Vital Pulp Therapy

Endodontic Topics 2002, 2, 24–34 Printed in Denmark. All rights reserved

Copyright C Blackwell Munksgaard ENDODONTIC TOPICS 2002 1601-1538

Treatment outcome of vital pulp treatment PREBEN HØRSTED-BINDSLEV & HENRIK LØVSCHALL

Introduction Vital pulp treatment of permanent teeth in adults includes, as outlined in this chapter, direct pulp capping partial pulpotomy and vital pulpectomy. In clinical practice the methods applied for evaluating the outcome of vital pulp therapy in permanent teeth and the criteria used to distinguish between success and failure have remained almost unchanged for many years. Except for a slight tenderness or pain of short duration during the first couple of weeks after treatment, absence of pain is taken as a sign of success. The preand postoperative radiographical changes are mostly minor in diagnosis and treatment of the vital pulp. A condensing apical periodontitis, widening of the periodontal ligament space and disintegration of the lamina dura may be present with the diagnosis chronic pulpitis or from time to time immediately after vital pulpectomy. Success of the pulp treatment is assumed if the periapical changes disappear. However, persistence of an increased bone density is in general not expounded as treatment failure. Following direct capping and partial pulpotomy, success also includes a positive response to electrical and/or thermal tests. The reliability and the reproducibility of the tests are mediocre. As an example, pain may be absent, despite inflammatory changes in the pulp tissue. However, by adding together information from the different sources, an operational basis for estimation of the outcome may be made. More precise methods to evaluate the pulpal condition are Laser Doppler flowmetry, pulse oximetry and dual wavelength spectrophometry which all are based on monitoring of the vascular integrity of the pulp. But these methods are

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still, although not totally new, at a certain experimental level and not for use in general practice. The most precise evaluation ought to be the histologic examination of the tissue. For obvious reasons, this can only be done in experimental studies. But also, in such studies, the reproducibility and criteria are open for discu discussion ssion and misi misinterpr nterpretatio etation, n, as was already been documented in the classical study by Langeland almost 50 years ago, where he discussed the risk of misdiagnosis of artefacts (1).

Treatment of exposures The modern treatment regimen for direct pulp capping, partial pulpotomy and pulpectomy is most often based on information from clinical and radiographical studies and, to a lesser extent, on histological studies. The strength of controlled longitudinal, clinical and radiographical studies is that a great number of treatments can be evaluated over a considerable period of time. Histological studies which may disclose the true results of the treatments, the so-called usage tests, are relatively few compared with the clinical and radiographical studies. There are several reasons for this. Usage tests are costly, and most often performed in animals. Use of animals may arouse strong feelings in the population and it is generally desirable to minimize the use of animals for research. Usage tests in humans are, for various reasons, difficult to perform; first and foremost for ethical reasons but also because today only few teeth are available for this purpose. Less teeth are extracted for orthodon orthodontic tic reasons, and roots remain in the jaws, even in patients scheduled for immediate full dentures. As a consequence, most human histologic studies, especially on pulpectomy,

Treatment outcome of vital pulp treatment

date back 25–60years. The weakness of usage tests is that the number of teeth in the groups are few and, in addition, teeth may be lost during the histologic processes. This may cause problems of establishing statistically significant results. Thus, when outcome of vital pulp therapy is considered, we have, by and large, to rely on information from clinical and radiographical examinations, knowing that these may not tell the full story. Often inflammatory reactions in the coronal or apical pulp may prevail following treatment, despite absence of clinical or radiographical signs of pathosis. This fact is important to bear in mind when treatment is selected, prognosis discussed and result of treatment evaluated.

Mechanisms in wound healing of pulpal tissue Vital pulp tissue responds to manipulation in several ways. Exposure or surgical removal of the upper pulp tissue is a procedure which, even under the best circumstances, will result in a transient inflammation. Exposure of the dental pulp as a result of caries or tooth fracture is a clinical reality that requires optimal treatment. Experimental evidence suggests that skills, wound level, choice of instrumentation, choice of wound dressing, and asepsis, play important roles in the development of the initial surgical inflammation. The potential for healing by formation of a dentin bridge is good, provided that the pulp is not inflamed (2). The events taking place after wounding can be di vided into the phases of hemostasis, inflammation, proliferation, and remodeling. Wound healing is, however, a continuous process where the beginning and the end of each phase cannot be clearly determined and phases overlap (3). The observed sequence of initial pulp reactions is that which is expected when connective tissue is wounded. Failure to resolve inflammation after wounding leads to chronic nonhealing wounds (4), and pulp tissue responds similarly with absence of hard tissue healing. Initially, the tissue adjacent to the exposure is characterized by varying amounts of necrotic tissue, inflammatory cells, and extravasated erythrocytes. The initial injury triggers exudation of fibrinogen and blood coagulation and an acute response dominated by neutrophil granulocytes. Both particles from the

capping material and dentin chips are displaced into the underlying pulp tissue (5).

Inflammation Both trauma and bacterial infection stimulate release of pro-inflammatory cytokines in connective tissue. Vascular alterations and inflammatory cell infiltration are activated in order to eliminate the irritating molecules. Adhesion molecule interactions between blood leukocytes and endothelium enables transmigration from inside to outside the vessel wall in reponse to chemotactic signals (6). Bacterial components, such as endotoxin and other cell wall components, are implicated as pathogens in the development of pulpal inflammation (7). The host responds to antigens with production of antibodies and a cell-mediated immune response. The antibody response involves the production of immunoglobins circulating in the body that bind specifically to the foreign antigen that induced them. The cell-mediated immune response involves production of specialized cells that react with the foreign antigens on the surface of other host cells, e.g. in the lymph nodes (8). The unspecific defense-mechanism against bacteria and invading organisms releases enzymes and toxic metabolites. The complement system is a multifactorial protein cascade system and its major function is activation of cellular defense mechanisms, opsonisation of foreign particles for phagocytosis and the destruction of target cells. Released toxic metabolites leads to generation of highly active species eg oxygen radicals, halogen and hypochlorous which may also damage the cells of the host. Generation of reactive species from accumulated granulocytes and macrophages during the inflammatory phase is a critical event in successful host defense (9). The wound healing of pulp tissue has primarily been studied in relation to application of calcium hydroxide. Therefore the following discussion of cellular responses in wound healing will be based on reactions to calcium hydroxide.

Calcium hydroxide Calcium hydroxide-containing agents which were used at first by Hermann in 1930 have been widely used since (10–13). The effect of calcium hydroxide on exposed connective pulp tissue has thus for dec-

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Hørsted-Bindslev & Løvschall

ades been studied in experimental animals as well as in man (11, 14–18). Application of calcium hydroxide on exposed healthy pulp tissue results in release of hydroxide ions with a bactericidal effect, followed by a combination of lytic and coagulation necrosis in the wound surface. These necrotic layers repeatedly form what we interpret to be a biological membrane, beneath which the inflammatory and reparative processes occur. Probably as a result of the high pH of the calcium hydroxide (19), a bactericidal effect is obtained (20). Previous studies showed that pulp capping by using a variety of agents, e.g. with a high (21), low (22, 23) or neutral pH (15) may be followed by stimulation of dentin bridging. The beneficial effect of calcium hydroxide has been regarded as the result of a bactericidal effect and a chemical injury limited by a zone of necrosis, which caused slight irritation of the vital tissue and stimulated the pulp to defense and repair (24). Pulp capping using calcium hydroxide also induces apoptosis (25, 26) in the underlying pulp. Apoptosis is a non-inflammatory controlled, cell death mechanism, whereas necrosis induce a pro-inflammatory response (27, 28). The balance of their activity after pulp capping may therefore have crucial influence on the subsequent inflammatory response. A few hours after application of calcium hydroxide on pulpal tissue, inflammatory cells migrate towards the necrotic tissue, and the inflammatory infiltration lasts for a few days (29). Efforts have been made to find a formula which minimizes the pro-inflammatory actions, and at the same time stimulates dentin bridge formation (29–31).

Reparative dentinogenesis Yamamura (32) summarized the tissue reactions to pulp capping with calcium hydroxide in dog teeth as four stages: the exudative stage (1–5days), the proliferative stage (3–7 days), osteodentin formative stage (5–14days), and the tubular dentin formative stage (14 days and more) Fibrin exudation takes place under the capping material in the pulp tissue for up to 4days (33). After approximately 3–6 days, the inflammatory infiltration is replaced by a migration of granulation tissue originating from central pulp sites. The granulation tissue is arranged along the wound surface and consists primarily of newly-formed fibroblasts and capillary

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blood vessels which proliferate and grow into the damaged tissue. Layers of fibroblasts increase in thickness around the lesion. Synthesis of new collagen fibers along the tissue necrosis is detected from 4 days after application of pure calcium hydroxide. Cells surrounded by new matrix, including calcifying nodules, are found after 7days (16). The initial precipitation of minerals is associated with detection of matrix vesicles, indicating close similarity to mineralization in bone (34). The minerals are found to originate from the blood supply (35). After 11days, the new matrix is associated with cuboidal cells, and some cells with odontoblast-like differentiation. After 14 days, a clear odontoblast-like arrangement is observed (36). After 1 month, dentin bridges can be seen around the trauma, representing a defensive interface between the necrotic zone and the new odontoblast layer (37). Microscopic evaluation, however, revealed 89% of all dentin bridges contained tunnel defects (38). Secretion of matrix from a new generation of cells implies a discontinuity in tubular structure with subsequent reduction in dentin permeability. The nonspecific response leads to deposition of atubular dentinal matrix covered by cuboidal or polygonal preodontoblast-like cells, and inclusions of osteocyte-like cells are observed in a dense mineralizing matrix called osteodentin. Deep to the pulp injury, surviving postmitotic odontoblasts respond with deposition of reactionary dentin along the dentin walls. In such situations we observe a reactionary dentin matrix with less tubular density than in the primary dentin. Reparative dentinogenesis represents a complex sequence of biological processes. Series of wound healing reactions occur in the pulp tissue simultaneously, including vascular and cellular inflammatory reactions and recruitment of competent cells. Interactions of pulp cells with cytokines and extracellular matrix components during the complex cascade of wound healing reactions influence the dentinogenic potential of the pulp (39).

Stem cells During dental tissue repair, many of the tooth developmental processes are mimicked, leading to focal deposition of reactionary and reparative dentin at injury sites. The nature and specificity of these responses are determined in part by the extent of tissue injury (40). Studies on tooth epithelial–mesenchymal signaling in-


teractions have greatly increased our understanding of molecules that regulate dentinogenic events during tooth development (41). Expression of the odontoblast phenotype is characterized by a sequence of cytological and functional changes which occur at each site in the pulp chamber according to a specific pattern (42–44). It has been widely recognized that several forms of reparative mineralized tissues are synthesized by hard tissue-forming pulpal cells which differentiate outside the specific temporo-spatial pattern of tooth development in the absence of dental epithelium and its basement membrane. Different phenotypic characteristics have been described for odontoblast-like cells arising from various in vitro and in vivo experimental or clinical situations (39). The plethora of confusing terms used to describe physiological and pathological dentin, secreted after primary dentin formation, has led to a redefinition of ‘tertiary dentin’, which is subdivided into reactionary and reparative dentin (45). The healing of pulpo-dentinal defects requires both mobilization of connective tissue and differentiation of a new generation of odontoblast-like cells. Fitzgerald et al. (46) studied migration and proliferation in experimental pulp exposures in monkey teeth after pulp capping with calcium hydroxide dressing. Continuous influx of newly differentiating odontoblastlike cells originating from the deeper pulp was observed at the material–pulp interface. At least two replications of DNA are required after pulp capping before cell migration and expression of the new phenotype (46). Within the stromal pulp, e.g. the cell-rich subodontoblast layer, undifferentiated mesenchymal cells could provide the precursor cells. However, perivascular cells and other cell populations, including bone marrow stem cells migrating via the bloodstream, have also been proposed as progenitor cells. Nevertheless, it remains open whether odontoblast-like cells during pulpal repair derive from the original ectomesenchymal dental papilla cell population, which resides at older stages as undifferentiated or fibroblastlike cells, or from both ecto-mesenchymal and nondental cells (39). Whether progenitor cells giving rise to new odontoblast-like cells for reparative dentinogenesis are recruited via the pulpal perivascular area, from the pulp stroma, or from the subodontoblast layer remains to be elucidated. Further characterization of these cell populations and their developmental

history may elucidate not only the origin, but may also help to understand their specific behavior during reparative dentinogenesis.

Growth factors Tissue injury leads to alterations in gene expression and release of a range of cytokines including growth factors. Cytokines play a determinant role in regulation of cell proliferation, migration and differentiation during pulp healing. In particular, members of the transforming growth factor beta (TGF-b) family have been implicated in reparative dentinogenesis (47–49). Nearly half of the TGFb-1 in dentin matrix has been reported to be present in active form (50). However, TGF-b activity decreases with a short halflife (2–3min) (51) due to binding of active TGF-b to extracellular matrix, including, for example, shedded extracellular betaglycan-residues which bind to TGFb receptors (52). Recent progress in understanding molecular and cellular changes during tooth development, and how they are mimicked during dental tissue repair, offers the opportunity to assess whether this knowledge can be exploited to design new treatment strategies in vital pulp therapy. Stimulation of odontoblast differentiation has also been observed after basic fibroblast growth factor (bFGF) and TGFb-1 implantation (39), and after insulin-like growth factor I (IGF-I) implantation enhanced reparative dentinogenesis was observed (53). Specific molecules appear to be markers of a dentinogenic response (54). Several studies have shown that growth factor rBMP-7 implantation markedly stimulates reparative dentin (47, 48, 55) but fails in inflamed pulps with pulpitis (56). The mechanism whereby foregoing inflammation may inhibit dentin bridging (57, 58) remains to be elucidated. Application of exogenous signaling molecules offers opportunities for development of new therapies (40, 53), although a number of delivery considerations must be addressed before these can be introduced into clinical practice (40).

Direct capping and partial pulpotomy As shown above, the pulp tissue is able to respond positively to external noxious agents. In particular, animal studies have shown hard tissue formation

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without persistent inflammation under exposures following proper treatment (Table 1), whereas human studies have documented that absence of pain is not synonymous with success of treatment (59, 60). Clinical and radiographical studies from the last few decades have shown absence of pain, positive reactions to electric and thermal stimulation and normal periapical tissue following direct pulp capping in 80–95% of teeth that, preoperatively, did not show signs of irre versible pulpitis (61–63). Discussion has been raised as to the result of direct pulp capping following pulp exposure through carious dentin. When carious demineralization of the dentin has reached the pulp, usually severe inflammatory changes are present in relation to the affected dentinal tubules. About 95% success after direct capping and partial or total pulpotomy of carious molars in adolescents has been reported, even in cases with periapical changes (64–67). The theory has been that by doing partial or total pulpotomy, the most superficial part of the pulp, which may be characterized by inflammatory changes and bacterial infiltration, are removed and therefore the surgical wound would be situated in sound and reactive connective tissue. In a retrospective study, Hörsted et al. (63) showed no statistical significant difference in clinical success between cappings made following small exposures due to trauma from cavity preparation or perforation due to excavation of carious dentin in teeth without preoperative pain. In the study, a survival rate of 97% after 1year was reduced to 82% after 5years. The authors hypothesize that this reduction may be a consequence of subsequent operative procedures, such as replacement of fillings and/or new carious

Table1. Criteria of success versus failure of vital pulp treatment

Clinical criteria: O Absence or presence of pain – spontaneous, provoked, duration, dull or sharp O Sensitivity – positive or negative reaction to electric or thermal stimulation (direct capping and pulpotomy) O Percussion test – positive or negative Radiographical criteria: O Changes in appearance of the apical periodontium eg. widening of the periodontal ligament, changes in trabecular pattern, disintegration of lamina dura

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lesions. Furthermore, at the time of study, only acid etching was performed and no dentin bonding agent was used. This may have influenced the marginal leakage of some composite restorations, increasing the risk of failures due to bacterial infection of the dentin bridge, which is most often characterized by connective tissue inclusions and channels. The role of bacteria for the prognosis has been documented in several clinical and animal studies (57, 60, 62, 68). A higher success rate from capping the teeth of young individuals with a highly reactive pulpal tissue is expected to be higher compared to capping of pulp tissue from older patients where the pulp tissue is rich in fibers but poor in cells and vessels. Some studies have supported this view point (63, 64), although others have failed to show a negative correlation between age of the pulp and success rate (61, 62, 69).

Capping material Calcium hydroxide or calcium hydroxide compounds have, for many years, been the material of choice. But calcium hydroxide and most calcium hydroxide cements are liable to dissolution and, in cases of microleakage around restorations, bacteria may gain access to the exposure site. Therefore, much research has been devoted to generate alternative materials. However, the effect of calcium hydroxide has been verified in numerous histological and clinical studies and each time a new material for capping or pulpotomy is suggested, the effect of the new material is compared with the effect of calcium hydroxide (e.g. 70, 71). Recently, materials as hydroxyapatite, tricalcium phosphate, mineral trioxide aggregate (MTA), osteogenic protein (see BMP-7 above) and dentin bonding materials are being discussed. Studies on hydroxyapatite have shown very irregular and incomplete hard tissue formation (72, 73) and that tricalcium phosphate to be most active when used in combination with calcium hydroxide (74). The composition of MTA is very similar to Portland cement and, as such, the material sets hard in moist environments. During the setting reaction, calcium hydroxide is released and a high alkalinity is present in the exposed area. Histological studies in animals have shown high sealing ability and hard tissue inducing capacity (71, 75–78). The material has been recommended for repair of root perforations, as a root end filling material, for root-end-closure of permanent teeth and for direct


capping and pulpotomy but, although promising, the documentation from use in humans is primarily based on case studies (79, 80). At present, however, MTA seems to be promising candidate as an alternative to calcium hydroxide. Hard tissue formation after treatment with dentin bonding materials has also been shown in animal studies (81–83). The theory behind the use of dentin bonding materials for direct capping has been that the most important factor for healing is prevention of bacterial contamination of the pulpal tissue. If this can be achieved by sealing of the exposure site, organization of the injured tissue will start and odontoblast-like cells differentiate. Clinical and radiographical studies in humans have shown positive responses to vitality testing and absence of pain following direct capping with dentin bonding materials (70, 84–86), whereas histological results from animal studies have been inconclusive. Some have shown excellent results comparable with use of calcium hydroxide, whereas others have failed to show the same quality of tissue reactions as when calcium hydroxide is used (81, 82, 87–91). Despite the use of adhesives, bacteria have been found in the pulp, which has been attributed to problems of controlling hemorrhage and other operative difficulties. It is remarkable that the histological studies in humans have shown less success with dentin bond capping than after capping with calcium hydroxide (70, 84–86). It can be speculated whether a difference in species may be of significance in this respect. In conclusion: Pulp capping and partial pulpotomy with calcium hydroxide compounds are realistic treatment alternatives in properly selected cases compared to the more radical pulpectomy. Performed on teeth which are without clinical and radiographical signs of pulpitis and using a gentle operative technique without an interfering blood clot between the capping material and the pulp and without introducing infected dentin chips and capping material into the pulp, a high clinical success rate can be expected. In the long run, prevention of bacterial leakage may be of decisive importance. The cost of direct capping is also less compared with the alternatives in both time and money. It has thus been suggested that with selection of a pulp capping strategy, instead of a more radical treatment, the cost savings per year may amount to 29 million dollars in the United States (92).

Pulpectomy It is generally accepted that a story of spontaneous or long lasting provoked pain indicates irreversible and extended inflammatory changes of the pulp tissue and a more radical treatment has to be performed. In etiological terms, it is likely that the pulpal infection has reached a level where its elimination is not possible without removal of all of the pulp tissue. Vital pulpectomy gained general acceptance as the method of choice compared to the previously most often preferred mortal pulpectomy, following several studies published in the period from about 1940–70 (93–100). Mortal pulpectomy was abandoned for several reasons. First, the vital treatment is considered more biologically acceptable as it is difficult to control the spread of the mummifying medicaments which from time to time lead to serious pain and loss of supporting bone. Second, vital pulpectomy can be performed in one sitting, thereby reducing discomfort for the patient. With vital pulpectomy, the clinical aim is removal of the entire pulpal tissue short of the anatomical apex followed by a bacteria-tight, biocompatible and stable root filling. With this treatment, diseased, infected and often also non-infected and non-inflamed tissue is removed to an apical level where the wound surface can be kept to a minimum, the residual pulp tissue is well vascularized, and the conditions for healing are optimal, provided the entire treatment can be carried out under aseptic conditions. The tissue reactions immediately following extirpation and root filling show inflammatory reactions in the residual pulp with resorption of the canal walls. After a couple of months, apposition of hard tissue onto the resorption lines and only few inflammatory cells can be seen close to the root filling in successful cases. In vital cases with pulpitis the apical part of the pulp tissue is normally devoid of bacteria, but deviation from an aseptic procedure during endodontic treatment may introduce bacteria in the canal, which can jeopardize the treatment, causing an infection of the periapical tissue. Studies have provided strong indications that inappropriate asepsis during treatment of vital pulps may cause periapical inflammatory reactions (101, 102). Another factor of importance for the successful outcome of pulpectomy seems to be the distance from the anatomical apex to termination of the root filling.

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Fig.1. Capping of healthy pulp tissue in a rat molar with a calcium hydroxide cement (Dycal) is here observed after 3 days. Necrotic layers form a biological membrane beneath which the inflammatory and reparative processes occur. Next to the calcium hydroxide a layer of compression necrosis (arrow) and lytic necrosis (LN) are observed with a distinct border towards the underlying layer of coagulation necrosis (CN), which contains numerous dark pyknotic nuclei.

Thus, studies have shown that a distance from radiographical apex to root filling exceeding 3 mm reduces the success rate compared to a termination of the filling 0–3mm from the radiographical apex (95, 103, 104). Theoretically, a placement of the wound at the so-called apical constriction is aimed at (105). However, nature is not always in accordance with theory and where this place is impossible to define by touch, a distance of extirpation of 1–2mm from the radiographical apex is generally accepted. However, it should be considered that the histological measures of the residual pulp are most often less than the radiograph suggests, and that chronic inflammatory changes may prevail in the residual pulp despite absence of clinical and radiographical symptoms (94, 96, 97, 100, 106) (Fig. 1). This emphasizes again the fact that our normally accepted clinical and radiographical criteria for evaluation may not reflect the true situation. Excess of root filling material forced into a radiographically uninflamed periapical tissue may also result in prolonged healing or persisting inflammation, probably due to a combination of foreign body reaction and material toxicity (94, 95, 106–109). The effect of quality of the root filling and of root filling materials on the result will be dealt with in greater detail elsewhere in this issue. It should be mentioned here, however, that con-

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Fig.2. Apoptosis, a programmed cell death mechanism for elimination of surplus or damaged cells, is observed here in the odontoblast layer in rat molar day 7 after capping. The apoptotic cells are characterized by condensation of chromatine as a result of DNA degradation and formation of apoptotic bodies (arrows). The programmed cell death plays an important role as part of the pathophysiological defence system.

Fig.3. Dentin bridge (BD) 80 days following direct capping of a monkey pulp with a calcium hydroxide cement. The vacuoles subjacent to the bridge are caused by processing problems. The empty spaces centrally in the pulp are blood vessels and a normal structure of the connective tissue can be seen without inflammatory reactions.

vincing evidence of an apical obturation with hard tissue following root filling with calcium hydroxide containing root canal sealers and cements has not been given. Some studies have shown more hard tissue modelling following root filling with calcium hydroxide cements or following packing of sterile


Fig.4. Left: Radiograph of central incisor 12 months after pulpectomy in a patient due for maxillary immediate full denture. There were no clinical symptoms and pathological periapical changes. Right: Decalcified section of the central incisor shown to the left. The tissue close to the root filling cement (C) is dominated by numerous inflammatory cells (IN) and resorption of the canal walls. Further apically few inflammatory cells and apposition of hard tissue can be seen (H) (106).

dentin chips compared to other materials but only in rare instances a total apical constriction with hard tissue been shown (110–113). One of the reasons might be that, even though a delicate piece of work has been done during performance of the pulpectomy, the gentle technique in wound treatment that can be done in the coronal part of the pulp is impossible to do in the apical darkness. In conclusion: In controlled clinical and radiographical studies, success after pulpectomy can be obtained in about 95% of the cases, which is almost the same success rate as seen following direct capping and partial pulpotomy. The results following pulpectomy and necrotic cases without rarefactions are almost the same, whereas results from root canal treatment of cases with diagnosed periapical infection are significantly poorer (104, 108, 114–116). This indicates

that the battle against bacteria can be difficult to win. Thus, the best endodontics may be no endodontics, as demonstrated by indirect capping. The second best is endodontics where the healing potential of the pulp tissue is turned to the best advantage as in direct cappings/partial pulpotomy or if the pulpal wound can be situated in non-infected tissue as in pulpectomy.

References 1. Langeland K. Tissue changes in the dental pulp. An experimental histologic study. Oslo: Oslo University Press, 1957. 2. Mjør IA. Pulp-dentin biology in restorative dentistry. Part 7: The exposed pulp. Quintessence Int 2002: 33: 113–135. 3. Gottrup F, Andreasen JO. Wound healing subsequent to injury.In: Andreasen JO, Andreasen FM, eds. Textbook and color atlas of traumatic injuries to the teeth . Copenhagen: Munksgaard, 1994: 13–76.

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Hørsted-Bindslev & Løvschall 4. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med 1999: 341 : 738–746. 5. Hørsted P, El Attar K, Langeland K. Capping of monkey pulps with Dycal and a Ca-eugenol cement. Oral Surg Oral Med Oral Pathol 1981: 52 : 531–553. 6. Albelda SM, Smith CW, Ward PA. Adhesion molecules and inflammatory injury. FASEB J 1994: 8 : 504–512. 7. Seltzer S, Farber PA. Microbiologic factors in endodontology. Oral Surg Oral Med Oral Pathol 1994: 78: 634–645. 8. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular biology of the cell , 4th edn. New York: Garland Publishing, Inc., 2002. 9. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine , 2nd edn. Oxford: Oxford University Press, 1989. 10. Glass RL, Zander HA. Pulp healing. J Dent Res 1949: 28: 97–107. 11. Chiego DJJ. An ultrastructural and autoradiographic analysis of primary and replacement odontoblasts following cavity preparation and wound healing in the rat molar. Proc Finn Dent Soc 1992: 88 : 243–256. 12. Foreman PC, Barnes IE. Review of calcium hydroxide. Int Endod J 1990: 23 : 283–297. 13. Hermann BW. Dentinobliteration der Wurzelkanale nach Behandlung mit Calcium. Zahnarztl Rundschau 1930: 2 : 887–899. 14. Negm MM, Combe EC, Grant AA. Reaction of the exposed pulps to new cements containing calcium hydroxide. Oral Surg Oral Med Oral Pathol 1981: 51 : 190–204. 15. Oguntebi BR, Heaven T, Clark AE, Pink FE. Quantitative assessment of dentin bridge formation following pulp-capping in miniature swine. J Endod 1995: 21 : 79–82. 16. Schrøder U, Granath LE. Early reaction of intact human teeth to calcium hydroxide following experimental pulpotomy and its significance to the development of hard tissue barrier. Odontol Revy 1971: 22 : 379–395. 17. Cox CF, Bergenholtz G. Healing sequence in capped inflamed dental pulps of Rhesus monkeys ( Macaca mulatta ). Int Endod J 1986: 19 : 113–120. 18. Fitzgerald M, Heys RJ. A clinical and histological evaluation of conservative pulpal therapy in human teeth. Oper Dent 1991: 16 : 101–112. 19. Hanks CT, Bergenholtz G, Kim JS. Protein synthesis in vitro, in the presence of Ca (OH)2-containing pulp-capping medicaments. J Oral Pathol 1983: 12 : 356–365. 20. Bergenholtz G, Reit C. Reactions of the dental pulp to microbial provocation of calcium hydroxide tr eated dentin. Scand J Dent Res 1980: 88 : 187–192. 21. Stanley HR. Pulp capping: conserving the dental pulp ª can it be done? Is it worth it? Oral Surg Oral Med Oral Pathol 1989: 68 : 628–639. 22. Sasaki T, Kawamata-Kido H. Providing an environment for reparative dentine induction in amputated rat molar pulp by high molecular-weight hyaluronic acid. Arch Oral Biol 1995: 40 : 209–219. 23. Yoshimine Y, Maeda K. Histologic evaluation of tetracalcium phosphate-based cement as a direct pulp-capping agent. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1995: 79 : 351–358. 24. Schrøder U. Effects of calcium hydroxide-containing pulpcapping agents on pulp cell migration, proliferation, and differentiation. J Dent Res 1985: 64 Spec No: 541–548.

32

25. Løvschall H et al. Four distinct types of cell death observed during pulp-capping. In preparation. 26. Goldberg M, Lasfargues JJ, Legrand JM. Clinical testing of dental materials – histological considerations. J Dent 1994: 22 Suppl 2: S25–S28. 27. Løvschall H, Fejerskov O, Josephsen Kasem M, Mosekilde L. Apoptosis: molecular aspects. Nord Med 1997: 112: 271–275. 28. Løvschall H, Mosekilde L. Apoptosis. cellular and clinical aspects. Nord Med 1997: 112 : 133–137. 29. Schroeder HE. Pathologie oraler Strukturen , 3rd edn. Basel: Karger, 1997. 30. McShane CJ, Stimson PG, Bugg JL, Jennings RE. Tissue reactions to Dycal. J Dent Child 1970: 37 : 466–474. 31. Watts A, Paterson RC. Bacterial contamination as a factor influencing the toxicity of materials to the exposed dental pulp. Oral Surg Oral Med Oral Pathol 1987b: 64: 466– 474. 32. Yamamura T. Differentiation of pulpal cells and inductive influences of various matrices with reference to pulpal wound healing. J Dent Res 1985: 64 Spec No: 530–540. 33. Fitzgerald M. Cellular mechanics of dentinal bridge repair using 3H-thymidine. J Dent Res 1979: 58 : 2198–2216. 34. Hayashi Y. Ultrastructure of initial calcification in wound healing following pulpotomy. J Oral Pathol 1982: 11: 174–180. 35. Pisanti S, Sciaky I. Origin of calcium in the repair wall after pulp exposure in the dog. J Dent Res 1964: 43 : 641. 36. Mjør IA, Dahl E, Cox CF. Healing of pulp exposures: an ultrastructural study. J Oral Pathol Med 1991: 20: 496– 501. 37. Baume LJ. The biology of pulp and dentine. A historic, terminologic- taxonomic, histologic-biochemical, embryonic and clinical survey. Monogr Oral Sci 1980: 8 : 1–220. 38. Cox CF, Subay RK, Ostro E, Suzuki S, Suzuki SH. Tunnel defects in dentin bridges: their formation following direct pulp capping. Oper Dent 1996: 21 : 4–11. 39. Tziafas D. Reparative dentinogenesis. Thesis. Thessaloniki: University Studio Press, 1997. 40. Tziafas D, Smith AJ, Lesot H. Designing new treatment strategies in vital pulp therapy. J Dent 2000: 28 : 77–92. 41. Jernvall J, Thesleff I. Reiterative signaling and patterning during mammalian tooth morphogenesis. Mech Dev 2000: 92: 19–29. 42. Jernvall J, Keranen SV, Thesleff I. From the cover: evolutionary modification of development in mammalian teeth: quantifying gene expression patterns and topography. Proc Natl Acad Sci USA 2000: 97 : 14444–14448. 43. Løvschall H, Fejerskov O, Josephsen K. Age-related and site-specific changes of pulp histology in Wistar rat molars. Arch Oral Biol 2002: 1197: 1–7. 44. Ruch JV. Odontoblast differentiation and the formation of the odontoblast layer. J Dent Res 1985: 64 Spec No: 489– 498. 45. Smith AJ, Cassidy N, Perry H, Begue Kirn C, Ruch JV, Lesot H. Reactionary dentinogenesis. Int J Dev Biol 1995: 39: 273–280. 46. Fitzgerald M, Chiego DJJ, Heys DR. Autoradiographic analysis of odontoblast replacement following pulp exposure in primate teeth. Arch Oral Biol 1990b: 35 : 707– 715.

Treatment outcome of vital pulp treatment 47. Nakashima M. Induction of dentin formation on canine amputated pulp by recombinant human bone morphogenetic proteins (BMP) -2 and -4. J Dent Res 1994: 73: 1515–1522. 48. Rutherford RB, Wahle J, Tucker M, Rueger D, Charette M. Induction of reparative dentine formation in monkeys by recombinant human osteogenic protein-1. Arch Oral Biol 1993: 38 : 571–576. 49. Rutherford RB, Spängberg L, Tucker M, Rueger D, Charette M. The time-course of the induction of reparative dentine formation in monkeys by recombinant human osteogenic protein-1. Arch Oral Biol 1994: 39 : 833–838. 50. Smith AJ, Matthews JB, Hall RC. Transforming growth factor-beta 1 (TGF-beta 1) in dentine matrix. Ligand acti vation and receptor expression. Eur J Oral Sci 1998: 106: 179–184. 51. Wakefield LM, Winokur TS, Hollands RS, Christopherson K, Levinson AD, Sport MB. Recombinant latent transforming growth factor beta 1 has a longer plasma half-life in rats than active transforming growth factor beta 1, and a different tissue distribution. J Clin Invest 1990: 86: 1976– 1984. 52. Shen Y, Shenk T. Relief of p53-mediated transcriptional repression by the adenovirus E1B 19-kDa protein or the cellular Bcl-2 protein. Proc Natl Acad Sci USA 1994: 91 : 8940–8944. 53. Lovschall H, Fejerskov O, Flyvbjerg A. Pulp-capping with recombinant human insulin-like growth factor I (rhIGF-I) in rat molars. Adv Dent Res 2001: 15 : 108–112. 54. Be´gue-Kirn C, Krebsbach PH, Bartlett JD, Butler WT. Dentin sialoprotein, dentin phosphoprotein, enamelysin and ameloblastin: tooth-specific molecules that are distinctively expressed during murine dental differentiation. Eur J Oral Sci 1998: 106 : 963–970. 55. Jepsen S, Albers HK, Fleiner B, Tucker M, Rueger D. Recombinant human osteogenic protein-1 induces dentin formation: an experimental study in miniature swine. J En- dod 1997: 23 : 378–382. 56. Rutherford RB. BMP-7 gene transfer to inflamed ferret dental pulps. Eur J Oral Sci 2001: 109 : 422–424. 57. Cox CF, Bergenholtz G, Heys DR, Syed SA, Fitzgerald M, Heys RJ. Pulp capping of dental pulp mechanically exposed to oral microflora: a 1–2 year observation of wound healing in the monkey. J Oral Pathol 1985: 14 : 156–168. 58. Watts A, Paterson RC. Pulp-capping studies with Analar calcium hydroxide and zinc oxide-eugenol. Int Endod J 1987: 20 : 169–176. 59. Nyborg H. Healing processes in the pulp on capping. Acta Odontol Scand 1955: 13 : 1–130. 60. Nyborg H. Capping of the pulp. Odontol Tidskr 1958: 66: 296–364. 61. Haskell EW, Stanley HR, Chellemi J, Stringfellow H. Direct pulp capping treatment: a long-term follow-up. J Am Dent Assoc 1978: 97 : 607–612. 62. Baume LJ, Holz J. Long term clinical assessment of direct pulp capping. Int Dent J 1981: 31 : 251–260. 63. Hørsted P, Søndergaard B, Thylstrup A, El Attar K, Fejerskov O. A retrospective study of direct pulp capping with calcium hydroxide compounds. Endod Dent Traumatol 1985: 1 : 29–34. 64. Zilberman U, Mass E, Sarnat H. Partial pulpotomy in carious permanent molars. Am J Dent 1989: 2 : 147–150.

65. Mejare I, Cvek M. Partial pulpotomy in young permanent teeth with deep carious lesions. Endod Dent Traumatol 1993: 9 : 238–242. 66. Caliskan MK. Pulpotomy of carious vital teeth with periapical involvement. Int Endod J 1995: 28 : 172–176. 67. Nosrat IV, Nosrat CA. Reparative hard tissue formation following calcium hydroxide application after partial pulpotomy in cariously exposed pulps of permanent teeth. Int Endod J 1998: 31 : 221–226. 68. Bergenholtz G. Evidence for bacterial causation of adverse pulpal responses in resin-based dental restorations. Crit Rev Oral Biol Med 2000: 11 : 467–480. 69. Heyduck G, Wegner H. Klinische, röntgenologiske und histologische Ergebnisse nach Vitalbehandlung der freigelegten Pulpa. Stomatol DDR 1978: 28 : 614–619. 70. Pereira JC, Segala AD, Costa CAS. Human pulpal response to direct pulp capping with an adhesive system. Am J Dent 2000: 13 : 139–147. 71. Faraco IM Jr, Holland R. Response of the pulp of dogs to capping with mineral trioxide aggregate or a calcium hydroxide cement. Dent Traumatol 2001: 17 : 163–166. 72. Jaber L, Mascras C, Donohue WB. Electron microscope characteristics of dentin repair after hydroxyapatite direct pulp capping in rats. J Oral Pathol Med 1991: 20: 502– 508.492. 73. Se´bay RK, Asci S. Human pulpal response to hydroxyapatite and a calcium hydroxide material as direct capping agents. Oral Surg 1993: 76 : 485–492. 74. Yoshiba K, Yoshiba N, Iwaku M. Histological observations of hard tissue barrier formation in amputated dental pulp capped with (-tricalcium phosphate containing calcium hydroxide. Endod Dent Traumatol 1994: 10 : 113–120. 75. Torabinejad M, Watson TF, Pitt Ford TR. Sealing ability of a mineral trioxide aggregate when used as a root end filling material. J Endod 1993: 19 : 591–595. 76. Holland R, de Souza V, Nery MJ, Faraco IM Jr, Bernab JFE, Otoboni Filho JA, Dezan E Jr. Reaction of rat connective tissue to implanted dentin tube filled with mineral trioxide aggregate, Portland Cement or calcium hydroxide. Braz Dent J 2001: 12 : 3–8. 77. Holland R, de Souza V, Nery MJ, Faraco IM Jr, Bernab JFE, Otoboni Filho JA, Dezan E Jr. Healing process of dog dental pulp after pulpotomy and pulp covering with mineral trioxide aggregate or Portland Cement. Braz Dent J 2001: 12 : 109–113. 78. Tziafas D, Pantelidou O, Alvanou A, Belibasakis G, Papadimitriou S. The dentinogenic effect of mineral trioxide aggregate (MTA) in short-term capping experiments. Int En- dod J 2002: 35 : 245–254. 79. Torabinejad M, Chivian N. Clinical applications of mineral trioxide aggregate. J Endod 1999: 25 : 197–205. 80. Shabahang S, Torabinejad M. Treatment of teeth with open apices using mineral trioxide aggregate. Pract Peri- odont Aesthet Dent 2000: 12 : 315–320. 81. Cox CF, Hafez AA, Akimoto N, Otsuki M, Suzuki S, Tarim B. Biocompatibility of primer, adhesive and resin composite systems on non-exposed and exposed pulps of non-human primates. Am J Dent 1998: 11 (special issue): 56–63. 82. Kitasako Y, Arakawa M, Sonoda H, Tagami J. Light and scanning electron microscopy of the inner surfaces of resins used in direct pulp capping. Am J Dent 1999: 12: 217– 221.

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Hørsted-Bindslev & Løvschall 83. Costa CAS, Mesas AN, Hebling J. Pulp response to direct capping with an adhesive sytesm. Am J Dent 2000: 13: 81–87. 84. Hebling J, Giro EMA, de Souza Costa CA. Biocompatibility of an adhesive system applied to exposed human dental pulp. J Endod 1999: 25 : 676–682. 85. Cehreli ZC, Turgut M, Olmez S, Dagdeviren A. Short term human primary pulpal response after direct pulp capping with fourth-generation dentin adhesives. J Clin Pedi- atr Dent 2000: 25 : 65–77. 86. de Souza Costa CA, Lopes do Nascimento AB, Teixeira HM, Fontana UF. Response of human pulps capped with a self-etching adhesive system. Dent Mat 2001: 17 : 230– 240. 87. Kitasako Y, Inokoshi S, Tagami J. Effects of direct resin pulp capping techniques on short-term response of mechanically exposed pulps. J Dent 1999: 27 : 257–263. 88. Pameijer CH, Stanley HR. The disastrous effects of the ‘Total Etch’ technique in vital pulp capping in primates. Am J Dent 1998: 11 (special issue): 45–54. 89. Tarim B, Hafez AA, Suzuki SH, Suzuki S, Cox CF. Biocompatibility of optibond and XR-bond adhesive systems in nonhuman primate teeth. Int J Periodont Rest Dent 1998: 18: 87–99. 90. Ölmez A, Öztas N, Basak F, Sabuncuoglu B. A histopathologic study of direct pulp-capping with adhesive resins. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998: 86: 98–103. 91. Corte´s O, Garcı´a C, Bernab A. Pulpal evaluation of two adhesive systems in rat teeth. J Clin Pediatr Dent 2000: 25: 73–77. 92. Maryniuk GA, Haywood VB. Placement of cast restorations over direct pulp capping procedures: a decision analytic approach. J Am Dent Assoc 1990: 120 : 183–187. 93. Nygaard Östby B. Über die Gewebsveranderungen im api- kalen Paradentium des Menschen nach versciedenartigen Eingriffen in den Wurzelkanülen. Eine klinische röntgenol- ogische und histo-patologische Studie , No. 4. Oslo: Skrifter utgitt av Det Norske Videnskaps-Akademi i Oslo, 1939: 1–223. 94. Ketterl W. Histologische Untersuchungen an vitalextirpierten Zähnen. Stoma 1963: 16 : 85–110. 95. Ketterl W. Kriterien für den Erfolg der Vitalextirpation. DDZ 1965: 20 : 407–416. 96. Nyborg H, Tullin B. Healing processes after vital extirpation. Odont Tidsskr 1965: 73 : 430–446. 97. Engstrøm B, Spängberg L. Wound healing after partial pulpectomy. A histologic study performed on contralateral tooth pairs. Odont Tidsskr 1967: 75 : 5–18. 98. Baume JL, Holz J, Risk LB. Radicular pulpotomy for category III pulps. Part II. Instrumentation and technique. J Prosthet Dent 1971: 25 : 525–531. 99. Baume JL, Holz J, Risk LB. Radicular pulpotomy of category III pulps. Part III. Histologic evaluation. J Prosthet Dent 1971: 26 : 649–657.

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100. Lambjerg-Hansen H. Vital and mortal pulpectomy on permanent human teeth. An experimental comparative histologic investigation. Scand J Dent Res 1974: 82 : 243–332. 101. Engstrøm B, Lundberg M. The correlation between positive culture and the prognosis of root canal therapy after pulpectomy. Odontol Revy 1965: 16 : 193–206. 102.Pitt Ford RG. Vital pulpectomy and unpredictable procedure. Int Endod J 1982: 15 : 121–126. 103.Grahne´n H, Hansson L. The prognosis of pulp and root canal therapy. A clinical and radiographic follow-up examination. Odont Revy 1961: 12 : 146–165. 104.Kerekes K, Tronstad L. Long-term results of endodontic treatment performed with a standardized technique. J En- dod 1979: 5 : 83–90. 105. Ricucci D. Apical limit of root-canal instrumentation and obturation, part 1. Literature review. Int Endod J 1998: 31: 384–393. 106.Hørsted P. Studies on the root filling cement Bi-Oxol. A clinical, roentgenological and histological investigation. Acta Odont Scand 1972: 30 : 187–199. 107. Seltzer S, Soltanoff W, Sinai I, Smith J. Biologic aspects of endodontics. IV. Periapical tissue reactions to root-filled teeth whose canals had been instrumented short of their apices. Oral Surg Oral Med Oral Pathol 1969: 28: 724– 738. 108. Halse A, Molven O. Overextended gutta-percha and Kloroperka N-root canal fillings. Radiographic findings after 10–17 years. Acta Odontol Scand 1987: 45 : 171–177. 109. Ricucci D, Langeland K. Apical limit of root-canal instrumentation and obturation, part 2. A histological study. Int Endod J 1998: 31 : 394–409. 110. Tronstad L. Tissue reactions following apical plugging of the root canal with dentin chips in monkey teeth subjected to pulpectomy. Oral Surg Oral Med Oral Pathol 1978: 45: 297–304. 111. Petersson K, Hasselgren G, Petersson A, Tronstad L. Clinical experience with the use of dentine chips in pulpectomies. Int Endod J 1982: 15 : 161–167. 112. Safavi K, Hørsted P, Pascon EA, Langeland K. Biological evaluation of the apical dentin chip plug. J Endod 1985: 11: 18–24. 113. Tronstad L, Barnett F, Flax M. Solubility and biocompatibility of calcium hydroxide-containing root canal sealers. Endod Dent Traumatol 1988: 4 : 152–159. 114.Molven O, Halse A. Success rates for gutta-percha and Kloroperka N- root fillings made by undergraduate students: radiographic findings after 10–17 years. Int Endod J 1988: 21 : 243–250. 115.Sjøgren U, Hägglund B, Sundqvist G, Wing K. Factors affecting the long-term results of endodontic treatment. J Endod 1990: 16 : 498–504. 116. Friedman S, Lost C, Zarrabian M, Trope M. Evaluation of success and failure after endodontic therapy using a glass ionomer cement sealer. J Endod 1995: 21 : 384–390.

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