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Human pulps capped with PDGF: A pilot study

September 22, 2016 / Categories: Digital Dentistry, Implant Dentistry

Pellegrini, Gaia

Dellavia, Claudia

Generali, Paolo

Allievi, Cristina

Re, Dino

Rasperini, Giulio

Growth factors have shown the potential to promote odontoblast-like cell di erentiation and induce the formation of reparative dentin. The aims of this pilot study were to develop a regenerative approach to pulp capping using platelet-derived growth factor (PDGF) BB and to describe histologically the pulp tissue response.

Introduction

The dental pulp provides nutrition and sensory properties to dentin and has reparative capacity to react to injury. When the injury results in odontoblast death, a new generation of odontoblast-like cells may di erentiate from progenitor cells within the pulp and secrete a reparative dentin matrix.1Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Robey PG, Shi S. Stem cell properties of human dental pulp stem cells.
→J Dent Res. 2002 Aug;81(8):531–35.

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Pulp capping is a common procedure that induces reparative dentin formation after pulp exposure due to cavity preparation, caries removal or trauma. Calcium hydroxide, zinc oxide eugenol cements, composite resins, mineral trioxide aggregate (MTA) and glass ionomer cements are used in clinical daily practice.2Zhu C, Ju B, Ni R. Clinical outcome of direct pulp capping with MTA or calcium hydroxide: a systematic review and meta analysis.
→Int J Clin Exp Med. 2015 Oct; 8(10):17055–60.
3Komabayashi T, Zhu Q, Eberhart R, Imai Y. Current status of direct pulpcapping materials for permanent teeth. →Dent Mater J. 2016;35(1):1–12. However, several concerns have been listed regarding the use of these materials for pulp capping, including cytotoxic effects,4Accorinte ML, Loguercio AD, Reis A, Costa CA. Response of human pulps capped with di erent self-etch adhesive systems.
→Clin Oral Investig. 2008 Jun;12(2):119–27.
the lack of adequate bleeding control after acid etching5Cox CF, Tarim B, Kopel H, Gurel G, Hafez A. Technique sensitivity: biological factors contributing to clinical success with various restorative materials.
→Adv Dent Res. 2001 Aug;15(1):85–90.
and the new hard-tissue formation at the expense of pulp chamber width, causing narrowing of root canals.6Nakamura Y, Hammarström L, Matsumoto K, Lyngstadaas SP. The induction of reparative dentine by enamel proteins.
→Int Endod J. 2002 May;35(5):407–17.
Although calcium hydroxide is the most widely used pulp capping agent to encourage hard-tissue bridging, the material is not able to e ectively induce new tissue formation.7Olsson H, Petersson K, Rohlin M. Formation of a hard tissue barrier after pulp cappings in humans. A systematic review.
→Int Endod J. 2006 Jun;39(6):429–42.
Bridge formation remains unpredictable, with varying thickness and numerous tunnel defects,8Cox CF, Sübay RK, Ostro E, Suzuki S,
Suzuki SH. Tunnel defects in dentin bridges: their formation following direct pulp capping. →Oper Dent. 1996 Jan-Feb;21(1):4–11.
suggesting that it may be of insu icient quality to protect the pulp against bacterial microleakage along the restoration margins. Several articles have addressed the use of MTA for pulp capping and demonstrated a hard-tissue barrier beneath the MTA; however, pulpal soft tissue enclosed within the hard-tissue barrier and unpredictable dentin bridge formation were observed.9Nair PN, Duncan HF, Pitt Ford TR, Luder HU. Histological, ultrastructural and quantitative investigations on the response of healthy human pulps to experimental capping with mineral trioxide aggregate: a randomized controlled trial.
→Int Endod J. 2008 Feb;41(2):128–50.
10Roberts HW, Toth JM, Berzins DW, Charlton DG. Mineral trioxide aggregate material
use in endodontic treatment: a review of the literature.
→Dent Mater. 2008 Feb;24(2):149–64.

Recently, a growth factor delivery approach has been introduced to induce reparative dentin formation in noninflamed mechanically exposed pulps.11Nakashima M. Induction of dentin formation on canine amputated pulp by recombinant human bone morphogenetic proteins (BMP)-2 and -4.
→J Dent Res. 1994 Sep;73(9):1515–22.
12Dobie K, Smith G, Sloan AJ, Smith AJ. E ects of alginate hydrogels and TGF- 1 on human dental pulp repair in vitro.
→Connect Tissue Res. 2002;43(2-3):387–90.
Rutherford et al. examined histologically the reparative dentin formation of pulp treated with osteogenic protein-1 (bone morphogenetic protein [BMP] 7) in monkeys.13Rutherford 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 Jul;38(7):571–6.
They reported that BMP-7 has the potential to induce the formation of reparative dentin and related the amount of newly formed dentin to the amount of implanted protein. Nakashima observed histologically the induction of tubular dentin formation in teeth capped with BMP-2 and -4 in monkeys.11 An in vivo study has demonstrated with histomorphometric analysis the role of transforming growth factor in promoting odontoblast-like cell di erentiation and the secretion of extracellular matrix.14Zhang W, Walboomers XF, Jansen JA. The formation of tertiary dentin after pulp capping with a calcium phosphate cement, loaded with PLGA microparticles containing TGF-beta1.
→J Biomed Mater Res A. 2008 May;85(2):439–4.
The effects of enamel matrix protein on pulp capping have been evaluated histologically and immunohistochemically in animal13 and human studies.15Olsson H, Davies JR, Holst KE, Schröder U, Petersson K. Dental pulp capping: e ect of Emdogain Gel on experimentally exposed human pulps.
→Int Endod J. 2005 Mar;38(3):186–94.
16Sabbarini J, Mohamed A, Wahba N, El-Meligy O, Dean J. Comparison of enamel matrix derivative versus formocresol as pulpotomy agents in the primary dentition.
→J Endod. 2008 Mar;34(3):284–7.
After application of enamel matrix protein, the damaged pulp showed at first a reparative process with formation of a scar and moderate inflammatory infiltrate. Subsequently, neogenesis of normal dental pulp occurred and odontoblast-like cells produced reparative dentin.17Nakamura Y, Slaby I, Matsumoto K, Ritchie HH, Lyngstadaas SP. Immunohistochemical characterization of rapid dentin formation induced by enamel matrix derivative. →Calcif Tissue Int. 2004 Sep;75(3):243–52. In the literature, there is converging evidence that reparative processes recapitulate early developmental events that lead to dental tissue formation.18Mitsiadis TA, Rahiotis C. Parallels between tooth development and repair: conserved molecular mechanisms following carious and dental injury.
→J Dent Res. 2004 Dec;83(12):896–902.
However, the e ects of platelet-derived growth factor (PDGF) on reparative processes after pulp capping have not been defined. PDGF is a potent mitogenic, chemotactic agent. It stimulates cells of mesenchymal origin to produce protein19Lin Z, Sugai JV, Jin Q, Chandler LA, Giannobile WV. Platelet-derived growth factor-B gene delivery sustains gingival fibroblast signal transduction.
→J Periodontal Res. 2008 Aug;43(4):440–9.
and promotes angiogenesis and the regeneration process of several tissues, such as bone, cementum and periodontal ligament.20Giannobile WV. Periodontal tissue engineering by growth factors.
→Bone. 1996 Jul;19(1 Suppl):23S–37S.
PDGF also regulates cell proliferation and dentin matrix protein production in dental pulp culture.21Nakashima M. The e ects of growth factors on DNA synthesis, proteoglycan synthesis and alkaline phosphatase activity in bovine dental pulp cells.
→Arch Oral Biol. 1992 Mar;37(3):231–6.
22Denholm IA, Moule AJ, Bartold PM. The behaviour and proliferation of human dental pulp cell strains in vitro, and their response to the application of platelet-derived growth factor-BB and insulin-like growth factor-1. →Int Endod J. 1998 Jul;31(4):251–8. In their histochemical and immunohistochemical study, Yokose et al. evaluated the e ects of three PDGF dimers (PDGF-AA, -BB and -AB) on odontoblast di erentiation of dental pulp cells.23Yokose S, Kadokura H, Tajima N, Hasegawa A, Sakagami H, Fujieda K, Katayama T. Platelet-derived growth factor exerts disparate e ects on odontoblast di erentiation depending on the dimers in rat dental pulp cells.
→Cell Tissue Res. 2004 Mar;315(3):375–84.
The authors reported the di erent e ects of the PDGF dimers on dentin formation during the repair process in damaged dental pulp. They observed that PDGF-AB and BB stimulated the di erentiation of odontoblastic cells, increasing the number of mature odontoblastic cells. In contrast, PDGF-AA exerted inhibitory effects on odontoblast di erentiation.24Yokose S, Kadokura H, Tajima N, Hasegawa A, Sakagami H, Fujieda K, Katayama T. Platelet-derived growth factor exerts disparate e ects on odontoblast di erentiation depending on the dimers in rat dental pulp cells.
→Cell Tissue Res. 2004 Mar;315(3):375–84.
These findings suggest a role of PDGF-BB in dentinogenesis in the dental pulp and in di erentiation of odontoblasts during repair processes after injury to the mature pulp. The aims of this preliminary human study were to develop a regenerative approach to pulp capping using PDGF-BB and to describe histologically the pulp tissue response.

Materials and methods

After a through explanation of the experimental rationale, clinical procedure and possible risks, written informed consent was obtained from both subjects to be entered in the study. The study conformed to the principles outlined in the Declaration of Helsinki of 1975, as revised in 2013, on experimentation involving human subjects and was approved by the Ethics Committee of the Department of Human Morphology and Biomedical Sciences “Città Studi”, Milan, Italy. Before treatment, all patients gave written informed consent. Two completely erupted third molars that needed to be extracted for orthodontic treatment were selected from two patients (one tooth from each patient) with the following inclusion criteria: (a) no systemic diseases or metabolic bone disorders; (b) not pregnant; and (c) no history of malignancy, radiotherapy or chemotherapy for a malignancy in the past five years. Furthermore, in order to standardize the age-related prognostic factor, subjects aged between 18 and 39 were enrolled.24 The experimental teeth were clinically and radiographically examined and presented superficial enamel decay; however, the teeth were asymptomatic, without periapical lesions and responded positively to the cold stimulus test performed by applying HYGENIC ENDO-ICE F frozen gas (Coltène/Whaledent, Mahwah, N.J., U.S.) for 5 s to the buccal surfaces.

Procedures employed

Forty days before the extraction, after local and intraligament anesthesia with lidocaine containing 1:80,000 epinephrine to control pain and bleeding from the exposed pulp, the selected molars were isolated with a rubber dam and disinfected with topical antiseptic. Class I cavities on the occlusal surfaces of the experimental teeth were prepared by means of diamond burs (1 mm in diameter) and the pulps were exposed. On one tooth (Site A), a perforation of 1 mm × 1 mm (evaluated at the level of the pulp chamber) was performed; and on the other tooth (Site B), the perforation was 3 mm × 3 mm.

After rising with sterile water to remove the debris, establishing hemostasis with a sterile cotton pellet soaked in saline solution and drying with a sterile cotton pellet, the pulp was capped with sterile cotton embedded in a PDGF-BB solution and covered with zinc oxide cement (CAVIT, 3M ESPE, Seefeld, Germany). During the days after capping, the patients completed a questionnaire on pain occurrence. After 40 days, the experimental teeth were tested for pulp vitality by applying HYGENIC ENDO-ICE F and were carefully extracted without root separation or crown fracture.

Histological analysis

Immediately after extraction, the teeth were immersion fixed in a 10% formalin/0.1 M phosphate-bu ered saline (pH 7.4) for 24 h at room temperature. The dental crown was separated from the roots using a round bur in a low-speed handpiece and then decalcified for 30 days in a solution containing formic acid (625 cm3 in 625 cm3 of distilled/purified water) and sodium citrate (250 g in 125 cm3 of distilled/purified water). Decalcification of dental tissue was verified by radiograph. After rinsing under running water for 48 h, the sample was routinely dehydrated in increasing concentrations of ethanol (from 50 to 100%), immersed in xylol for 12 h and then embedded in para in. Serial buccolingual sections were obtained from 4 to 5 mm and then hydrated in xylol and decreasing concentrations of ethanol (from 100 to 70%) and finally immersed in distilled water. Sections were stained with hematoxylin and eosin (H&E) to evaluate the tissue morphology and with Masson’s trichrome stain to distinguish the connective matrix from cells. The sections were viewed and photographed under a light microscope (Eclipse E600, Nikon, Tokyo, Japan) equipped with a calibrated digital camera (DXM 1200, Nikon). Multiple central sections were used to perform an overall assessment for each tooth. The hard-tissue bridge formation (continuity, morphology, localization and thickness) and the dental pulp reaction (inflammatory cell response and tissue disorganization) were described.

Table. 1
Thickness (mm) of the newly formed bridge measured at three di erent points. The thickness was not evaluated in sites where the bridge was absent.

Results

Both patients (A and B) who completed the study were female, nonsmokers, and 23 and 26 years old, respectively. A total of two teeth were analyzed. After the experimental pulp capping, the patients did not report any symptoms or analgesic intake. At the extraction appointment, both teeth were vital and both cavities still closed with CAVIT. At the histological evaluation, the thickness (mm) of the newly formed hard tissue was measured at three di erent points of the bridge: alongside the dentinal wall (on the mesial side and distal side) and in the center. Table 1 shows the mean thickness of the newly formed bridge.

table-1

Table 1

Fig. 1
Photomicrograph of Site A. Buccolingual section.The drill-created cavity (C) containing much debris is separated from the pulp (P) by a thick and incomplete dentin bridge (DB). The newly formed hard tissue starting from the original dentin tissue covers only half of the exposed pulp. H&E staining (at original 20× magnification).

Site A

In all of the sections, the drill-created cavity contained debris and bacteria along all of the cavity walls (Fig. 1). An incomplete dentin bridge lined the pulp exposure site and was formed by well-organized tubular reparative dentin, with a clear predentin layer and odontoblastic-like cells (Fig. 2).No extensive dentin matrix deposition obliterating the pulp chamber was observed. The general state of the pulp close to the remaining defect was moderately disorganized. This area contained many fibroblasts, some extravasated red blood cells and few inflammatory cells (Fig. 3). No signs of abscess were observed. The pulp tissue adjacent to the reactive area appeared normal, with no signs of inflammation or necrosis (Figs. 4 & 5).

Fig. 2
Detail of Figure 1. The dentin bridge (DB) is formed by tubular and well-oriented reparative dentin. The pulp (P) appears slightly disorganized with few scattered inflammatory cells. C = cavity. H&E staining (at original 100× magnification).

Fig. 3
Detail of Figure 1. The pulp tissue (P) close to the newly formed dentin (DB) and surrounding the remaining defect appears disorganized, with many fibroblasts and few scattered inflammatory cells. H&E staining (at original 200× magnification).

Fig. 4
Detail of Figure 1. The pulp tissue (P) adjacent to the reactive area and under the original dentin (D) appears healthy and well organized, with no signs of necrosis or abscess. H&E staining (at original 100× magnification).

Fig. 5
Detail of Figure 1. Photomicrograph of the pulp in the area adjacent to the reactive tissue. No extravasated red blood cells, su ering pulp or inflammatory cells are detectable. H&E staining (at original 400× magnification).

Site B

Debris occurred along and over the cavity walls, but without touching the pulp tissue (Fig. 6). The hard bridge formation was moderate and incomplete, leaving a small area of communication between the capping material and the dental pulp. The reparative dentin was tubular and well oriented (Fig. 7), without invading the pulp space. The general state of the pulp was normally organized without inflammatory cells beneath the dentin bridge formation. Only a limited area of tissue disorganization and pulp reaction similar to that observed in Site A was adjacent to the hard-barrier interruption and separated the normal pulp tissue from the contaminated drillcreated cavity (Fig. 8). No tunnel-like defect appeared in any section. The hard-tissue thickness was greater in the central portion, and the thickness at the distal side was not calculated because of the interruptions (Table 1).

Fig. 6
Photomicrograph of Site B. Buccolingual section.Within the cavity (C), debris is visible. Between the cavity and the pulp (P), the dentin bridge (DB) runs horizontally from the cut surfaces, covering most of the exposed dental pulp. This hard tissue is very thin on the right side close to the original dentin tissue, is the thickest in the central area of the defect and is incomplete on the left side (black arrow). The dental pulp presents no inflammatory response and has an organized structure, but for the area close to the dentin bridge interruption, where a disorganized and fibrous clot-like tissue is observed. H&E staining (at original 20× magnification).

Fig. 7
Detail of Figure 6. The reparative dentin (DB) is tubular and well organized. Odontoblast-like cells (O) are between the dental pulp (P) and the predentin (PD) tissue. The pulp is well organized and without inflammatory cells. H&E staining (at original 400× magnification).

Fig. 8
Detail of Figure 6. In correspondence with the dentin bridge interruption, the pulp is not in direct contact with the cavity. A disorganized clotlike tissue (Cl) with many fibroblasts (F) and few inflammatory cells is apparent between the cavity and the pulp in close contact with bacteria and debris. Masson’s trichrome staining (original 600× magnification).

Discussion

The present pilot study was designed to evaluate the response of noninflamed mechanically exposed human pulps after capping performed using PDGF-BB. In Site A, an area of moderate disorganization was evident below the remaining pulp exposure site. In Site B, only a limited area of slight reaction was observed at the lateral side of the defect, close to the dentin bridge interruption. No signs of abscess or inflammatory infiltrate in the connective tissue were detected in either sample. The pulp was overall normal and asymptomatic, despite the use of nonsealing cement. Tubular reparative dentin and an adjacent well-organized odontoblast-like cell layer were detected in both samples. No extensive dentin matrix deposition obliterating the pulp chamber was found. In the literature, tunnel defects are often described throughout the newly formed dentin bridges of teeth capped with calcium hydroxide.25Cox CF, Sübay RK, Ostro E, Suzuki S, Suzuki SH. Tunnel defects in dentin bridges: their formation following direct pulp capping. →Oper Dent. 1996 Jan-Feb;21(1):4–11. In the present study, in both samples, the reparative dentin was compact and without defects. Since the aim of the present study was to assess the response of noninflamed pulp tissue after PDGF-BB treatment, no control samples were evaluated to compare the amount of newly formed dentin matrix. Also, the experiment was conducted on a limited number of cases and thus did not allow for statistical analysis. In the treated teeth, access to the pulp chamber was of two di erent sizes to assess the response of capped pulp tissue to varying extents of such a traumatic event.These preliminary findings indicate that PDGF-BB does not elicit pulpal inflammatory response, nor induce extensive dentin matrix deposition, suggesting that this growth factor could be safely applied in human pulp capping. According to previous human models that proved the e icacy of growth factors in noninflamed exposed pulp,26Olsson H, Davies JR, Holst KE, Schröder U, Petersson K. Dental pulp capping: e ect of Emdogain Gel on experimentally exposed human pulps.
→Int Endod J. 2005 Mar;38(3):186–94.
this study was performed on healthy and freshly exposed pulps. However, Rutherford and Gu demonstrated the failure of a treatment strategy utilizing BMP-7 proteins for management of inflamed pulpal wounds.27Rutherford RB, Gu K. Treatment of inflamed ferret dental pulps with recombinant bone morphogenetic protein-7.
→Eur J Oral Sci. 2000 Jun;108(3):202–6.
Despite this, it may be supposed that the therapeutic activity of PDGF-BB is mainly due to the promotion of tissue regeneration than to the resolution of the inflammatory process. Further studies should thus investigate the e icacy of PDGF in promoting newly formed dentin bridges in inflamed pulps and compare this treatment with a biological agent to the gold standard pulp capping agent (MTA).28Nair PN, Duncan HF, Pitt Ford TR, Luder HU. Histological, ultrastructural and quantitative investigations on the response of healthy human pulps to experimental capping with mineral trioxide aggregate: a randomized controlled trial.
→Int Endod J. 2008 Feb;41(2):128–50.
The role and mechanism of action of PDGF in healing of damaged dental pulp and dentin bridge formation are not completely understood. PDGF plays a role in cell chemotaxis, proliferation and di erentiation at each stage of wound healing.29Lin Z, Sugai JV, Jin Q, Chandler LA, Giannobile WV. Platelet-derived growth factor-B gene delivery sustains gingival fibroblast signal transduction.
→J Periodontal Res. 2008 Aug;43(4):440–9.
30Giannobile WV. Periodontal tissue engineering by growth factors.
→Bone. 1996 Jul;19(1 Suppl):23S–37S.
In periodontics, clinical studies have been conducted since PDGF demonstrated an important role in regeneration of cementum, periodontal ligament and alveolar bone.31Giannobile WV, Finkelman RD, Lynch SE. Comparison of canine and non-human primate animal models for periodontal regenerative therapy: results following a single administration of PDGF/IGF-I.
→J Periodontol. 1994 Dec;65(12):1158–68.
In a clinical trial, Nevins et al. evaluated the healing and regeneration of infrabony periodontal defects treated with highly purified recombinant human PDGF-BB and a tricalcium phosphate sca old and demonstrated the e icacy of PDGF-BB in accelerating and improving periodontal soft-tissue healing and bone regeneration.32Nevins M, Giannobile WV, McGuire MK, Kao RT, Mellonig JT, Hinrichs JE, McAllister BS, Murphy KS, McClain PK, Nevins ML, Paquette DW, Han TJ, Reddy MS, Lavin PT, Genco RJ, Lynch SE. Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial.
→J Periodontol. 2005 Dec;76(12):2205–15.
In addition, clinical trials have suggested the promotion of bone turnover during the repair process of tooth-supporting osseous defects.33Sarment DP, Cooke JW, Miller SE, Jin Q, McGuire MK, Kao RT, McClain PK, McAllister BS, Lynch SE, Giannobile WV. E ect of rhPDGF-BB on bone turnover during periodontal repair.
→J Clin Periodontol. 2006 Feb;33(2):135–40.

A histochemical and immunohistochemical study has evaluated the e ects of three PDGF dimers (PDGF-AA, -BB and -AB) on odontoblast di erentiation of dental pulp cells.34Yokose S, Kadokura H, Tajima N, Hasegawa A, Sakagami H, Fujieda K, Katayama T. Platelet-derived growth factor exerts disparate e ects on odontoblast di erentia- tion depending on the dimers in rat dental pulp cells.
→Cell Tissue Res. 2004 Mar;315(3):375–84.
The authors observed dentin formation during the repair process in damaged dental pulp. They also observed that PDGF-AB and -BB stimulated the di erentiation of odontoblast cells, increasing the number of mature odontoblast cells. In contrast, PDGF-AA exerted inhibitory e ects on odontoblast di erentiation.35Yokose S, Kadokura H, Tajima N, Hasegawa A, Sakagami H, Fujieda K, Katayama T. Platelet-derived growth factor exerts disparate e ects on odontoblast di erentia- tion depending on the dimers in rat dental pulp cells.
→Cell Tissue Res. 2004 Mar;315(3):375–84.
These findings suggest a role of PDGF-BB in dentinogenesis in the dental pulp and in di erentiation of odontoblasts during repair processes after injury to the mature pulp. The importance of PDGF in the dental pulp regenerative process is due to the role that this growth factor plays during embryonic development. PDGFs and plateletderived growth factor receptors (PDGFRs) play a role in gastrulation,36Montero JA, Heisenberg CP. Gastrulation dynamics: cells move into focus. →Trends Cell Biol. 2004 Nov;14(11):620–7. development of the cranial and cardiac neural crests,37Tallquist MD, Soriano P. Cell autonomous requirement for PDGFRalpha in populations of cranial and cardiac neural crest cells. →Development. 2003 Feb;130(3):507–18. and formation of the palate.38Xu X, Bringas P, Soriano P, Chai Y. PDGFR-alpha signaling is critical for tooth cusp and palate morphogenesis.
→Dev Dyn. 2005 Jan;232(1):75–84.
Studies have shown that PDGF-and PDGFR-are expressed in developing mouse molars, regulate epithelial–mesenchymal interaction during mammalian tooth morphogenesis, and have a critical function in differentiation of dental pulp cells and in the development of dental cusps.39Xu X, Bringas P, Soriano P, Chai Y. PDGFR-alpha signaling is critical for tooth cusp and palate morphogenesis.
→Dev Dyn. 2005 Jan;232(1):75–84.
40Hu JC, Zhang C, Slavkin HC. The role of platelet-derived growth factor in the development of mouse molars. →Int J Dev Biol. 1995 Dec;39(6):939–45.

Conclusion

Within its limitations, this study suggests that PDGF-BB appears to be a safe pulp capping agent. PDGF-BB may stimulate dentinogenesis, promoting di erentiation of odontoblasts after dental pulp injury. It appears that di erentiated odontoblasts produce tubular and compact reparative dentin, without tunnel defects, and do not obliterate the pulp chamber.

Competing interests

The authors declare that they have no competing interests.

Gaia Pellegrini

Interview

with Dr. Gaia Pellegrini

Why did you conduct the research reported on in this paper?

In recent years, our research group collaborated with some U.S. researchers and we had the opportunity to gain in-depth knowledge regarding the activity of PDGF. In particular, the mitogenic, chemotactic and proangiogenic activity of this protein were studied. In clinical practice, pulp capping agents still have limited efficacy in inducing dentin regeneration after injury. Since data have been published about the stimulating effect of PDGF-BB on the differentiation of odontoblastic cells, on increasing the number of mature odontoblastic cells and on dentin formation during the repair process of injured dental pulp, we decided to evaluate clinically and histologically the response of exposed dental pulps after treatment with PDGF-BB.

For what reasons could others cite your paper?

Because the effect of PDGF on exposed dental pulps is still understudied.

How could your study’s findings have an impact on dentistry?

The findings of the present study are preliminary; however, they may encourage dental researchers to design further studies aimed at a better understanding of the effect of PDGF on human dental pulp.

What is the relevance of your study’s findings to the daily practice of a dentist?

The findings of the present study, if confirmed by further studies with a larger study population and that test this protein in different clinical situations, may have an important impact on the daily practice of dentists.

What are your recommendations for further investigation of the topic of your article?

The recommendations are
– to evaluate histologically the state of the dental pulp after a longer healing period;
– to seal the dental pulp with a composite material after treatment with PDGF-BB; and
– to evaluate the effect of this protein in different clinical situations (e.g., teeth affected by caries or pain).

References   [ + ]

1. Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Robey PG, Shi S. Stem cell properties of human dental pulp stem cells.
→J Dent Res. 2002 Aug;81(8):531–35.
2. Zhu C, Ju B, Ni R. Clinical outcome of direct pulp capping with MTA or calcium hydroxide: a systematic review and meta analysis.
→Int J Clin Exp Med. 2015 Oct; 8(10):17055–60.
3. Komabayashi T, Zhu Q, Eberhart R, Imai Y. Current status of direct pulpcapping materials for permanent teeth. →Dent Mater J. 2016;35(1):1–12.
4. Accorinte ML, Loguercio AD, Reis A, Costa CA. Response of human pulps capped with di erent self-etch adhesive systems.
→Clin Oral Investig. 2008 Jun;12(2):119–27.
5. Cox CF, Tarim B, Kopel H, Gurel G, Hafez A. Technique sensitivity: biological factors contributing to clinical success with various restorative materials.
→Adv Dent Res. 2001 Aug;15(1):85–90.
6. Nakamura Y, Hammarström L, Matsumoto K, Lyngstadaas SP. The induction of reparative dentine by enamel proteins.
→Int Endod J. 2002 May;35(5):407–17.
7. Olsson H, Petersson K, Rohlin M. Formation of a hard tissue barrier after pulp cappings in humans. A systematic review.
→Int Endod J. 2006 Jun;39(6):429–42.
8. Cox CF, Sübay RK, Ostro E, Suzuki S,
Suzuki SH. Tunnel defects in dentin bridges: their formation following direct pulp capping. →Oper Dent. 1996 Jan-Feb;21(1):4–11.
9, 28. Nair PN, Duncan HF, Pitt Ford TR, Luder HU. Histological, ultrastructural and quantitative investigations on the response of healthy human pulps to experimental capping with mineral trioxide aggregate: a randomized controlled trial.
→Int Endod J. 2008 Feb;41(2):128–50.
10. Roberts HW, Toth JM, Berzins DW, Charlton DG. Mineral trioxide aggregate material
use in endodontic treatment: a review of the literature.
→Dent Mater. 2008 Feb;24(2):149–64.
11. Nakashima M. Induction of dentin formation on canine amputated pulp by recombinant human bone morphogenetic proteins (BMP)-2 and -4.
→J Dent Res. 1994 Sep;73(9):1515–22.
12. Dobie K, Smith G, Sloan AJ, Smith AJ. E ects of alginate hydrogels and TGF- 1 on human dental pulp repair in vitro.
→Connect Tissue Res. 2002;43(2-3):387–90.
13. 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 Jul;38(7):571–6.
14. Zhang W, Walboomers XF, Jansen JA. The formation of tertiary dentin after pulp capping with a calcium phosphate cement, loaded with PLGA microparticles containing TGF-beta1.
→J Biomed Mater Res A. 2008 May;85(2):439–4.
15, 26. Olsson H, Davies JR, Holst KE, Schröder U, Petersson K. Dental pulp capping: e ect of Emdogain Gel on experimentally exposed human pulps.
→Int Endod J. 2005 Mar;38(3):186–94.
16. Sabbarini J, Mohamed A, Wahba N, El-Meligy O, Dean J. Comparison of enamel matrix derivative versus formocresol as pulpotomy agents in the primary dentition.
→J Endod. 2008 Mar;34(3):284–7.
17. Nakamura Y, Slaby I, Matsumoto K, Ritchie HH, Lyngstadaas SP. Immunohistochemical characterization of rapid dentin formation induced by enamel matrix derivative. →Calcif Tissue Int. 2004 Sep;75(3):243–52.
18. Mitsiadis TA, Rahiotis C. Parallels between tooth development and repair: conserved molecular mechanisms following carious and dental injury.
→J Dent Res. 2004 Dec;83(12):896–902.
19, 29. Lin Z, Sugai JV, Jin Q, Chandler LA, Giannobile WV. Platelet-derived growth factor-B gene delivery sustains gingival fibroblast signal transduction.
→J Periodontal Res. 2008 Aug;43(4):440–9.
20, 30. Giannobile WV. Periodontal tissue engineering by growth factors.
→Bone. 1996 Jul;19(1 Suppl):23S–37S.
21. Nakashima M. The e ects of growth factors on DNA synthesis, proteoglycan synthesis and alkaline phosphatase activity in bovine dental pulp cells.
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