Histological comparison of formocresol, enamel matrix derivative and turmeric extract as pulpotomy agents in primary teeth

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Asdaq Hussain This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5444035/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background This study aimed to compare and histologically evaluate the pulpal inflammatory response and dentin bridge formation using Formocresol (FC), Enamel Matrix Derivative (EMD), and Turmeric Extract (TE) as pulpotomy agents in primary teeth. Methods Eighty-one patients, aged 8–10 years, requiring both serial extraction and pulpotomy of primary molars were enrolled in this study. One symptomless carious molar tooth from each patient was selected. The participants were divided into three equal groups (n = 27 each) based on the time planned for serial extraction: 1 week, 2 weeks, and 6 months. Each group was subdivided into three sub-groups (n = 9) according to the pulpotomy agent used (FC, EMD, or TE). Histological evaluations were performed post-extraction to assess pulpal inflammatory response and dentin bridge formation. Statistical analysis was carried out using Fisher’s exact test, with a significance threshold set at p < 0.05. Results A statistically significant difference was observed among the three materials regarding pulpal inflammatory response and dentin bridge formation. At 1 week, the FC and EMD groups had moderate inflammation in 88.9% and 77.8% of cases, respectively, while the TE group showed mild inflammation in 55.6% of cases. After 2 weeks, 77.8% of the TE group displayed mild inflammation, 66.7% of the EMD group showed moderate inflammation, and 22.2% of the FC group exhibited severe inflammatory response. By 6 months, 88.9% of the TE group had mild inflammation, while 44.4% of the EMD group showed moderate and 33.3% of the FC group demonstrated severe inflammation. Regarding dentin bridge formation after 6 months, 77.8% of the EMD group exhibited over 75% bridge formation whereas 88.9% of the FC group showed no bridge formation. The TE group showed moderate development with 66.7% showing less than 25% bridge formation. Conclusion TE and EMD demonstrated promising results in this study. Compared to FC, TE showed potential in reducing pulpal inflammation, while EMD was the most effective at promoting dentin bridge formation. However, further studies with extended follow-up are needed to determine the safe clinical indications for these alternative pulpotomy agents in primary teeth. Enamel matrix derivative formocresol pulpotomy turmeric extract Background The integrity of primary dentition is crucial until their normal exfoliation, as it is important for the proper development and maturation of the child, along with the accurate formation of the facial-skeletal complex, ensuring suitable occlusion and good aesthetic qualities [1]. Various stimuli, including chemical factors (bacterial toxins), mechanical insults (heat, trauma), and restorative procedures can distress teeth. These insults can induce inflammatory changes within the tooth structure [2]. Pulpotomy involves the removal of coronal dental pulp that is subjected to inflammation or degenerative changes while maintaining the vitality of radicular pulp tissue. The radicular pulp is then covered with a suitable medicament or dressing to promote healing at the amputation site [3]. Traditionally, Formocresol (FC) has been considered as the "gold standard" for pulpotomy in primary teeth due to its ability to fix the pulp tissue and bactericidal properties [4]. Studies have revealed that FC effectively devitalizes the dental pulp [5]. Although FC has demonstrated high success rate, its use has raised several concerns, including its potential carcinogenic, mutagenic, and allergenic effects [6]. With the recent advances in the understanding of pulp biology and regeneration of the pulp-dentin complex, enamel matrix derivative (EMD, Emdogain®) has been suggested for the regeneration of dental tissues [7,8]. EMD is an extract produced from porcine fetal tooth material, primarily composed of amelogenins, a type of protein recognized for its ability to promote the growth and proliferation of periodontal ligament cells [9]. In regenerative endodontics, the potential of EMD is still not entirely comprehended, but it has been demonstrated that EMD serves a significant role in odontogenesis, augmenting the healing and regeneration of pulp tissue [10]. Herbal and natural medicaments are needed to be investigated as alternative measures in the prevention and treatment of various diseases due to their vital characteristics of safety, effectiveness and economical availability [11]. One such medicine is turmeric ( Curcuma longa ) which is a part of the ginger (Zingiberaceae) family. Constituents of turmeric are called curcuminoids, that comprise mainly curcumin (diferuloylmethane), bisdemethoxycurcumin, and demethoxycurcumin. Curcumin, a yellow colored phenolic compound, is the most significant fraction that is accountable for the biological actions of turmeric [12]. Turmeric extract (TE) has also emerged as a potential pulpotomy agent owing to its anti-inflammatory, antioxidant and antimicrobial properties [13]. Although studies on TE pulpotomy have demonstrated good clinical and radiographic outcomes, histological evaluation is needed to more thoroughly assess the efficacy and healing effects of turmeric on dental pulp [14, 15]. While FC is a commonly used pulpotomy agent with recognized efficacy, the potential benefits of EMD and TE require further investigation. To date, no studies have directly compared the histological response of human dental pulp to FC, EMD, and TE as pulpotomy agents in primary teeth. Therefore, this study aimed to histologically evaluate the pulpal inflammatory response and dentin bridge formation when using FC, EMD, and TE as pulpotomy agents in primary teeth. Methods This comparative study was conducted in the Department of Pediatric Dentistry, de’Montmorency College of Dentistry/Punjab Dental Hospital, Lahore, Pakistan, in collaboration with the Histopathological Laboratory of Post Graduate Medical Institute (PGMI), Lahore, Pakistan. The study approval was obtained from the University of Health Sciences, Lahore (No: UHS/Education/126/2384). Informed consent was obtained from the parents of the patients and/or their legal guardian(s) prior to inclusion in the study. Eighty-one healthy, cooperative children with an age range of 8-10 years requiring serial extraction and pulpotomy of primary molars were selected from the Out Patient Department (OPD) of Pediatric Dentistry Department. Diagnostic periapical radiographs were taken, and tooth vitality tests were performed. The criteria for including teeth in the study were as follows: Primary molar with carious exposure of the vital pulp that required pulpotomy Absence of clinical symptoms or signs of pulp degeneration, including spontaneous pain, pain on percussion, history of swelling, or the presence of sinus tracts No clinical signs of excessive mobility; teeth were considered restorable Absence of radiographic signs of external or internal resorption, as well as no periapical or furcation radiolucencies Physiologic root resorption did not exceed one-third The criteria for excluding teeth were as follows: Non-vital tooth Tooth showing profuse bleeding during pulp amputation Hypoplasia or malformed tooth The sample size of the study was determined using the formula, with reference to the previous study conducted by Sabbarini et al. [16]. Z 1-β = 80 % power of study = 0.84 Z 1-α = 95% level of significance = 1.96 P1 = Clinical success rate of formocresol = 67% P2 = Clinical success rate of enamel matrix derivative = 93 % n = required sample size for each group = 27 Participants were assigned to three equal groups (n = 27) based on the time planned for serial extraction: 1 week, 2 weeks, and 6 months. Each group was subdivided into three sub-groups (n = 9) according to the pulpotomy agent used (FC, EMD, TE) (Table 1). Table 1 Time of extraction and pulpotomy agents used in the study Group Time of Extraction Sub-group Pulpotomy Agent Group 1 1 week Sub-group 1 (n = 9) FC Sub-group 2 (n = 9) EMD Sub-group 3 (n = 9) TE Group 2 2 weeks Sub-group 4 (n = 9) FC Sub-group 5 (n = 9) EMD Sub-group 6 (n = 9) TE Group 3 6 months Sub-group 7 (n = 9) FC Sub-group 8 (n = 9) EMD Sub-group 9 (n = 9) TE After achieving adequate anesthesia with 2% lidocaine 1:100000 epinephrine, and rubber dam isolation, the caries was removed and the pulpotomy was performed. Occlusal cavities were prepared with a No. 245 bur (DENTSPLY, USA) under air-water spray coolant, followed by removal of the coronal pulp chamber roof and coronal pulp using a high-speed bur and a spoon excavator. The pulp chamber was irrigated with saline to clear away any debris. Hemostasis was achieved by gently pressing a sterilized, moistened cotton pellet against the amputated pulp stumps in all three groups. If hemostasis was not achieved, a pulpectomy or extraction was performed, resulting in an exclusion of the tooth from the study. Following hemostasis, pulpotomy agents were applied as follows: FC Group: A sterile cotton pellet moistened with 1:5 diluted Buckley’s formocresol (Sultan Chemists Inc, Englewood, NJ, USA) was placed against the pulpal stumps for 5 minutes. EMD Group: The amputated pulpal stumps were covered with Emdogain® (Biora AB Malmö, Sweden). TE Group: Amputated pulpal stumps were covered with aqueous TE. The aqueous turmeric extract was prepared using 200 grams of ground turmeric powder, drying it in an oven for 24 hours at 40°C, and then boiling it in 500 ml of distilled water. After boiling, the solution was spray-dried to create a paste [17]. A zinc oxide and eugenol (ZOE) base was placed over the pulpal stumps of the treated teeth followed by a light-cured glass ionomer cement. The extracted samples were preserved in 10% buffered formalin solution (10% Neutral Buffered Formalin, Thomas Scientific LLC, New Jersey, United States) for 48 hours, with the apical foramina sealed with wax. Demineralization was carried out in 5% trichloro-acetic acid. Samples were embedded in paraffin wax block (Clear Paraffin Block, EverBio Technology INC., New Taipei City, Taiwan). Longitudinal sections (5μm thick) were prepared, processed, and stained utilizing Hematoxylin & Eosin staining (H&E Staining Kit, Abcam, England, United Kingdom), and then evaluated by a histopathologist utilizing a light microscope (Leica Microscope DM2500, Leica, Hesse, Germany). The histopathological features assessed included inflammatory cell response and dentin bridge formation. Inflammatory Cell Response The pulpal inflammatory response was scored based on predefined criteria by Aeinehchi et al. [18] as follows: Grade 0: Absence of inflammatory cells. Grade 1: Mild inflammation, characterized by fewer than 30 inflammatory cells. Grade 2: Moderate inflammation, defined as having more than 30 and less than 60 inflammatory cells. Grade 3: Severe inflammation, indicated by 60 or more inflammatory cells. Dentin Bridge Formation The assessment of bridge formation followed the criteria according to a modified scoring system adapted from Stanley [19]: Score 0: Absence of dentin bridge formation Score 1: Bridge formation is less than 25%. Score 2: Bridge formation is more than 25% but less than 50%. Score 3: Bridge formation is more than 50% but less than 75%. Score 4: Bridge formation exceeds 75%. Statistical analysis The data were analyzed with Statistical Package for Social Sciences (SPSS) software, version 23.0. Inflammatory cell count and dentin bridge formation were presented as frequencies and percentages. Fisher’s exact test was employed to compare these scores among the groups. A p-value of ≤ 0.05 was considered statistically significant. Results Inflammatory Cell Response At 1-week, histological evaluation of the inflammatory cell response showed that none of the specimens in the FC, EMD, or TE groups exhibited an absence of inflammatory cells (Grade 0). Moderate focal accumulations of inflammatory cells (Grade 2) were seen in the majority of FC and EMD specimens (88.9% and 77.8%, respectively). In contrast, the TE group displayed mild (Grade 1) to moderate (Grade 2) scattering of inflammatory cells in 55.6% and 44.4% of the cases, respectively. These results were statistically significant (p = 0.005) (Table 2). After 2 weeks, again, none of the cases in the FC, EMD, or TE groups showed a Grade 0 inflammatory response. A decrease in inflammatory rection was found in the TE group, with 77.8% exhibiting a mild inflammatory response, while 66.7% of the EMD group showed moderate inflammation. However, the FC group demonstrated an increased severe inflammatory response affecting 22.2% of the cases. These findings were statistically significant (p = 0.004) (Table 2). After 6 months, while none of the specimens in any group showed absence of inflammation, the majority (88.9%) of cases in the TE group demonstrated only a mild inflammatory response. In contrast, 44.4% of cases in the EMD showed a moderate response and 33.3% in the FC group exhibited a severe inflammatory response. The differences between the groups were statistically significant (p = 0.001) (Table 2). Table 2 Comparison of inflammatory cell response after different interval among groups Time Point Group Grade 0 n (%) Grade 1 n (%) Grade 2 n (%) Grade 3 n (%) p-value 1 Week FC 0 (0%) 0 (0%) 8 (88.9%) 1 (11.1%) 0.005* EMD 0 (0%) 0 (0%) 7 (77.8%) 2 (22.2%) TE 0 (0%) 5 (55.6%) 4 (44.4%) 0 (0%) 2 Weeks FC 0 (0%) 0 (0%) 7 (77.8%) 2 (22.2%) 0.004* EMD 0 (0%) 2 (22.2%) 6 (66.7%) 1 (11.1%) TE 0 (0%) 7 (77.8%) 2 (22.2%) 0 (0%) 6 Months FC 0 (0%) 0 (0%) 6 (66.7%) 3 (33.3%) 0.001* EMD 0 (0%) 5 (55.6%) 4 (44.4%) 0 (0%) TE 0 (0%) 8 (88.9%) 1 (11.1%) 0 (0%) Abbreviations: FC, Formocresol; EMD, Enamel Matrix Derivative; TE, Turmeric Extract. *Statistically significant Dentin Bridge Formation Histological evaluation revealed that most of the EMD group (77.8%) exhibited more than 75% bridge formation (Score 4), while the remaining 22.2% showed more than 50% dentin tissue deposition (Score 3). In contrast, the majority (88.9%) of the specimens in the FC group demonstrated no dentin bridge formation (Score 0), with only 11.1% exhibiting less than 25% bridge formation (Score 1). The TE group demonstrated a moderate development, with 66.7% showing less than 25% bridge formation (Score 1) and 33.3% exhibiting no dentin bridge formation (Score 0). These results were statistically significant (p < 0.001) (Table 3). Table 3 Comparison of dentin bridge formation after six months interval among groups Group Score 0 n (%) Score 1 n (%) Score 2 n (%) Score 3 n (%) Score 4 n (%) p-value FC 8 (88.9%) 1 (11.1%) 0 (0%) 0 (0%) 0 (0%) < 0.001* EMD 0 (0%) 0 (0%) 0 (0%) 2 (22.2%) 7 (77.8%) TE 3 (33.3%) 6 (66.7%) 0 (0%) 0 (0%) 0 (0%) Abbreviations: FC, Formocresol; EMD, Enamel Matrix Derivative; TE, Turmeric Extract. *Statistically significant Discussion The results of the histological evaluation in this study offer important insights into the efficacy of Formocresol (FC), Enamel Matrix Derivative (EMD) and Turmeric Extract (TE) as pulpotomy agents for primary teeth. Statistically significant difference was found in the pulpal inflammatory response and dentin bridge formation among the three agents. A better inflammatory response was shown by TE, whereas EMD displayed superior dentin bridge formation after 6 months. Turmeric extract demonstrated lower levels of inflammation at all time points compared to FC and EMD, indicating its effectiveness in reducing inflammation. Similar effect of TE was seen in previous studies [14, 15]. The ability of turmeric to modulate inflammation may be due to its bioactive compounds, which have been shown to inhibit pro-inflammatory cytokines and promote tissue repair [20]. Research indicates that curcumin, a highly versatile molecule found in turmeric, can interact with various molecular targets linked with inflammation. It has been shown to have strong anti-inflammatory, antioxidant, and immunomodulatory properties [21]. Significantly higher dentin bridge formation was found in the EMD group compared to the FC group after 6 months. This result is consistent with the understanding that EMD can stimulate differentiation of odontoblasts and enhance dentinogenesis, making it an effective agent for regeneration [22]. Several studies have revealed that when used as an adjunct to conservative pulp treatments, such as pulpotomy or direct pulp capping, EMD promotes the formation of reparative dentin, thereby protecting the pulp tissue and helping to prevent pulp degeneration [23, 24, 25]. Meanwhile, moderate bridge formation was found in the TE group, emphasizing the need for additional investigation into its regenerative capabilities. This moderate bridge formation aligns with prior research indicating that turmeric promotes healing and regeneration, offering a promising natural alternative to synthetic materials [15]. Dental pulp comprises different cell types, including immune cells, inflammatory cells, and dormant progenitor cells that mainly play a role in self-renewal [26]. When the pulp is injured, these progenitor cells are assembled to the site of damage. Their growth and differentiation into odontoblast-like cells result in matrix formation and successive mineralization [27]. Therefore, it is reasonable to assume that there is an inherent relationship between the host immune system and potent odontoblasts that regulate differentiation and the dentinogenic response. This intricate interplay between inflammatory cells and odontoblasts for recovery after an injury necessitates a harmonious environment [28]. Turmeric possesses strong anti-inflammatory properties. The anti-inflammatory action of curcumin is partly because of the fact that it inhibits phospholipase D (PLD) which is G protein mediated enzyme [29]. Curcumin also inhibits the production of interleukin-1 and tumor necrosis factor alpha, two main cytokine players produced from macrophages and monocytes that regulates inflammatory responses [30]. Additionally, turmeric promotes wound healing and tissue repair, a complex process which is achieved by modulating collagen, increasing proliferation of endothelial cells and decreasing reactive oxygen species [31]. It also increases the localization of fibronectin and transforming growth factor beta, which are essential components in the process of wound healing [32]. Prior research exhibits that pulpotomy of primary molars is under shift from “standard chemically synthesized pulpotomy medicaments” towards natural products [33]. In the past few years, use of natural products as pulpotomy agent is important, owing to their fewer side effects, ease of availability and financial considerations in developing countries [11]. As a natural and biocompatible substance, curcumin emerges as a promising agent for pulpotomy treatment in primary teeth. Its less water solubility makes it an appropriate entrant for topical applications. Additionally, previous studies have demonstrated that curcumin can enhance cell viability and promote the proliferation of primary dental pulp fibroblasts [4]. To the best of our knowledge, this study could be the first to compare FC with EMD and TE as pulpotomy agents for primary teeth. Previous studies have utilized various biocompatible materials, including platelet‑rich fibrin, bone morphogenic protein, platelet-rich plasma and Emdogain gel which release growth factors after certain period [14, 15, 16]. However, the present study directly applied turmeric extract in deciduous teeth, resulting in satisfactory histological outcomes. Previous studies employed radiographs [14, 15], Micro-CT [34], and histological evaluation [27, 35] to investigate dentin bridge formation. In this study, we opted for histological evaluation, as it is more reliable than radiographs for detecting dentin bridge formation [36] and offers a more detailed understanding of the regenerative characteristics following the application of each tested material. Additionally, it is the only method that allows for an accurate assessment of the pulpal response to the materials used. The small sample size restricts the generalizability of the findings, and the relatively short duration of follow-up may not capture long-term clinical outcomes, as longer periods could reveal potential clinical failures. To enhance the quality and applicability of future research, larger-scale studies with extended follow-up periods are recommended. Furthermore, given the promising results of natural products like turmeric as pulpotomy agents, further investigation into their safety and biocompatibility should be encouraged. Utilizing locally available resources, such as turmeric in regions with high production, can offer a cost-effective alternative to synthetic materials, potentially reducing healthcare costs in developing countries. Conclusion Turmeric extract and enamel matrix derivative demonstrated promising results in this study. Compared to formocresol, turmeric extract showed potential in reducing pulpal inflammation, while enamel matrix derivative was the most effective at promoting dentin bridge formation. However, further studies with extended follow-up are needed to determine the safe clinical indications for these alternative pulpotomy agents in primary teeth. Abbreviations FC Formocresol EMD Enamel matrix derivative TE Turmeric extract PGMI Post graduate medical institute UHS University of Health Sciences OPD Outpatient department SPSS Statistical package for social sciences ZOE Zinc oxide eugenol CT Computed tomography. Declarations Ethics approval and consent to participate The study approval was obtained from the University of Health Sciences, Lahore (No: UHS/Education/126/2384). Informed consent was obtained from the parents of the patients and/or their legal guardian(s) prior to inclusion in the study. Consent for publication Not applicable. Availability of data and materials The datasets used during the present study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding The present study didn’t receive any funding. Authors' contributions NB – Conception, investigation, data curation, methodology, project administration, writing-original draft, writing-review & editing. SN – methodology, supervision, validation and reviewed manuscript. RD – project administration, validation and reviewed manuscript. SK – visualization, data analysis, data interpretation and writing-review & editing. MAH – statistical analysis, data interpretation, writing-original draft, writing-review & editing. All authors read and approved the final manuscript. Acknowledgements None. References Gupta N, Bhat M, Devi P, Girish. Aloe-Vera: A Nature's Gift to Children. Int J Clin Pediatr Dent. 2010;3(2):87–92. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5444035","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":387365917,"identity":"03065e2d-0f86-462e-b281-7b5528e4754b","order_by":0,"name":"Nazia Bashir","email":"","orcid":"","institution":"de’Montmorency College of Dentistry","correspondingAuthor":false,"prefix":"","firstName":"Nazia","middleName":"","lastName":"Bashir","suffix":""},{"id":387365918,"identity":"b38c7c7a-db7a-4ad0-9072-b482483c6942","order_by":1,"name":"Shazia Naz","email":"","orcid":"","institution":"de’Montmorency College of Dentistry","correspondingAuthor":false,"prefix":"","firstName":"Shazia","middleName":"","lastName":"Naz","suffix":""},{"id":387365919,"identity":"436eca99-9eab-429f-8006-b610de9cc899","order_by":2,"name":"Rabia Dastgeer","email":"","orcid":"","institution":"Gulab Devi Chest Hospital","correspondingAuthor":false,"prefix":"","firstName":"Rabia","middleName":"","lastName":"Dastgeer","suffix":""},{"id":387365920,"identity":"b80454e8-3595-4d79-852d-61b70ddbd163","order_by":3,"name":"Samina Khatoon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFUlEQVRIiWNgGAWjYJCCAwwMCQkQpkENMz+ITiggRgsbiFlxjF2yAaTFgKBFMC1nmPkNDoCtw61Wvv104uGCmrQ8/vnNBx8XtrFJG59fnfjhgQGDPL/YAaxaDM7kbjg841hOscQxtmTjmW0yxmY33m6WADrMcObsBOxaGIBaeNgqEhuO8ZhJ87axJZvdOLsBpCXB4DZ2LfL9b4Fa/lUkzodoYa7fPOPs5h/4tDDcANrC25aTuAGkhecMM7MBf+82vLYY3ADawtuXlrjxWFqyMU/FMWaJG7zbLBIMJHD6Rb4/d/Nnnm/JifMOHz74mAcUlf1nN9/8UWEjzy+Nw2GYQAKsUoJY5SDAf4AU1aNgFIyCUTACAADVJ2QKtl1eXwAAAABJRU5ErkJggg==","orcid":"","institution":"National Medical College","correspondingAuthor":true,"prefix":"","firstName":"Samina","middleName":"","lastName":"Khatoon","suffix":""},{"id":387365921,"identity":"c9501bae-77d1-45be-86f2-9f7d1da8fe8d","order_by":4,"name":"Md. Asdaq Hussain","email":"","orcid":"","institution":"National Medical College","correspondingAuthor":false,"prefix":"","firstName":"Md.","middleName":"Asdaq","lastName":"Hussain","suffix":""}],"badges":[],"createdAt":"2024-11-13 05:53:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5444035/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5444035/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85050535,"identity":"71d7c81a-3ed2-49d7-8d84-420aef529a65","added_by":"auto","created_at":"2025-06-20 11:23:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":737905,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5444035/v1/75a4b721-5553-472d-a2b1-31dc9e266f33.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Histological comparison of formocresol, enamel matrix derivative and turmeric extract as pulpotomy agents in primary teeth","fulltext":[{"header":"Background","content":"\u003cp\u003eThe integrity of primary dentition is crucial until their normal exfoliation, as it is important for the proper development and maturation of the child, along with the accurate formation of the facial-skeletal complex, ensuring suitable occlusion and good aesthetic qualities [1]. Various stimuli, including chemical factors (bacterial toxins), mechanical insults (heat, trauma), and restorative procedures can distress teeth. These insults can induce inflammatory changes within the tooth structure [2]. Pulpotomy involves the removal of coronal dental pulp that is subjected to inflammation or degenerative changes while maintaining the vitality of radicular pulp tissue. The radicular pulp is then covered with a suitable medicament or dressing to promote healing at the amputation site [3].\u003c/p\u003e \u003cp\u003eTraditionally, Formocresol (FC) has been considered as the \"gold standard\" for pulpotomy in primary teeth due to its ability to fix the pulp tissue and bactericidal properties [4]. Studies have revealed that FC effectively devitalizes the dental pulp [5]. Although FC has demonstrated high success rate, its use has raised several concerns, including its potential carcinogenic, mutagenic, and allergenic effects [6].\u003c/p\u003e \u003cp\u003eWith the recent advances in the understanding of pulp biology and regeneration of the pulp-dentin complex, enamel matrix derivative (EMD, Emdogain\u0026reg;) has been suggested for the regeneration of dental tissues [7,8]. EMD is an extract produced from porcine fetal tooth material, primarily composed of amelogenins, a type of protein recognized for its ability to promote the growth and proliferation of periodontal ligament cells [9]. In regenerative endodontics, the potential of EMD is still not entirely comprehended, but it has been demonstrated that EMD serves a significant role in odontogenesis, augmenting the healing and regeneration of pulp tissue [10].\u003c/p\u003e \u003cp\u003eHerbal and natural medicaments are needed to be investigated as alternative measures in the prevention and treatment of various diseases due to their vital characteristics of safety, effectiveness and economical availability [11]. One such medicine is turmeric (\u003cem\u003eCurcuma longa\u003c/em\u003e) which is a part of the ginger (Zingiberaceae) family. Constituents of turmeric are called curcuminoids, that comprise mainly curcumin (diferuloylmethane), bisdemethoxycurcumin, and demethoxycurcumin. Curcumin, a yellow colored phenolic compound, is the most significant fraction that is accountable for the biological actions of turmeric [12]. Turmeric extract (TE) has also emerged as a potential pulpotomy agent owing to its anti-inflammatory, antioxidant and antimicrobial properties [13]. Although studies on TE pulpotomy have demonstrated good clinical and radiographic outcomes, histological evaluation is needed to more thoroughly assess the efficacy and healing effects of turmeric on dental pulp [14, 15].\u003c/p\u003e \u003cp\u003eWhile FC is a commonly used pulpotomy agent with recognized efficacy, the potential benefits of EMD and TE require further investigation. To date, no studies have directly compared the histological response of human dental pulp to FC, EMD, and TE as pulpotomy agents in primary teeth. Therefore, this study aimed to histologically evaluate the pulpal inflammatory response and dentin bridge formation when using FC, EMD, and TE as pulpotomy agents in primary teeth.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis comparative study was conducted in the Department of Pediatric Dentistry, de\u0026rsquo;Montmorency College of Dentistry/Punjab Dental Hospital, Lahore, Pakistan, in collaboration with the Histopathological Laboratory of Post Graduate Medical Institute (PGMI), Lahore, Pakistan. The study approval was obtained from the University of Health Sciences, Lahore (No: UHS/Education/126/2384). Informed consent was obtained from the parents of the patients and/or their legal guardian(s) prior to inclusion in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEighty-one healthy, cooperative children with an age range of 8-10 years requiring serial extraction and pulpotomy of primary molars were selected from the Out Patient Department (OPD) of Pediatric Dentistry Department. Diagnostic periapical radiographs were taken, and tooth vitality tests were performed. The criteria for including teeth in the study were as follows:\u0026nbsp;\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003ePrimary molar with carious exposure of the vital pulp that required pulpotomy\u003c/li\u003e\n \u003cli\u003eAbsence of clinical symptoms or signs of pulp degeneration, including spontaneous pain, pain on percussion, history of swelling, or the presence of sinus tracts\u003c/li\u003e\n \u003cli\u003eNo clinical signs of excessive mobility; teeth were considered restorable\u003c/li\u003e\n \u003cli\u003eAbsence of radiographic signs of external or internal resorption, as well as no periapical or furcation radiolucencies\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePhysiologic root resorption did not exceed one-third\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe criteria for excluding teeth were as follows:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eNon-vital tooth\u003c/li\u003e\n \u003cli\u003eTooth showing profuse bleeding during pulp amputation\u003c/li\u003e\n \u003cli\u003eHypoplasia or malformed tooth\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe sample size of the study was determined using the formula, with reference to the previous study conducted by Sabbarini et al. [16].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cimg src=\"data:image/png;base64,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\" alt=\"image\"\u003e\u003c/p\u003e\n\u003cp\u003eZ\u003csub\u003e1-\u0026beta;\u003c/sub\u003e = 80 % power of study = 0.84\u003c/p\u003e\n\u003cp\u003eZ\u003csub\u003e1-\u0026alpha;\u003c/sub\u003e = 95% level of significance = 1.96\u003c/p\u003e\n\u003cp\u003eP1 = Clinical success rate of formocresol = 67%\u003c/p\u003e\n\u003cp\u003eP2 = Clinical success rate of enamel matrix derivative = 93 %\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;n = required sample size for each group = 27\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eParticipants were assigned to three equal groups (n = 27) based on the time planned for serial extraction: 1 week, 2 weeks, and 6 months. Each group was subdivided into three sub-groups (n = 9) according to the pulpotomy agent used (FC, EMD, TE) (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Time of extraction and pulpotomy agents used in the study\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" width=\"600\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTime of Extraction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSub-group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ePulpotomy Agent\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eGroup 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003e1 week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSub-group 1 (n = 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSub-group 2 (n = 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEMD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSub-group 3 (n = 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eGroup 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003e2 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSub-group 4 (n = 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSub-group 5 (n = 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEMD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSub-group 6 (n = 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003eGroup 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSub-group 7 (n = 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eFC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSub-group 8 (n = 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEMD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSub-group 9 (n = 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAfter achieving adequate anesthesia with 2% lidocaine 1:100000 epinephrine, and rubber dam isolation, the caries was removed and the pulpotomy was performed. Occlusal cavities were prepared with a No. 245 bur (DENTSPLY, USA) under air-water spray coolant, followed by removal of the coronal pulp chamber roof and coronal pulp using a high-speed bur and a spoon excavator. The pulp chamber was irrigated with saline to clear away any debris. Hemostasis was achieved by gently pressing a sterilized, moistened cotton pellet against the amputated pulp stumps in all three groups. If hemostasis was not achieved, a pulpectomy or extraction was performed, resulting in an exclusion of the tooth from the study. Following hemostasis, pulpotomy agents were applied as follows:\u003c/p\u003e\n\u003cp\u003eFC Group: A sterile cotton pellet moistened with 1:5 diluted Buckley\u0026rsquo;s formocresol (Sultan Chemists Inc, Englewood, NJ, USA) was placed against the pulpal stumps for 5 minutes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEMD Group: The amputated pulpal stumps were covered with Emdogain\u0026reg; (Biora AB Malm\u0026ouml;, Sweden).\u003c/p\u003e\n\u003cp\u003eTE Group: Amputated pulpal stumps were covered with aqueous TE. The aqueous turmeric extract was prepared using 200 grams of ground turmeric powder, drying it in an oven for 24 hours at 40\u0026deg;C, and then boiling it in 500 ml of distilled water. After boiling, the solution was spray-dried to create a paste [17].\u003c/p\u003e\n\u003cp\u003eA zinc oxide and eugenol (ZOE) base was placed over the pulpal stumps of the treated teeth followed by a light-cured glass ionomer cement. The extracted samples were preserved in 10% buffered formalin solution (10% Neutral Buffered Formalin, Thomas Scientific LLC, New Jersey, United States) for 48 hours, with the apical foramina sealed with wax. Demineralization was carried out in 5% trichloro-acetic acid. Samples were embedded in paraffin wax block (Clear Paraffin Block, EverBio Technology INC., New Taipei City, Taiwan). Longitudinal sections (5\u0026mu;m thick) were prepared, processed, and stained utilizing Hematoxylin \u0026amp; Eosin staining (H\u0026amp;E Staining Kit, Abcam, England, United Kingdom), and then evaluated by a histopathologist utilizing a light microscope (Leica Microscope DM2500, Leica, Hesse, Germany). The histopathological features assessed included inflammatory cell response and dentin bridge formation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInflammatory Cell Response\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe pulpal inflammatory response was scored based on predefined criteria by Aeinehchi et al. [18] as follows:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eGrade 0: Absence of inflammatory cells.\u003c/li\u003e\n \u003cli\u003eGrade 1: Mild inflammation, characterized by fewer than 30 inflammatory cells.\u003c/li\u003e\n \u003cli\u003eGrade 2: Moderate inflammation, defined as having more than 30 and less than 60 inflammatory cells.\u003c/li\u003e\n \u003cli\u003eGrade 3: Severe inflammation, indicated by 60 or more inflammatory cells.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eDentin Bridge Formation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe assessment of bridge formation followed the criteria according to a modified scoring system adapted from Stanley [19]:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eScore 0: Absence of dentin bridge formation\u003c/li\u003e\n \u003cli\u003eScore 1: Bridge formation is less than 25%.\u003c/li\u003e\n \u003cli\u003eScore 2: Bridge formation is more than 25% but less than 50%.\u003c/li\u003e\n \u003cli\u003eScore 3: Bridge formation is more than 50% but less than 75%.\u003c/li\u003e\n \u003cli\u003eScore 4: Bridge formation exceeds 75%.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data were analyzed with Statistical Package for Social Sciences (SPSS) software, version 23.0. Inflammatory cell count and dentin bridge formation were presented as frequencies and percentages. Fisher\u0026rsquo;s exact test was employed to compare these scores among the groups. A p-value of \u0026le; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eInflammatory Cell Response\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt 1-week, histological evaluation of the inflammatory cell response showed that none of the specimens in the FC, EMD, or TE groups exhibited an absence of inflammatory cells (Grade 0). Moderate focal accumulations of inflammatory cells (Grade 2) were seen in the majority of FC and EMD specimens (88.9% and 77.8%, respectively). In contrast, the TE group displayed mild (Grade 1) to moderate (Grade 2) scattering of inflammatory cells in 55.6% and 44.4% of the cases, respectively. These results were statistically significant (p = 0.005) (Table 2).\u003c/p\u003e\n\u003cp\u003eAfter 2 weeks, again, none of the cases in the FC, EMD, or TE groups showed a Grade 0 inflammatory response. A decrease in inflammatory rection was found in the TE group, with 77.8% exhibiting a mild inflammatory response, while 66.7% of the EMD group showed moderate inflammation. However, the FC group demonstrated an increased severe inflammatory response affecting 22.2% of the cases. These findings were statistically significant (p = 0.004) (Table 2).\u003c/p\u003e\n\u003cp\u003eAfter 6 months, while none of the specimens in any group showed absence of inflammation, the majority (88.9%) of cases in the TE group demonstrated only a mild inflammatory response. In contrast, 44.4% of cases in the EMD showed a moderate response and 33.3% in the FC group exhibited a severe inflammatory response. The differences between the groups were statistically significant (p = 0.001) (Table 2).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Comparison of inflammatory cell response after different interval among groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" width=\"602\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime Point\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 0\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 1\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade 3\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 Week\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003eFC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e8 (88.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (11.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 53px;\"\u003e\n \u003cp\u003e0.005*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003eEMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e7 (77.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e2 (22.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e5 (55.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e4 (44.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2 Weeks\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003eFC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 100px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e7 (77.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e2 (22.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 53px;\"\u003e\n \u003cp\u003e0.004*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003eEMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e2 (22.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e6 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e1 (11.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e7 (77.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e2 (22.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6 Months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003eFC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e6 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e3 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 53px;\"\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003eEMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e5 (55.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e4 (44.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 101px;\"\u003e\n \u003cp\u003e8 (88.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 105px;\"\u003e\n \u003cp\u003e1 (11.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: FC, Formocresol; EMD, Enamel Matrix Derivative; TE, Turmeric Extract. *Statistically significant\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDentin Bridge Formation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHistological evaluation revealed that most of the EMD group (77.8%) exhibited more than 75% bridge formation (Score 4), while the remaining 22.2% showed more than 50% dentin tissue deposition (Score 3). In contrast, the majority (88.9%) of the specimens in the FC group demonstrated no dentin bridge formation (Score 0), with only 11.1% exhibiting less than 25% bridge formation (Score 1). The TE group demonstrated a moderate development, with 66.7% showing less than 25% bridge formation (Score 1) and 33.3% exhibiting no dentin bridge formation (Score 0). These results were statistically significant (p \u0026lt; 0.001) (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 Comparison of dentin bridge formation after six months interval among groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" width=\"606\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eScore 0\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eScore 1\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eScore 2\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eScore 3\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eScore 4\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8 (88.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1 (11.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003e\u0026lt; 0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eEMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (22.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (77.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: FC, Formocresol; EMD, Enamel Matrix Derivative; TE, Turmeric Extract. *Statistically significant\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of the histological evaluation in this study offer important insights into the efficacy of Formocresol (FC), Enamel Matrix Derivative (EMD) and Turmeric Extract (TE) as pulpotomy agents for primary teeth. Statistically significant difference was found in the pulpal inflammatory response and dentin bridge formation among the three agents. A better inflammatory response was shown by TE, whereas EMD displayed superior dentin bridge formation after 6 months. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTurmeric extract demonstrated lower levels of inflammation at all time points compared to FC and EMD, indicating its effectiveness in reducing inflammation. Similar effect of TE was seen in previous studies [14, 15]. The ability of turmeric to modulate inflammation may be due to its bioactive compounds, which have been shown to inhibit pro-inflammatory cytokines and promote tissue repair [20]. Research indicates that curcumin, a highly versatile molecule found in turmeric, can interact with various molecular targets linked with inflammation. It has been shown to have strong anti-inflammatory, antioxidant, and immunomodulatory properties [21].\u003c/p\u003e\n\u003cp\u003eSignificantly higher dentin bridge formation was found in the EMD group compared to the FC group after 6 months. This result is consistent with the understanding that EMD can stimulate differentiation of odontoblasts and enhance dentinogenesis, making it an effective agent for regeneration [22]. Several studies have revealed that when used as an adjunct to conservative pulp treatments, such as pulpotomy or direct pulp capping, EMD promotes the formation of reparative dentin, thereby protecting the pulp tissue and helping to prevent pulp degeneration [23, 24, 25]. Meanwhile, moderate bridge formation was found in the TE group, emphasizing the need for additional investigation into its regenerative capabilities. This moderate bridge formation aligns with prior research indicating that turmeric promotes healing and regeneration, offering a promising natural alternative to synthetic materials [15].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDental pulp comprises different cell types, including immune cells, inflammatory cells, and dormant progenitor cells that mainly play a role in self-renewal [26]. When the pulp is injured, these progenitor cells are assembled to the site of damage. Their growth and differentiation into odontoblast-like cells result in matrix formation and successive mineralization [27]. Therefore, it is reasonable to assume that there is an inherent relationship between the host immune system and potent odontoblasts that regulate differentiation and the dentinogenic response. This intricate interplay between inflammatory cells and odontoblasts for recovery after an injury necessitates a harmonious environment [28].\u003c/p\u003e\n\u003cp\u003eTurmeric possesses strong anti-inflammatory properties. The anti-inflammatory action of curcumin is partly because of the fact that it inhibits phospholipase D (PLD) which is G protein mediated enzyme [29]. Curcumin also inhibits the production of interleukin-1 and tumor necrosis factor alpha, two main cytokine players produced from macrophages and monocytes that regulates inflammatory responses [30]. Additionally, turmeric promotes wound healing and tissue repair, a complex process which is achieved by modulating collagen, increasing proliferation of endothelial cells and decreasing reactive oxygen species [31]. It also increases the localization of fibronectin and transforming growth factor beta, which are essential components in the process of wound healing [32].\u003c/p\u003e\n\u003cp\u003ePrior research exhibits that pulpotomy of primary molars is under shift from \u0026ldquo;standard chemically synthesized pulpotomy medicaments\u0026rdquo; towards natural products [33]. In the past few years, use of natural products as pulpotomy agent is important, owing to their fewer side effects, ease of availability and financial considerations in developing countries [11]. As a natural and biocompatible substance, curcumin emerges as a promising agent for pulpotomy treatment in primary teeth. Its less water solubility makes it an appropriate entrant for topical applications. Additionally, previous studies have demonstrated that curcumin can enhance cell viability and promote the proliferation of primary dental pulp fibroblasts [4].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo the best of our knowledge, this study could be the first to compare FC with EMD and TE as pulpotomy agents for primary teeth. Previous studies have utilized various biocompatible materials, including platelet‑rich fibrin, bone morphogenic protein, platelet-rich plasma and Emdogain gel which release growth factors after certain period [14, 15, 16]. However, the present study directly applied turmeric extract in deciduous teeth, resulting in satisfactory histological outcomes. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePrevious studies employed radiographs [14, 15], Micro-CT [34], and histological evaluation [27, 35] to investigate dentin bridge formation. In this study, we opted for histological evaluation, as it is more reliable than radiographs for detecting dentin bridge formation [36] and offers a more detailed understanding of the regenerative characteristics following the application of each tested material. Additionally, it is the only method that allows for an accurate assessment of the pulpal response to the materials used.\u003c/p\u003e\n\u003cp\u003eThe small sample size restricts the generalizability of the findings, and the relatively short duration of follow-up may not capture long-term clinical outcomes, as longer periods could reveal potential clinical failures. To enhance the quality and applicability of future research, larger-scale studies with extended follow-up periods are recommended. Furthermore, given the promising results of natural products like turmeric as pulpotomy agents, further investigation into their safety and biocompatibility should be encouraged. Utilizing locally available resources, such as turmeric in regions with high production, can offer a cost-effective alternative to synthetic materials, potentially reducing healthcare costs in developing countries.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTurmeric extract and enamel matrix derivative demonstrated promising results in this study. Compared to formocresol, turmeric extract showed potential in reducing pulpal inflammation, while enamel matrix derivative was the most effective at promoting dentin bridge formation. However, further studies with extended follow-up are needed to determine the safe clinical indications for these alternative pulpotomy agents in primary teeth.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFormocresol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEMD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEnamel matrix derivative\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTurmeric extract\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePGMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePost graduate medical institute\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUHS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUniversity of Health Sciences\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOPD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOutpatient department\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSPSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStatistical package for social sciences\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eZOE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eZinc oxide eugenol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComputed tomography.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study approval was obtained from the University of Health Sciences, Lahore (No: UHS/Education/126/2384). Informed consent was obtained from the parents of the patients and/or their legal guardian(s) prior to inclusion in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used during the present study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present study didn\u0026rsquo;t receive any funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNB \u0026ndash; Conception, investigation, data curation, methodology, project administration, writing-original draft, writing-review \u0026amp; editing. SN \u0026ndash; methodology, supervision, validation and reviewed manuscript. RD \u0026ndash; project administration, validation and reviewed manuscript. \u0026nbsp;SK \u0026ndash; visualization, data analysis, data interpretation and writing-review \u0026amp; editing. MAH \u0026ndash; statistical analysis, data interpretation, writing-original draft, writing-review \u0026amp; editing. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGupta N, Bhat M, Devi P, Girish. Aloe-Vera: A Nature's Gift to Children. Int J Clin Pediatr Dent. 2010;3(2):87\u0026ndash;92.\u003c/li\u003e\n\u003cli\u003eModena KC, Casas-Apayco LC, Atta MT, Costa CA, Hebling J, Sipert CR, Navarro MF, Santos CF. Cytotoxicity and biocompatibility of direct and indirect pulp capping materials. J Appl Oral Sci. 2009;17(6):544\u0026thinsp;\u0026minus;\u0026thinsp;54.\u003c/li\u003e\n\u003cli\u003eWaterhouse PJ, Whitworth JM, Camp JH, Fuks AB. Pediatric endodontics: endodontic treatment for the primary and young permanent dentition. In: Hargreaves KM, Cohen S, editors. Cohen's pathways of the pulp. 10th ed. Mosby; 2011. p. 808\u0026thinsp;\u0026minus;\u0026thinsp;57.\u003c/li\u003e\n\u003cli\u003ePrabhakar AR, Mandroli PS, Bhat K. Pulpotomy with curcumin: Histological comparison with mineral trioxide aggregate in rats. Indian J Dent Res. 2019;30(1):31\u0026thinsp;\u0026minus;\u0026thinsp;6.\u003c/li\u003e\n\u003cli\u003eOliadarani FK, Haghgoo R, Mashhadiabbas F, Kahvand M. Histopathological Evaluation of Dental Pulp of Primary Teeth Pulpotomized with Formocresol with/without a Capping Agent: A Randomized Clinical Trial. J Int Soc Prev Community Dent. 2018;8(5):420-3.\u003c/li\u003e\n\u003cli\u003eSaikiran KV, Kamatham R, Sahiti PS, Nuvvula S. Pulpotomy medicaments in primary teeth: A literature review of natural alternatives. SRM J Res Dent Sci. 2018;9:181.\u003c/li\u003e\n\u003cli\u003eSchmalz G, Widbiller M, Galler KM. Clinical Perspectives of Pulp Regeneration. J Endod. 2020;46(9S):S161-74.\u003c/li\u003e\n\u003cli\u003eNajeeb S, Khurshid Z, Sohail Zafar M, Zohaib S, Siddiqui F. Efficacy of Enamel Matrix Derivative in Vital Pulp Therapy: A Review of Literature. Iran Endod J. 2017;12(3):269\u0026thinsp;\u0026minus;\u0026thinsp;75.\u003c/li\u003e\n\u003cli\u003eSculean A, Schwarz F, Becker J, Brecx M. The application of an enamel matrix protein derivative (Emdogain) in regenerative periodontal therapy: a review. Med Princ Pract. 2007;16(3):167\u0026thinsp;\u0026minus;\u0026thinsp;80.\u003c/li\u003e\n\u003cli\u003eWang Y, Zhao Y, Ge L. Effects of the enamel matrix derivative on the proliferation and odontogenic differentiation of human dental pulp cells. J Dent. 2014;42(1):53\u0026thinsp;\u0026minus;\u0026thinsp;9.\u003c/li\u003e\n\u003cli\u003ePalombo EA. Traditional medicinal plant extracts and natural products with activity against oral bacteria: potential application in the prevention and treatment of oral diseases. Evid Based Complement Alternat Med. 2011;2011:680354.\u003c/li\u003e\n\u003cli\u003eAggarwal BB, Sung B. Pharmacological basis for the role of curcumin in chronic diseases: An age-old spice with modern targets Trends Pharmacol Sci. 2009;30:85\u0026ndash;94.\u003c/li\u003e\n\u003cli\u003eSinjari B, Pizzicannella J, D'Aurora M, Zappacosta R, Gatta V, Fontana A, Trubiani O, Diomede F. Curcumin/liposome nanotechnology as delivery platform for anti-inflammatory activities via NFkB/ERK/pERK pathway in human dental pulp treated with 2-HydroxyEthyl MethAcrylate (HEMA). Front Physiol. 2019;10:633.\u003c/li\u003e\n\u003cli\u003eHugar SM, Kukreja P, Hugar SS, Gokhale N, Assudani H. Comparative evaluation of clinical and radiographic success of formocresol, propolis, turmeric gel, and calcium hydroxide on pulpotomized primary molars: A preliminary study. Int J Clin Pediatr Dent. 2017;10(1):18\u0026ndash;23.\u003c/li\u003e\n\u003cli\u003ePurohit RN, Bhatt M, Purohit K, Acharya J, Kumar R, Garg R. Clinical and radiological evaluation of turmeric powder as a pulpotomy medicament in primary teeth: An in vivo study. Int J Clin Pediatr Dent. 2017;10(1):37\u0026ndash;40.\u003c/li\u003e\n\u003cli\u003eSabbarini 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;34(3):284-7.\u003c/li\u003e\n\u003cli\u003ePrabhakar A, Taur S, Hadakar S, Sugandhan S. Comparison of antibacterial efficacy of calcium hydroxide paste, 2% chlorhexidine gel and turmeric extract as an intracanal medicament and their effect on microhardness of root dentin: An in vitro study. Int J Clin Pediatr Dent. 2013;6(3):171-7.\u003c/li\u003e\n\u003cli\u003eAeinehchi M, Eslami B, Ghanbariha M, Saffar AS. Mineral trioxide aggregate (MTA) and calcium hydroxide as pulp-capping agents in human teeth: a preliminary report. Int Endod J. 2003;36(3):225\u0026thinsp;\u0026minus;\u0026thinsp;31.\u003c/li\u003e\n\u003cli\u003eChacko V, Kurikose S. Human pulpal response to mineral trioxide aggregate (MTA): a histologic study. J Clin Pediatr Dent. 2006;30(3):203-9.\u003c/li\u003e\n\u003cli\u003eNakanishi T, Mukai K, Yumoto H, Hirao K, Hosokawa Y, Matsuo T. Anti-inflammatory effect of catechin on cultured human dental pulp cells affected by bacteria-derived factors. Eur J Oral Sci. 2010;118(2):145\u0026thinsp;\u0026minus;\u0026thinsp;50.\u003c/li\u003e\n\u003cli\u003eJurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev. 2009;14(2):141\u0026thinsp;\u0026minus;\u0026thinsp;53. Erratum in: Altern Med Rev. 2009;14(3):277.\u003c/li\u003e\n\u003cli\u003eZhang B, Xiao M, Cheng X, Bai Y, Chen H, Yu Q, Qiu L. Enamel matrix derivative enhances the odontoblastic differentiation of dental pulp stem cells via activating MAPK signaling pathways. Stem Cells Int. 2022;2022:2236250.\u003c/li\u003e\n\u003cli\u003eNakamura Y, Hammarstr\u0026ouml;m L, Matsumoto K, Lyngstadaas SP. The induction of reparative dentine by enamel proteins. Int Endod J. 2002;35(5):407\u0026thinsp;\u0026minus;\u0026thinsp;17.\u003c/li\u003e\n\u003cli\u003eIgarashi R, Sahara T, Shimizu-Ishiura M, Sasaki T. Porcine enamel matrix derivative enhances the formation of reparative dentine and dentine bridges during wound healing of amputated rat molars. J Electron Microsc (Tokyo). 2003;52(2):227\u0026thinsp;\u0026minus;\u0026thinsp;36.\u003c/li\u003e\n\u003cli\u003eOlsson H, Davies JR, Holst KE, Schr\u0026ouml;der U, Petersson K. Dental pulp capping: effect of Emdogain Gel on experimentally exposed human pulps. Int Endod J. 2005;38(3):186\u0026thinsp;\u0026minus;\u0026thinsp;94.\u003c/li\u003e\n\u003cli\u003eKim SG, Zheng Y, Zhou J, Chen M, Embree MC, Song K, et al. Dentin and dental pulp regeneration by the patient\u0026rsquo;s endogenous cells. Endod Topics. 2013;28:106‑17.\u003c/li\u003e\n\u003cli\u003eGaller KM, Weber M, Korkmaz Y, Widbiller M, Feuerer M. Inflammatory response mechanisms of the dentine‑pulp complex and the periapical tissues. Int J Mol Sci. 2021;22:1480.\u003c/li\u003e\n\u003cli\u003eAguilar P, Linsuwanont P. Vital pulp therapy in vital permanent teeth with cariously exposed pulp: A systematic review. J Endod. 2011;37:581‑7.\u003c/li\u003e\n\u003cli\u003eYamamoto H, Hanada K, Kawasaki K, Nishijima M. Inhibitory effect on curcumin on mammalian phospholipase D activity. FEBS Lett. 1997;417(2):196-8.\u003c/li\u003e\n\u003cli\u003eMandrol PS, Bhat K, Prabhakar AR. An in vitro evaluation of cytotoxicity of curcumin against human dental pulp fibroblasts. J Indian Soc Pedod Prev Dent. 2016;34(3):269\u0026thinsp;\u0026minus;\u0026thinsp;72.\u003c/li\u003e\n\u003cli\u003ePanchatcharam M, Miriyala S, Gayathri VS, Suguna L. Curcumin improves wound healing by modulating collagen and decreasing reactive oxygen species. Mol Cell Biochem. 2006;290(1\u0026ndash;2):87\u0026ndash;96.\u003c/li\u003e\n\u003cli\u003eSidhu GS, Singh AK, Thaloor D, Banaudha KK, Patnaik GK, Srimal RC, Maheshwari RK. Enhancement of wound healing by curcumin in animals. Wound Repair Regen. 1998;6(2):167\u0026thinsp;\u0026minus;\u0026thinsp;77.\u003c/li\u003e\n\u003cli\u003eSalman BN, Vahabi S, Rad MM. Use of herbs and medicinal plants in dentistry: a review. J Dent Sch. 2017;35(2):133\u0026thinsp;\u0026minus;\u0026thinsp;49.\u003c/li\u003e\n\u003cli\u003eAsgary S. Micro-computed Tomography Assessment of Full Pulpotomy in a Mature Molar after Five Years: A Case Report. Iran Endod J. 2022;17(4):223-4.\u003c/li\u003e\n\u003cli\u003eGoinka C, Galla PK, Madhavi K, Malempet A, Suryadevara S, Reddy KS. A histopathological comparison of formocresol, propolis, and growth factor as pulpotomy medicaments in primary teeth: An in vivo study. Dent Res J (Isfahan). 2023;20:15.\u003c/li\u003e\n\u003cli\u003ePereira JC, Stanley HR: Pulp capping: influence of the exposure site on pulp healing-histologic and radiographic study in dogs\u0026rsquo; pulp. J Endod. 1981;7:213\u0026thinsp;\u0026minus;\u0026thinsp;23.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Enamel matrix derivative, formocresol, pulpotomy, turmeric extract","lastPublishedDoi":"10.21203/rs.3.rs-5444035/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5444035/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThis study aimed to compare and histologically evaluate the pulpal inflammatory response and dentin bridge formation using Formocresol (FC), Enamel Matrix Derivative (EMD), and Turmeric Extract (TE) as pulpotomy agents in primary teeth.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eEighty-one patients, aged 8\u0026ndash;10 years, requiring both serial extraction and pulpotomy of primary molars were enrolled in this study. One symptomless carious molar tooth from each patient was selected. The participants were divided into three equal groups (n\u0026thinsp;=\u0026thinsp;27 each) based on the time planned for serial extraction: 1 week, 2 weeks, and 6 months. Each group was subdivided into three sub-groups (n\u0026thinsp;=\u0026thinsp;9) according to the pulpotomy agent used (FC, EMD, or TE). Histological evaluations were performed post-extraction to assess pulpal inflammatory response and dentin bridge formation. Statistical analysis was carried out using Fisher\u0026rsquo;s exact test, with a significance threshold set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA statistically significant difference was observed among the three materials regarding pulpal inflammatory response and dentin bridge formation. At 1 week, the FC and EMD groups had moderate inflammation in 88.9% and 77.8% of cases, respectively, while the TE group showed mild inflammation in 55.6% of cases. After 2 weeks, 77.8% of the TE group displayed mild inflammation, 66.7% of the EMD group showed moderate inflammation, and 22.2% of the FC group exhibited severe inflammatory response. By 6 months, 88.9% of the TE group had mild inflammation, while 44.4% of the EMD group showed moderate and 33.3% of the FC group demonstrated severe inflammation. Regarding dentin bridge formation after 6 months, 77.8% of the EMD group exhibited over 75% bridge formation whereas 88.9% of the FC group showed no bridge formation. The TE group showed moderate development with 66.7% showing less than 25% bridge formation.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eTE and EMD demonstrated promising results in this study. Compared to FC, TE showed potential in reducing pulpal inflammation, while EMD was the most effective at promoting dentin bridge formation. However, further studies with extended follow-up are needed to determine the safe clinical indications for these alternative pulpotomy agents in primary teeth.\u003c/p\u003e","manuscriptTitle":"Histological comparison of formocresol, enamel matrix derivative and turmeric extract as pulpotomy agents in primary teeth","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-12 17:21:38","doi":"10.21203/rs.3.rs-5444035/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6df4d3d2-5e7f-478b-96a8-955bbdaf6d85","owner":[],"postedDate":"December 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-20T11:23:39+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-12 17:21:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5444035","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5444035","identity":"rs-5444035","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}