinkage during polymerization of composites may induce internal stresses on dentin and create voids that allow microleakage. Shrinkage of resins is estimated to range from 0.6% to 1.4% and should be minimized during placement by incremental curing and possibly starting the restoration with flowable resins.²⁸

In summary, the available evidence indicates that chemicals involved in modern restorative procedures may irritate the pulp if placed directly on an exposure or if there is microbial leakage along the tooth/restoration interface.

Proximity of Restorative Procedures to Dental Pulp and Surface Area of Dentin Exposed

It has been known for several decades that as the carious lesion progresses towards the pulp, particularly when the remaining dentin thickness (RDT) is less than 0.5 mm, there is an increasingly severe pulpal reaction, with a greater likelihood of the pulp undergoing irreversible pathosis.²⁰¹ The diameter and density of dentinal tubules increase closer to the pulp (Fig. 13-17). Based on the dentinal tubule density at the dentin-enamel junction (DEJ) (about 65,000/mm²) and the pulp (about 15,000/mm²),^74,78 it was estimated that the area occupied by tubule lumina at the DEJ was 1% of the total surface area at the DEJ and 22% at the pulp.¹⁸³ Thus it is not surprising that several studies have shown that pulpal inflammation in response to restorative procedures increases with the reduction in RDT.^1,53,158 A recent study examined the differential effects on the rat pulp of the preparation method, remaining dentin thickness, coolant, drill speed, conditioning with EDTA, and filling materials.¹⁵⁷ Subsequent to the cavity preparations, a tooth slice was obtained and maintained ex vivo as an organ culture for up to 2 weeks. The results showed that the remaining dentin thickness was the most important factor on pulpal injury.

FIG. 13-17 Convergence of tubules toward the pulp. A, Periphery of the dentin. Most surface area is occupied by intertubular dentin (), with a few tubules surrounded by hypermineralized peritubular dentin (). B, Near the pulp, the increase in tubule diameter has occurred largely at the expense of the peritubular dentin. This substrate has a high protein content. As the remaining dentin is made thinner (from A-B), the permeability of the dentin increases because both diameter and density of dentinal tubules are increased.

(Bouillaguet S: Biological risks of resin-based materials to the dentin-pulp complex. Crit Rev Oral Biol Med 15:47–60, 2004.)

With the passage of time following cavity preparation, there is reduction in the permeability of RDT.¹⁸⁶ This may be due to rapid deposition of reactionary dentin, the migration of large proteins into the tubules, and/or the diminution of tubule diameter as dentin becomes more sclerotic. Using a primate model, one study showed that the basic rate of secondary dentin deposition is about 0.8 µm/day, and this rate increases to an average of 2.9 µm/day following restorative procedures. Interestingly, dentin deposition was more rapid next to shallow cavities than deep cavities in one study,²⁵⁴ but another study showed that total reactionary dentin deposited was thicker in deeper and wider cavities.¹⁵⁶

Clinically it has been observed that postoperative sensitivity is common with many restorative procedures. In one study, it was shown that following resin composite restorations on patients, postoperative sensitivity was related to the depth of the cavity but not to the presence or absence of liners or bases.²⁴⁴

In addition to the depth and/or width of a large cavity preparation, a crown preparation exposes more dentinal tubules to microbial or chemical irritation. During crown fabrication, there are added irritation factors, such as length of time of the preparation, impression techniques, and imperfect adaptation of temporary restorations, leading to microleakage during the temporization period. Because of the precise engineering requirements of some restorations, some providers may be inclined to reduce the coolant during crown preparation steps such as finalizing the finishing lines. However, crown preparations without coolants have been shown to dramatically reduce pulpal blood flow in an animal model (Fig. 13-18). There are few studies available on the effects of modern crown and bridge techniques on the pulp. However, some long-term outcome studies have documented that the incidence of pulp necrosis following crown placement ranges from 10% to 18%.^70,245 As noted earlier, a more recent paper of work done in the 1980s in Hong Kong showed these figures to be much larger in bridge retainers compared to single crowns, reaching a value of up to 54% in anterior teeth.⁴⁵

FIG. 13-18 Effects of crown preparation in dogs, with and without water and air spray (at 350,000 rpm) on pulpal blood flow. Tooth preparation without water and air spray caused substantial decrease in pulpal blood flow, whereas that with water and air spray caused insignificant changes in the flow.

Permeability of Dentin and Odontoblastic Layer Between Area Being Restored and Pulp

The permeability of dentin plays an important role in the ingress of potential irritants to the pulp. It is clear from research done in the last 3 decades that dentin is not uniformly permeable, and that permeability depends on factors such as the location within the same tooth, the age of the patient, and the presence of pathologic conditions such as dental caries. Fundamentally, the permeability of dentin depends on the collective sum of permeability of individual tubules at a particular site in the tooth. The tubular diameter increases from about 0.6 to 0.8 µm close to the DEJ to about 3 µm at the pulp.⁸⁶ Given that bacterial cells are about 0.5 to 1 µm in diameter, it is evident that in deep cavity preparations, particularly when total-etch procedures are employed, bacteria can migrate through the remaining dentin into the pulp.

With age, the width of peritubular dentin increases, causing reduction in tubular lumen or sclerosis. Caries causes demineralization in superficial dentin, which is associated with remineralization and the formation of caries crystals within the tubules of inner undemineralized dentin (Fig. 13-19). This causes a decrease in permeability in dentin subjacent to the carious lesion¹⁸⁴ and could be considered a protective mechanism, since it may delay the progress of the carious lesion.

FIG. 13-19 Transmission electron micrographs (TEM) of undemineralized specimens of resin-bonded caries-affected dentin. A, Stained TEM of undemineralized specimens following the application of the self-etch ABF system to caries-affected dentin. The hybrid layer (H, between arrows) was about 3 µm thick, and the underlying undemineralized dentin (U) was highly porous (arrowhead). The dentinal tubule was covered with a smear plug (SP) and was partially obliterated with large caries crystals (pointer). (A), filled adhesive. B, Stained section of the total etch Single Bond adhesive bonded to caries-affected dentin. A hybrid layer (H) between 15 and 19 µm thick could be seen, with a partially demineralized zone (open arrows) above the undemineralized caries affected dentin (U). (T), dentinal tubule. (C), composite. C, Higher magnification of the basal part of the unusually thick hybrid layer (H) shown in (A). Banded collagen fibrils (open arrow) were separated by unusually wide and porous interfibrillar spaces (open arrowheads). A partially demineralized zone (Pd) was present along the demineralization front. This zone was not seen in phosphoric-acid-etched sound dentin (B). (U), undemineralized caries-affected dentin.

(From Yoshiyama M, Tay FR, Doi J, et al: Bonding of self-etch and total-etch adhesives to carious dentin. J Dent Res 81:556, 2002.)

It has been reported that the odontoblastic cell layer itself may contribute to the reduction of permeability to large molecules such as bacterial proteins or toxins. Experiments were conducted in which large protein markers were allowed to permeate the odontoblastic layer in experimental animals before and after cavity preparation. It was shown that irritation from cavity preparation increased the odontoblastic permeability only at the site of the cavity preparation.^106,240 In addition to the physical barrier to permeability and the production of reactionary or reparative dentin, the odontoblastic layer may in fact contribute to the host response of the dental pulp by expressing important inflammatory mediators^136,178 or recognize bacteria through toll-like receptors.^27,59,67,112

Pulpal Reactions to Restorative Materials

The effects of restorative materials on the dental pulp have been investigated and seem to relate directly to the permeability of the associated dentin. The degree of dentin permeability, however, is often variable and is governed by several factors including age and caries status.²³⁰ As noted before with respect to restorative procedures and bacterial ingress, perhaps the most important variable in dentin permeability to restorative materials is the thickness of dentin between the floor of the cavity preparation and the pulp.¹

Unbound components of resin materials and preparative agents such as acid etchants can affect the subjacent pulp by inducing an inflammatory response.^77,195 The indirect effects of desiccation and/or demineralization of dentin, as well as direct effects of the material itself when in contact with pulpal tissue, mediate this inflammatory response. Studies have shown that certain cytotoxic components of resin monomers (e.g., triethylene glycol dimethacrylate and 2-hydroxyethyl methacrylate) readily penetrate dentin.⁷² Similarly, eugenol and components of Ledermix (triamcinolone and demeclocycline) have been shown to pass through dentin into the subjacent pulp.^97,99 In vivo data show that these chemicals have an effect on the pulp, but the effect seems to be short lived and, in the absence of bacteria, reversible.²¹

The mechanisms whereby restorative materials exert an injurious effect on the dental pulp are varied. Evidence exists that supports direct and, in some instances, prolonged cytotoxicity, stimulation of hypersensitivity reactions, or impairment of the host immune response to bacteria. Some of the components of resin restorations are released at cytotoxic levels after polymerization is completed, leading to chronic stimulation and a resultant prolonged inflammatory response.⁷¹ Furthermore, even subtoxic concentrations of certain agents are capable of eliciting allergic reactions in humans.⁹⁸ Primates hyperimmunized with BSA showed significant pulpal damage with repeated antigenic challenge in class V cavity preparations, suggesting a role for antigen-antibody complex–mediated hypersensitivity in tissue destruction.²⁴ In a separate study, exposure to dentin primers elicited a delayed-type hypersensitivity reaction in guinea pigs.¹¹⁵ These studies taken together present a compelling argument for immune-mediated pulpal tissue damage subsequent to exposure to restorative materials. Foreign body reactions have also been described in pulps containing extruded globules of resin material.^102,103 Histologic examination of such pulps shows macrophages and giant cells surrounding the resin particles. Lastly, resin monomers have been shown to decrease the activity of immunocompetent cells in a dose-dependent manner in in vitro functional assays.¹¹³ Although all of these effects are documented, their extent and therefore morbidity on the dental pulp is speculative and doubtless does not act solely to effect pulpal demise. As previously noted, most restorative materials are placed adjacent to pulps that are previously compromised by bacterial insult; disease, débridement, and restoration of the tooth have cumulative effects on the dental pulp.

Although pulpal irritation is largely considered to be a negative sequela, the irritant potential of certain restorative materials is central to their usefulness in restorative dentistry. Calcium hydroxide is one of the oldest and most widely used medicaments for stimulation of dentinal bridge formation subsequent to microscopic or gross pulpal exposure. The low-grade pulpal irritation that it induces is important for dentinal bridge formation in exposures.^55,207 The degree of inflammation is dependent on the preparation of calcium hydroxide used. Aqueous suspensions of calcium hydroxide applied to exposed pulps causes superficial necrosis of pulpal tissue followed by tissue displaying low-grade inflammation. Within 30 days, the tissue subjacent to the necrotic zone has reorganized and resumed normal architecture. Hard-setting calcium hydroxide preparations are effective in eliciting dentinal bridge formation with a much smaller to nonexistent necrotic zone.⁹² This is preferable in vital pulp therapies such as the Cvek pulpotomy, where maintenance of the maximum amount of vital pulp tissue is desirable, and the extent of pulpal inflammation is minimal⁵⁴ (Fig. 13-20). The irritation potential of calcium hydroxide across intact dentin is dependent on factors such as the remaining dentin thickness and permeability. Application of calcium hydroxide to intact dentin appears to induce sclerosis by promoting crystal precipitation within the tubules, accompanied by reductions in permeability.¹⁵³

FIG. 13-20 Calcium hydroxide produces an inflammatory response that stimulates dentinal bridge formation. The dentin bridge forms lower in the tooth with calcium hydroxide paste (A) versus hard-setting calcium hydroxide (B).

In addition to the direct chemical effects of restorative materials, there are indirect factors that contribute to pulpal irritation. The technique sensitivity of certain materials predisposes them to faulty bonds to tooth structure that can translate to dentin hypersensitivity, recurrent disease, and pulpal inflammation or necrosis. Much attention has been given to the interface created between resin-bonded materials and dentin. During the etching process, the more highly mineralized peritubular dentin is preferentially dissolved, leaving free collagen fibrils and opening lateral tubular branches.^82,152 Applied resin infiltrates the exposed collagen mesh, creating a layer 5 to 10 µm thick referred to as the hybrid layer.¹⁶¹ This layer, along with the resin permeating exposed tubules, forms the bond between the resin and dentin. If the preparation is too dry, the collagen fibrils collapse, and the resin cannot effectively permeate the mesh, which results in a defective bond. The optimal degree of hydration of the preparation surface can vary from material to material, so resin restoration placement is technique sensitive. This same principle is applicable to the practice of bonding fractured tooth fragments where the segment has become dehydrated while outside of the mouth. Current protocols recommend rehydration of the segment prior to bonding, thus increasing the mechanical and presumably the microbial seal.⁶⁹ This is particularly important with a complicated crown fracture where the pulpal protection by intact dentin is absent.

Some restorative materials rely on their medicinal properties as well as their ability to seal a cavity preparation. Materials containing zinc oxide and eugenol (ZOE) fall into this category. ZOE is used for a variety of purposes in dentistry, largely because of its anesthetic and antiseptic properties. It has been shown to block transmission of action potentials in nerve fibers and to suppress nerve excitability in the pulp when applied to deep excavations.²³⁸ In addition, ZOE has good adaptation to dentin and inhibits bacterial growth on cavity walls. These properties have made this a favored material for temporary fillings but not long-term restorations; ZOE temporaries have been shown to leak after only a few weeks in situ.²⁶³

Direct Pulp Capping with Mineral Trioxide Aggregate

Direct capping of pulp exposures is indicated in pulps that were previously healthy and exposed by trauma or dental restorative procedures.²²⁹ Although calcium hydroxide has historically been the preferred dressing agent on mechanically exposed pulps, the use of mineral trioxide aggregate (MTA) has recently been proposed, even on carious pulp exposures.^16,26 Prospective animal studies and human case reports have evaluated the ability of MTA to allow for the formation of a reparative dentin bridge and maintain continued pulp vitality.^66,73,121 Although the results are generally favorable, one concern is of tooth discoloration if the gray MTA formulation is used on anterior teeth.

In a recent investigation, white MTA was compared to gray MTA in the capping of direct mechanical pulp exposures created in dogs’ teeth.¹⁸² No significant differences were found in the healing response to either material. At 1 week, none of the capped pulps showed necrosis close to the exposure site, and odontoblast-like cells were observed at the periphery and under the calcified bridge. At 2 weeks, almost all of the specimens from both types of MTA showed complete calcified bridge formation just below the exposure site. In a recent clinical study, MTA was used as a pulp capping material for carious pulp exposures.²⁶ Forty patients aged 7 to 45 were diagnosed with reversible pulpitis and had caries removed using a caries-detection dye and sodium hypochlorite for hemostasis. The treatment was performed in two visits to allow the MTA to set up and to confirm pulp sensibility to pulp tests in the second visit. Success was determined radiographically, with subjective symptoms, pulp testing with cold, and continued root formation on immature teeth. Outcomes were measured over a period of up to 9 years postoperatively and showed an overall success of 97%, with all the teeth in the immature root group showing success. Within the parameters of these studies, it seems that white MTA is a suitable capping agent for pulp exposures of healthy or reversibly inflamed pulps. It must be emphasized, however, that not only must the pulp capping agent be biocompatible and hopefully stimulate the formation of reparative dentin, but the prevention of bacterial ingress by the placement of a well-sealed restoration must also be provided.

Use of Hemostatic Agents and Disinfectants on Direct Pulp Exposures

As noted before, the use of direct capping procedures in an attempt to maintain the vitality of an exposed dental pulp has been a controversial area of pulp biology. In particular, the impact of preoperative diagnosis and the effects of various dental medicaments and materials on the long-term prognosis of exposed pulps have been questioned.^{53,95,179,215,221} With regard to the former, it has generally been accepted that carious pulp exposures offer poor therapeutic opportunities for continued pulp vitality with direct capping techniques.^17,95 In the case of the latter, there is still debate as to whether the toxicity of medicaments and materials placed on vital pulp tissues determines outcome, or if their ability to seal the cavity from further bacterial ingress is of prime importance. It is likely a combination of the two, as was shown in the recent clinical trial with MTA mentioned before.²⁶ Another factor in the prognosis of direct pulp caps is the ability to control hemorrhage at the exposure site.²²¹ Given the difficulty in creating a bacteria-free operating environment during tooth preparation, the ideal hemostatic agent also would have the ability to kill bacteria.

A recent study compared the effects of two hemostatic/disinfectant agents on the healing of experimental pulp exposures created in human third molar teeth and capped with calcium hydroxide.²¹¹ Pulp exposures were made in 45 maxillary wisdom teeth scheduled for extraction for orthodontic reasons. Teeth were randomly assigned to receive hard-setting calcium hydroxide pulp caps after a 30-second surface treatment with one of three agents: 0.9% saline, 2% chlorhexidine, or 5.25% sodium hypochlorite. The teeth were restored with class I bonded resin restorations, extracted after 7, 30, or 90 days, and processed for routine histologic evaluation. Although the 7-day saline specimens showed slightly less inflammatory response, there were no statistically significant differences between the groups with respect to all dependent measures over the course of the study. Complete healing was seen in 88% of all specimens at 90 days.

The pulps in these teeth were previously uninjured, and the exposures were made in a clean environment. Therefore, it seems that a mechanical exposure of a healthy pulp created during cavity preparation could be disinfected with either 2% chlorhexidine or 5.25% sodium hypochlorite (full concentration is now 6.0%), capped with a hard-setting calcium hydroxide formulation, and expected to have a favorable prognosis for healing.

Pulpal Reactions to Laser Procedures

Numerous studies have been published on the effect of using lasers on enamel, dentin, and pulp (see also Chapter 8). Laser use on hard tissue has been a popular area of research because of the potential benefits of efficiency, reduced sensitivity, disinfection, and precision. There are several different types of laser technologies available that depend on the wavelength, active medium, emission mode, delivery system, power output, and duration of application. The main types available in dentistry today are shown in Fig. 13-21. The CO₂ laser is historically the oldest type used on soft tissues and thus has been the most studied. It has the longest wavelength (10,600 nm). It cannot be delivered in an optic fiber, thus must be used in a hollow-tubelike wave guide in continuous gated-pulse mode. This means that the operator does not feel a solid resistance when using this laser. Er:YAG, Nd:YAG, or Ho:YAG lasers all have an active medium of a solid crystal of yttrium-aluminum-garnet, which is impregnated in erbium, neodymium, or holmium, respectively. Er:YAG has a wavelength of 2940 nm, delivered using a solid optic fiber. It has a high affinity for water and hydroxyapatite, thus can be used for removal of caries and cutting dentin with coolant. It can also be used on soft tissue. Ho:YAG laser has a wavelength of 2120 nm and has high affinity to water but not to tooth structure, thus is used primarily for soft-tissue surgery. Nd:YAG laser is also delivered fibroptically, has a wavelength of 1064 nm, and has been used extensively in dentistry because it has high affinity for water and pigmented tissues and offers good hemostasis, thus is used extensively in surgery.⁴⁸ In addition, there are lasers with low power output, such as HeNe, or helium neon (632 nm), and GaAlAs, or gallium-aluminum-arsenide (diode; semiconductor) (720-904 nm) lasers, which have been used in laser Doppler flowmetry and in treating dentin hypersensitivity.¹¹⁹

FIG. 13-21 Currently available dental wavelengths on the electromagnetic spectrum. Note all of the wavelengths are nonionizing.

(From Coluzzi DJ: An overview of laser wavelengths used in dentistry. Dent Clin North Am 44:753, 2000.)

Lasers in the Prevention, Diagnosis, and Treatment of Caries

Laser irradiation of deep susceptible pits and fissures may reduce the incidence of dental caries. Once caries develops, some lasers may be effective in removing the carious lesion and sparing undemineralized dentin because of their differential absorption by water and hydroxyapatite. Furthermore, if caries exposes the pulp in young teeth, particularly those with immature apex, lasers may be able to effectively excise coronal infected pulp in pulpotomy because of their hemostatic and antibacterial properties. All these potential uses prompted a large number of investigations on the effectiveness of lasers in these applications.

Some clinicians have proposed using lasers to enhance adhesion of pit and fissure sealants, but this was shown to not add any advantage following acid etching—a necessity for adhesion.¹⁴³ Laser fluorescence is used by the DIAGNOdent and DIAGNOdent pen, which are laser devices that have been introduced for the diagnosis of noncavitated caries. Although these devices initially showed some promising results,¹⁴⁴ more recent work suggests that they are best used as adjunctive devices to radiography and visual examination.^6,49,126

Laser ablation of superficial carious lesions may be more conservative than bur preparation. A controlled clinical trial supported this tenet when free-running pulsed Nd:YAG laser was used to ablate superficial pit and fissure caries in third molars scheduled for extraction⁸⁸ (Fig. 13-22). In this study, there were no histologic differences in the pulp response between the two groups.

FIG. 13-22 A, Dental caries. B, Pulsed Nd:YAG ablation byproducts (160 mJ, 10 Hz). C, Debris removed with acid etch and polishing. Enamel surface was faceted for reflection spectroscopy.

(From Harris DM, White JM, Goodis H, et al: Selective ablation of surface enamel caries with a pulsed Nd:YAG dental laser. Lasers Surg Med 30:342, 2002.)

From the perspective of effects on the pulp, most laser applications employed in cutting or modifying cavities in dentin or acting directly on the pulp tissue are important. Earlier studies showed reduced permeability of dentin in vitro with a XeCl excimer laser (a laser with a relatively short wavelength of 308 nm in the ultraviolet range).²²⁰ The apparent fusion of tubules in superficial layers of dentin was shown to occur with CO₂, Nd:YAG, and Er:YAG lasers in vitro.²⁵⁵ The pulpal responses to Nd:YAG and CO₂ lasers were not favorable. It was shown that Nd:YAG and, to a lesser degree, CO₂ lasers may be associated with charring and significant inflammation in the pulp compared with Er:YAG laser^235,255 (Fig. 13-23). More recently it was reported that water cooling was as necessary for laser ablation as it is for high-speed bur preparations.⁴¹ Studies have shown that Er:YAG laser appears to induce similar responses in the pulp to those seen with high-speed bur preparations at the level of light microscopy analysis.^{65,231,232,255} However, the findings with electron microscopy were different. It was reported that whereas shallow cavities ablated in rat molars using Er:YAG lasers did not show changes from baseline using light microscopy, transmission electron microscopy (TEM) showed disruption and degeneration of pulpal peripheral nerve endings and of myelin sheath in the immediate postoperative period (Fig. 13-24).¹⁰¹ This may explain the reduced sensitivity that accompanies laser cavity preparations. Thus in summary, it does not appear that the use of lasers provides predictable advantages in cavity preparation compared with traditional methods at this time.

FIG. 13-23 A-B, Histopathologic picture of Nd:YAG laser specimen with an increasing power. There is a direct relationship between the degree of pathologic changes and the increasing power of the laser. In fact, 1.5 W and the greater power cause permanent damage to the pulp.

FIG. 13-24 A, Control; normal odontoblastic process (arrow) and a few nerve terminals (arrowheads) are seen in a dental tubule of rat upper first molar. B, Six hours after Er:YAG laser irradiation; disrupted cell membrane of a nerve terminal that contains some granular vesicles (arrow) and shrinkage of an odontoblastic process (arrowhead) are noted in dentinal tubules just under the ablated area. Asterisk indicates the irradiated side (transmission electron micrograph, ×13,700; bar = 1 µm).

(From Inoue H, Izumi T, Ishikawa H, Watanabe K: Short-term histomorphological effects of Er:YAG laser irradiation to rat coronal dentin-pulp complex. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 97:246, 2004.)

For pulpotomy procedures, such as in primary teeth, permanent teeth with immature apex, or pulps that are exposed due to fracture and treated promptly, the lasers (particularly CO₂ lasers) may be useful in achieving precise surgical excision of coronal pulp and immediate hemostasis. A controlled clinical study showed that CO₂ laser pulpotomy was comparable to traditional methods in experimental pulpotomies of primary teeth scheduled for extraction for orthodontic reasons.⁶³ However, an animal study in which CO₂ and Nd:YAG lasers were compared revealed poor response with both lasers compared with calcium hydroxide.¹¹⁴ A more recent animal study using Er:YAG laser showed that the results are dependent on the power settings, in that lower energy delivered with this laser produced favorable results.¹²⁰

Pulpal Reactions to Cavity Preparation Using Air Abrasion Techniques

Air abrasion is another modality that has been adopted for conservative, nonpainful cavity preparations. Aluminum oxide particles are forced in a rapid stream onto the tooth structure and simultaneously evacuated from the field. An earlier study evaluated the effects of air abrasion in class V preparations using two different particle sizes (25 and 50 µm) and two different forces (80 and 160 psi) on the dental pulp of dogs. The findings showed that histologically, higher pressures and smaller particles yielded significantly fewer pulpal effects than the high-speed treated teeth, whereas lower pressures and larger particles were not significantly different.¹³² Air abrasion cavity preparations were more recently shown to be equivalent to high-speed bur preparations in microleakage studies if both techniques are followed by acid etching.²⁵⁰ Because of the lack of tactile control, the use of air abrasion is limited to specific situations such as shallow caries or pediatric applications.

Pulpal Reactions to Vital Bleaching Techniques

Vital bleaching techniques employ the use of strong oxidizing agents, namely 10% carbamide peroxide and hydrogen peroxide, to bleach enamel of teeth with vital pulp. There have been concerns about the potential for pulpal irritation during these procedures because of the long duration that the chemicals are in contact with the teeth, particularly if dentin with open tubules or cracks are present. An earlier study identified the toxicity of these chemicals on cell cultures in vitro.⁸⁴ Histologic or histochemical analysis of the pulp following bleaching for up to 2 weeks showed minor inflammatory changes in the pulp of the bleached teeth that were reversible.^8,76 One clinical report documented that if 16% carbamide peroxide was used, gingival irritation was evident; however, no changes in pulp vitality or in symptoms were noted. Even in patients who develop posttreatment symptoms, these tend to be reversible and could be prevented by treating the teeth with fluorides and by correcting restorative pretreatment deficiencies.¹⁶³ Clinical symptoms are likely to be due to increases in neuropeptides in the pulp. A recent report showed that light- and laser-activated bleaching systems increase substance P expression in the pulp to significant levels.⁴² An earlier clinical trial showed that vital bleaching using 10% carbamide peroxide in a custom tray for 6 weeks was safe for the pulp health for up to 10 years post treatment, although the bleaching effectiveness may decline with time.²⁰³

Pulpal Reactions to Periodontal Procedures

In an intact nontraumatized tooth, the dental pulp maintains its healthy existence throughout life because it is insulated from microbial irritation in the oral cavity (see also Chapter 15). Periodontal disease causes attachment loss, which exposes the root surface to the oral cavity. Occasionally, pulpal inflammation secondary to severe periodontitis is observed.¹³¹ Some reports have described bacterial infiltration through dentinal tubules of exposed root surface, causing mild inflammatory changes in the pulp (Fig. 13-25).¹²⁹ However, in a case report of 25 teeth that were extracted in a patient with extensive periodontal disease, none of the pulp tissue had significant inflammatory changes.²³⁶ It is much more common for pulp necrosis or failed healing of periradicular lesions to present clinically with signs of periodontal disease than for periodontal disease to cause pulpal pathosis. Primary endodontic, secondary periodontal pathosis is particularly evident if a perforation occurs in the pulp chamber or coronal third of the root during endodontic treatment and is not promptly treated, as happens in cases of vertical root fractures or congenital tooth defects such as palatal groove defect. Thus it is more likely for microbial irritants to move outward from a necrotic pulp to cause periodontal breakdown than for them to move inward from a periodontal pocket to cause irreversible pathosis in the pulp. The reasons for this observation are not fully understood. However, if the assumption is that bacteria may migrate through patent dentinal tubules in these situations, as is shown in Fig. 13-25, then it may be that the outward dentinal fluid flow in teeth with vital pulp contributes to the resistance to ingress of bacteria in sufficient amounts to cause a clinically significant disease process. Once the pulp degenerates, dentinal fluid flow no longer exists. Thus microbial irritants from the pulp may promote pocket formation and periodontal bone loss,¹¹⁰ and the prognosis of endodontic and periodontal treatment may be related,¹¹¹ since the microbial factors may pass across dentin more readily.

FIG. 13-25 Mandibular first molar of 49-year-old female, no pain. Clinically caries free. Calculus, periodontal disease, and bone loss from two thirds to three fourths of root. A, Note narrowness of pulp chamber seen throughout all serial sections (×8.5). B, Bacterial plaque and adjacent dentinal tubules with bacteria (oblique arrows in A) (×400). C, Farthest penetration of bacteria in dentinal tubules (vertical arrow in A) (×400). D, Where dentinal tubules invaded by bacteria terminate in the pulp (horizontal arrow in A), a small but dense accumulation of lymphocytes and macrophages can be seen. a, Artifact, pulp tissue torn away from dentin during processing (×400).

(From Langeland K: Tissue response to dental caries. Endod Dent Traumatol 3:149–171, 1987.)

Periodontal scaling and root planing may result in removal of cementum and exposure of dentin to the oral cavity. Frequently this treatment results in dentin hypersensitivity, as discussed previously. In theory, periodontal disease and its treatment should be associated with increased incidence of pulpal pathosis. In an older study, investigators induced periodontal disease in a primate model (using ligatures) and compared the effects on the pulp of periodontal disease with or without scaling.²² In teeth with periodontal disease, mild chronic inflammatory changes were observed in 29% of the teeth and could be seen in areas of the pulp related to bone loss. One of 40 teeth developed pulp necrosis. In teeth that received scaling, a similar percentage of 32% developed the same mild inflammation, but none developed pulp necrosis. In a later clinical study,²³ 52 periodontitis patients who had 672 teeth with vital pulp were followed up and maintained every 3 to 6 months for 4 to 13 years (mean 8.7 years). Of those teeth, 255 were bridge abutments. The results showed a significantly higher chance of pulpal complications in teeth that were bridge abutments than teeth that were not abutments (15% versus 3%; P < 0.01). Considering that both types of teeth had similar degrees of periodontal disease, the authors concluded that prosthodontic treatment is associated with pulpal involvement more frequently than periodontal disease and its treatment. Another histologic analysis of 46 teeth with varying degrees of periodontal disease and coronal restorations reached a similar conclusion.⁵⁶ Furthermore, two comprehensive reviews of the topic concluded that although the potential exists for periodontal disease and its treatment to cause pulpal pathosis, particularly if large lateral or accessory canals are exposed, this occurrence is rare.^87,205

Mechanical Irritants: Orthodontic Movement

The most conspicuous pulpal change observed in response to orthodontic forces is hemodynamic. Both human and animal studies have confirmed that both lateral and intrusive forces result in an increase in pulpal blood flow.^127,165,172 Furthermore, blood flow alterations are not confined to the tooth in active movement. Observed increases in blood flow are seen in teeth adjacent to the focus of movement forces, implying that directed forces on one tooth could shunt blood to proximal vessels supplying other oral structures including teeth. If orthodontic forces are extreme, circulatory interruptions can occur and result in pulpal necrosis.³⁴

Biochemical, biologic, and histologic studies of the effects of orthodontic movement have confirmed that metabolic as well as inflammatory changes can result. The dental pulp tissue respiration rate is depressed after short-term application of orthodontic force.⁸³ Biochemical and molecular markers confirm that apoptosis and necrosis of pulpal cells is also increased subsequent to movement.¹⁸⁹ However, it was shown that the inflammatory mediators IL-1α and TNF-α show minor increase in the pulp during orthodontic movement, compared to the increase in periodontal tissues.²⁵ Histologic examination of pulps in teeth subjected to intrusive forces showed vascular congestion and dilatation as well as vacuolization of the odontoblastic layer.^224-226 Most if not all of these effects are due to circulatory changes, and the consensus is that they are transient, provided the movement forces are not excessive.¹²⁴ It was recently shown, however, that pulp necrosis of teeth that had suffered trauma prior to undergoing orthodontic treatment was significantly increased, compared to teeth that had either of these conditions alone—particularly in lateral incisors and when the traumatized tooth had pulp canal obliteration.^18,19

Pulpal Reactions to Orthodontic Surgery

It has been known for decades that osteotomies in the maxilla or mandible may cause disruption in the blood supply to teeth in the area of the surgery, with resultant inflammation and/or necrosis.^{15,122,162,187} Occasionally the teeth affected show postoperative manifestations common with traumatic injuries, such as pulp canal obliteration.²⁴⁷ Animal studies have shown that if a safe distance of 5 to 10 mm is maintained between the site of the surgery and the teeth, minimal disruption occurs.^58,260 Using laser Doppler flowmetry, a number of studies have documented actual reduction in PBF immediately following maxillary Le Fort I osteotomy,^175,198,206 particularly if segmental osteotomy is performed.⁶⁴ In most cases, the blood flow is regained within months of the surgery. Recently a modification of the Le Fort I osteotomy technique was described in which the Le Fort I sectioning was combined with a horseshoe palatal osteotomy to spare any disruption to the descending palatine artery.⁸⁵ An examination of PBF of maxillary teeth using laser Doppler flowmetry, as well as the responsiveness to electric pulp testing, showed significant differences between the two surgical techniques in the postoperative recovery values (Fig. 13-26). In cases where the surgery did not disrupt the palatine artery, the PBF in the anterior teeth consistently increased without disruption in the postoperative period.

FIG. 13-26 A, Postoperative change of the mean pulpal blood flow in the upper incisors of the two groups. Pre, Before the operation; d, day(s) after the operation; M, months after the operation; bars, SD; *, P < 0.05; **, P < 0.01. B, The postoperative change in the percentages of teeth (upper incisors) with positive pulpal sensibility in the two groups. Pre, Before the operation; d, day(s) after the operation; M, months after the operation; *, P < 0.05.

(From Harada K, Sato M, Omura K: Blood-flow and neurosensory changes in the maxillary dental pulp after differing Le Fort I osteotomies. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 97:12–17, 2004.)

It should also be noted that occasionally teeth are traumatized during endotracheal intubation for surgery that requires general anesthesia, when the surgery itself is not related to the jaws or teeth.²¹²

Biomechanical Irritation: Parafunctional Habits

Occlusal loading of teeth affects deformation to varying degrees.⁸⁶ Enamel is largely resistant to flexure, but the underlying dentin demonstrates considerable elastic and viscoelastic characteristics. As a result, defects in enamel secondary to cracks, decay, and/or restorative preparation allow cuspal flexure, with subsequent pulpal responses presumably due to dentinal fluid flow secondary to compression and microleakage.⁹³ The magnitude of the pulpal response is dictated by the degree and chronicity of dentinal deformation.

Multiple factors influence the degree of tooth deformation during occlusal loading. Investigators have noted that preparation geometry has a direct impact on cuspal flexure. The width of the occlusal isthmus relative to the faciolingual dimension of the tooth, as well as the ablation of marginal ridges, directly impact on the degree of cuspal flexure.^246,199,181 MOD preparations have been shown to effect a 50% reduction in cuspal stiffness and resistance to fracture. Physical properties of the restorative material can also play a part in cuspal flexure. Studies have shown that polymerization shrinkage of certain resin composites can induce an inward deflection of cusps, with resultant stresses on tooth structure.^248,249

Symptomology from cuspal flexure can result from two primary sources. It has been theorized that cuspal flexure results in dentin deformation, thus promoting dentinal fluid flow that activates nerve endings in the odontoblastic layer of the tooth. This is supported in part by an in vitro study that found that dentinal fluid flow could be induced by occlusal loading of restored teeth.⁹³ A second source of pulpal pain is bacterial microleakage created by a gap at the restoration/dentin interface that is repeatedly opened during cycles of occlusal loading. If repeated cuspal flexure gives rise to a crack, dentinal exposure to bacteria and their byproducts is even greater. It is likely that in vivo, both dentinal fluid flow and bacterial access to dentinal surfaces work together to produce inflammation that is often manifested by thermal and biting sensitivity for the patient. In the instance of parafunctional habits, this is often combined with concussive periodontal forces to the periodontium that induce acute periradicular periodontitis, mobility, and radiographic changes.

Dentinal cracks expose tubules unoccluded by a smear layer and therefore offer a direct portal to the subjacent pulp. When dentinal tubules are freely exposed, there is an outward flow of dentinal fluid driven by relatively high pulpal tissue pressures. Dentinal fluid is composed of proteins such as fibrinogen and serum albumin, which can coagulate and effectively block the tubule lumen, thereby limiting fluid egress and resultant dentin hypersensitivity. This phenomenon can occur within 2 days. As this serves as a short-term protective mechanism for the pulp, dentinal sclerosis and tertiary dentin formation ultimately can provide greater protection for the pulp and ablation of symptoms. Clinical interventions include the application of materials that occlude the tubules and extracoronal restorations to prevent the propagation of cracks.

Pulpal Reactions to Implant Placement and Function

Osseointegrated implants are now a common option for the replacement of missing teeth. The placement of implants requires multifaceted preoperative radiographic techniques, including intraoral, tomographic, cephalometric, and panoramic imaging.²⁴¹ This assures that implant placement fully rests in bone and does not compromise neighboring structures, including teeth. The lack of attention to (1) the three-dimensional anatomy of the site of implant placement and (2) the orientation of neighboring teeth may lead to the implant perforating the root and devitalizing the pulp.^145,228

It is usually recommended that implants not be placed directly at a site where a periradicular lesion, particularly one with signs of purulence, exists; microbial irritants may interfere with osseointegration.¹⁹⁴ However, recent data suggest that immediate implant placement in sites that have been adequately débrided is successful.³⁸

Case reports have also claimed that teeth with periradicular lesions may reduce the success of neighboring implants, even if adequate endodontic treatment is performed.²²⁷ To address this issue, a study was reported in which implants were placed to replace premolars in dogs, and periradicular lesions were then induced. Some were treated nonsurgically or with combined surgical and nonsurgical treatment.²¹⁰ The results showed that the presence of treated or untreated periradicular lesions did not affect the long-term osseointegration of implants that were already osseointegrated. Following adequate endodontic treatment, complete resolution of periapical lesions that also involve neighboring implants has been reported.^139,223 Furthermore, implants that are not mobile but have apical periimplant lesions have been successfully treated with local débridement and “implant-apex resection” procedures.¹³

Regenerative Potential of the Dental Pulp

Recent studies and case reports suggest that the dental pulp has great regenerative potential, particularly in the immature permanent tooth (see also Chapter 16).^14,105 This has been attributed to the store of stem cells resident in the dental papillae of developing teeth.²¹⁸ Mesenchymal stem cells (MSCs) have been found in a variety of tissues and have proven to be pluripotential. Stem cells from the apical papilla (SCAP) of immature teeth have likewise been identified and have been shown to develop into dentinogenic cells, given the proper stimulation.^96,218 The results of these studies, coupled with case reports of continued root development subsequent to apical periodontitis in young teeth, suggest the potential for bioroot engineering in the future.⁹⁶