Access the full text.
Sign up today, get DeepDyve free for 14 days.
Loading next page...
/lp/springer-journals/evaluation-of-red-complex-bacteria-loads-in-complete-denture-patients-yNd2epzuTx
- Publisher
- Springer Journals
- Copyright
- Copyright © The Author(s) 2023
- eISSN
- 2056-807X
- DOI
- 10.1038/s41405-023-00133-z
- Publisher site
- See Article on Publisher Site
Abstract
www.nature.com/bdjopen ARTICLE OPEN Evaluation of red-complex bacteria loads in complete denture patients: a pilot study 1 1,2 3 Enis Veseli , Gloria Staka and Marcos Roberto Tovani-Palone © The Author(s) 2023 OBJECTIVE: This pilot study aimed to evaluate red-complex bacteria (RCB) loads in edentulous patients, before and after dentures’ insertion. MATERIALS AND METHODS: Thirty patients were included in the study. Deoxyribonucleic acid (DNA) isolated from bacterial samples were obtained from the dorsum of the tongue before and 3 months after complete dentures (CDs) insertion in order to identify the presence of RCB (Tannerella forsythia, Porphyromonas gingivalis, and Treponema denticola) and quantify their loads, using real-time polymerase chain reaction (RT-PCR). Bacterial loads were represented as “Lg (genome equivalents/sample)” and the data classified according to the “ParodontoScreen” test. RESULTS: Significant changes in bacterial loads were observed before and 3 months after the CDs insertion for: P. gingivalis (0.40 ± 0.90 vs 1.29 ± 1.64, p = 0.0007), T. forsythia (0.36 ±0.94 vs 0.87 ± 1.45, p = 0.005), and T. denticola (0.11 ± 0.41 vs 0.33 ± 0.75, p = 0.03). Before the CDs insertion, all patients had a normal bacterial prevalence range (100%) for all analyzed bacteria. Three months after the insertion, 2 (6.7%) of them had a moderate bacterial prevalence range for P. gingivalis, while 28 (93.3%) had a normal bacterial prevalence range. CONCLUSION: The use of CDs has a significant impact on increasing RCB loads in edentulous patients. BDJ Open (2023) 9:7 ; https://doi.org/10.1038/s41405-023-00133-z INTRODUCTION financial reasons or for the general condition of the patient [9]. Oral flora in edentulous patients is becoming a topic of great With an increasing burden of edentulous elderly people world- interest in dentistry, since dental implants have been increasingly wide, it is expected that there will be an increase in patients used for prosthodontic rehabilitation. Although dental implant seeking treatment with CDs [10]. prosthesis is considered an excellent treatment option for the It is worth noting in this context that polymethylmethacrylate rehabilitation of edentulous patients, its failure can also occur, (PMMA) is a biomaterial considered appropriate and widely used especially due to periimplantitis [1, 2]. Results from different for making CDs [11]. Its unique characteristics make it one of the studies have shown that the microbial component associated with most important materials in the field of dental prosthesis. Despite dental implants failure involves periodontal pathogens that cause this, the use of CDs may modify the oral microbiota, with an inflammation of peri-implant tissues, including red-complex increase in the number of oral pathogens. Overall, most studies in bacteria (RCB)—Tannerella forsythia, Porphyromonas gingivalis, this field have focused on Candida as the main cause of oral and Treponema denticola [3]. Therefore, a rigorous assessment of disorders [12–15], while a much smaller number of studies have periodontal pathogens prior to rehabilitation of edentulous investigated the occurrence of disorders due to periodontal patients should be essential to reduce the chances of failure in pathogens [16, 17]. Among these latter, not all have used the medium and long term. methodologies that provide sufficient evidence of a cause and Initially, it was believed that a full-mouth extraction would lead effect relationship. Yasui et al. [16], analyzed the microbial to the elimination of these pathogens [4]. However, this composition of denture patients with previous rehabilitation, hypothesis has been overturned. With the advancement of comparing these findings with those of patients with natural molecular genetic techniques, researchers have found that teeth. Given that the authors did not conduct any microbial periodontal pathogens are still present in edentulous mouths examination prior to the use of dentures for the first time, their [5–7]. Recent research also suggests that some of these bacteria findings and conclusions do not support the hypothesis of may be involved in the development of various systemic diseases, increased periodontal pathogen loads due to the use of CDs. which can be high risk mainly for the elderly [8]. Here, the present paper attempts to deal with this kind of If, on the one hand, the interest of patients in dental implant inconsistency by presenting a pilot study aiming to add important prostheses has substantially increased nowadays, the demand for insights to the existing research on periodontal pathogens in complete dentures (CDs) remains relatively high, either for denture patients. In light of this, our study was designed to 1 2 Department of Prosthodontics, Dental School, Faculty of Medicine, University of Pristina, Pristina, Kosovo. University Dentistry Clinical Center of Kosovo, Pristina, Kosovo. Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, India. email: enis.veseli@uni-pr.edu Received: 6 December 2022 Revised: 28 January 2023 Accepted: 6 February 2023 1234567890();,: E. Veseli et al. evaluate RCB loads in edentulous patients, before and after about the Parodontoscreen technology is available in detail on the manufacturer’s website [18]. dentures’ insertion. Statistical analysis MATERIALS AND METHODS Series with attributive variables (gender, education, diabetes, smoking, and Ethical approval prevalence of RCB) were analyzed as percentage (%), while numerical The research was approved by the Ethics Board of the University Dentistry series (age, and bacterial load) were described using Descriptive Statistics Clinical Center of the Republic of Kosovo with protocol number 378/2019. (Mean, Standard Deviation (SD); ± 95.00% confidence interval (CI); Mini- Participation in the study was voluntary. All patients were informed about mum; Maximum). The difference in bacterial load values before and the purpose of the study and gave their written consent to participate in it. 3 months after denture use was analyzed using Wilcoxon Matched Pairs Test (Z/p) and Sign Test (Z/p). The Fisher’s exact test (Monte Carlo two- sided p values) was performed to analyze the discrepancies between the Study participants attribution series. All p values < 0.05 were considered significant. The present pilot study was carried out from September 2021 to February 2022 at the Department of Prosthodontics at the University Dental Clinical Center in Pristina, Republic of Kosovo. A total of thirty patients who were RESULTS treated with CDs participated in the study. Inclusion criteria were as Study population follows: (1) fully edentulous dental arches; (2) healthy oral mucosa (without inflammatory changes or any oral pathology). Exclusion criteria were: (1) Thirty edentulous patients were treated with conventional high alveolar bone loss; (2) use of immunosuppressants; (3) brain disorders removable CDs in both jaws. The patient group included 17 in old age; (4) previous use of CDs; (5) antibiotic therapy in the last (56.7%) men and 13 (43.3%) women. The distribution of other 3 months. demographic parameters is shown in Table 1. CDs were made with PMMA material by using the heat curing technique. Patients were instructed to remove the dentures for 8 h a day (during the Microbiological examination night sleep), as well as to clean them. The frequency of periodontal pathogens before and after dentures’ insertion is shown in Fig. 2. The frequency of RCB in Microbiological examination our samples before the CDs insertion was as follows: Porphyr- Microbiological data were analyzed before and 3 months after CDs omonas gingivalis was identified in 6 (20%) samples, Tannerella insertion. The samples were taken from the dorsum of the tongue with a forsythia in 4 (13.3%), and Treponema denticola in 2 (6.6%). After swab, which was rubbed several times for 45 s on a surface (dorsum of the 3 months of the CDs insertion, we observed that the frequency of tongue) of 1 cm . The samples were obtained in the morning before RCB increased considerably, with P. gingivalis being detected in 15 eating. Each sample was then placed in a sterile container containing 2 ml (50%) of the samples, T. forsythia in 10 (33.3%), and T. denticola in of 0.9% sodium chloride saline solution and later (within a short time) sent to the microbiology laboratory. Laboratory procedures included four steps: 6 (20%). separation of the sample from the swab, isolation of bacterial deoxyr- The bacterial load values for all RCB are described in Table 2. ibonucleic acid (DNA), detection of bacteria, and interpretation of results. The bacterial load value for P. gingivalis ranged from 0.40 to ±0.90 The detection of the following bacteria: Tannerella forsythia, Porphyromo- Lg; ±95.00% CI: 0.06–0.73; with a minimum value of 0 Lg and a nas gingivalis, and Treponema denticola was performed using the maximum value of 3.70 Lg. After 3 months of the CDs insertion, Parodontoscreen technology via real-time polymerase chain reaction (RT- the bacterial load value for P. gingivalis varied in the range of PCR). This technology enables direct laboratory analysis to be carried out— 1.29 ± 1.64 Lg; ±95.00% CI: 0.67–1.90; while the minimum value thus a biological sample can be analyzed to determine the presence and found was 0 Lg and the maximum value was 5.00 Lg. A significant quantity of DNA from opportunistic microflora. In this sense, it was also increase was observed for the load of all bacteria after 3 months of important to evaluate the sample intake control (SIC) to control the validity of the results through quantifying the human genomic DNA. In this case, if the CDs insertion (p < 0.05) (Table 2). the SIC value is less than 2.5, the sample is considered to contain an insufficient amount of DNA for obtaining a reliable result. Data processing was performed using DTlite1 and DTprime2 REAL-TIME Thermal cyclers devices produced by “DNA-Technology”. The results were classified based Table 1. Study population demographics. on a test report previously prepared by the manufacturer (Fig. 1). Bacterial load values were determined for each periodontal pathogen using the lg n = 30 unit (logarithm of the number of genomes per sample). More information Gender n (%) Male 17 (56.7%) Female 13 (43.3%) Age (years) Mean ± SD 65.33 ± 6.58 Range 57–82 Diabetes, n (%) Yes 16 (53.3%) No 14 (46.7%) Smokers, n (%) Yes 8 (26.7%) No 22 (73.3 %) Education, n (%) Primary 10 (33.3%) Secondary 18 (60.0%) High 2 (6.7%) Fig. 1 ParodontoScreen test report form. Interpretation of RT-PCR results for each RCB microorganism based on the ParodontoScreen test. SD standard deviation. BDJ Open (2023) 9:7 E. Veseli et al. using DNA extraction and analysis methods detected the presence of periodontal pathogens in edentulous patients. These studies clearly show the importance of molecular genetic methods for the detection of periodontal pathogens, providing robust evidence that such pathogens are able to colonize the oral cavity even in edentulous patients. We also found in the present study a significant increase in RCB bacterial load after 3 months of the CDs insertion. The greatest increases were found for P. gingivalis, followed by T. forsythia, that are two microorganisms that have a strong relationship with each other [20]. Both bacteria, along with T. denticola, have an important impact on host cells with negative implications for the immune system, which may represent a great risk especially for the elderly [21]. Similar results were also found by Andjekovic et al. [17] who analyzed the bacterial load in the residual alveolar Fig. 2 Distribution of positive samples of RCB before and ridges of edentulous patients using PCR. The authors observed a 3 months after the CDs insertion. P.g. Porphyromonas gingivalis; T.f. Tannerella forsythia; T.d. Treponema denticola. significant increase in the bacterial load of Actinobacillus actinomycetemcomitans, Prevotella intermedia, and T. forsythia after 6 months of dentures insertion. In this case, the greater Table 2. Bacterial load values of periodontal pathogens before and increases found in bacterial load can be attributed to the longer 3 months after of treatment with CDs follow-up time of this study compared to ours. Studies by some other researchers also corroborate our (n= 30) findings. Nair et al. [22]. evaluated bacterial contamination in Before After Z P different periods of use of removable dentures and concluded Porphyromonas that the time of use significantly increases bacterial contamina- gingivalis tion. In contrast, the study by SAL Abdul-Kareem et al. [23]. demonstrated that the total number of microorganisms may Mean ± SD 0.40 ± 0.90 1.29 ± 1.64 3.41 0.0007 decrease after 1 month of CDs insertion in edentulous patients. Range (lg) 0–3.7 0–5.0 These discrepant findings reinforce the need and importance of Tannerella forsythia further research in order to determine new insights into the Mean ± SD 0.36 ± 0.94 0.87 ± 1.45 2.80 0.005 influence of time of use on denture contamination. Range (lg) 0–3.1 0–4.4 Another explanation for the increase in bacterial load observed in our study must be related to the degree of roughness of the Treponema denticola polymethylmethacrylate material used in the making of CDs. This Mean ± SD 0.11 ± 0.41 0.33 ± 0.75 2.20 0.03 is because the presence of pores on the denture surface increases Range (lg) 0–1.8 0–2.8 the possibility of bacterial colonization [24]. It is expected that CDs lg logarithm of the number of genomes, SD standard deviation, Z and P insertion will affect the salivary flow and thus the denture to be statistical variables. covered by a layer called ‘pellicle’, which through specific interactions facilitates the colonization of bacteria, making the denture a source of infection [25]. Another important factor that The results presented in Table 3 show the RCB prevalence can impact bacterial loads is the materials used to make CDs. In before and after CDs insertion. A normal bacterial prevalence the present study, CDs were made by using the conventional heat- range (<5.0 Lg) was found for P. gingivalis before the CDs insertion cured polymer. Arutyunov et al. [26] investigated microbial in the samples from all patients (100.0%). On the other hand, a adhesion to different denture-making techniques using PMMA moderate bacterial prevalence range (>5.0 Lg) for P. gingivalis was and found that the microbial adhesion index for hot-cured found in 2 (6.7%) samples after 3 months of the CDs insertion, polymers was considered average compared to other methods. while in the other 28 (93.3%) a normal range (<5.0 Lg) (Table 3) Although all patients participating in our study received was observed. The results of the Fisher’s exact test (Monte Carlo instructions on appropriate use and hygiene of the prosthesis, two-sided p values), showed constant values. the bacterial load level was found to be high after a short period. One of the possible approaches to prevent bacterial colonization is the use of antimicrobial materials. Brown et al. [27] in their DISCUSSION research concluded that regular use of denture cleaning tablets In the present study, we analyzed samples from the dorsum of the has the best effect in reducing polymicrobial biofilms. Thus, tongue from edentulous patients by means of RT-PCR in two immersion of removable dentures in cleaning solutions may be periods, before and 3 months after CDs insertion. The micro- useful and encouraged to complete denture cleaning. organisms analyzed included the following pathogens: Tannerella Furthermore, based on the patient’s age, health status, and forsythia, Porphyromonas gingivalis, and Treponema denticola. The decline immune system with age, the results of the present colonization by RCB in edentulous patients can be initially study suggest that more importance should be given to all attributed to the morphology of the dorsum of the tongue, which factors associated with bacterial colonization of CDs, given that is rich in papillae and fissures, providing a favorable environment the spread of RCB into the bloodstream may represent an for bacterial colonization. Corroborating our study, Velden et al. increased risk in the development of several systemic diseases [19] found in their research that the dorsum of the tongue can be [8, 28]. a source of infection caused by periodontal pathogens, which is not still a consensus. The results of the experimental study by Limitations, strengths and future directions Danser et al. [4] did not indicate the presence of P. gingivalis after A limitation of the present study is the inclusion of smokers and full-mouth extraction. In contrast to that, our findings are in diabetes patients, as well as the fact that the study was carried out agreement with different previous researches including those by during the coronavirus disease 2019 pandemic. All these Sachdeo et al. [5], Fernandes et al. [6] and Cortelli et al. [7], which conditions have been shown in previous research to have the BDJ Open (2023) 9:7 E. Veseli et al. 10. Peltzer K, Hewlett S, Yawson AE, Moynihan P, Preet R, Wu F, et al. Prevalence of Table 3. Prevalence of periodontal pathogens before and after loss of all teeth (edentulism) and associated factors in older adults in China, 3 months of treatment with CDs. Ghana, India, Mexico, Russia and South Africa. Int J Environ Res Public Health. 2014;11:11308–24. Bacteria prevalence 11. Zafar MS. Prosthodontic applications of polymethyl methacrylate (PMMA): an Before After (n = 30) update. Polym (Basel). 2020;12:2299. 12. Manikandan S, Vinesh E, Selvi DT, Kannan RK, Jayakumar A, Dinakaran J. Pre- Severe Moderate Normal valence of Candida among Denture Wearers and Nondenture Wearers. J Pharm Porphyromonas Normal Count 0 2 28 Bioallied Sci. 2022;14:S702–5. gingivalis 13. Le Bars P, Kouadio AA, Bandiaky ON, Le Guéhennec L, de La Cochetière MF. Host’s % 0.00% 6.70% 93.30% immunity and Candida species associated with denture stomatitis: a narrative Tannerella Normal Count 0 0 30 review. Microorganisms. 2022;10:1437. forsythia 14. Morse DJ, Smith A, Wilson MJ, Marsh L, White L, Posso R, et al. Molecular com- munity profiling of the bacterial microbiota associated with denture-related % 0.00% 0.00% 100.00% stomatitis. Sci Rep. 2019;9:10228. Treponema Normal Count 0 0 30 15. Kinkela Devcic M, Simonic-Kocijan S, Prpic J, Paskovic I, Cabov T, Kovac Z, et al. denticola Oral candidal colonization in patients with different prosthetic appliances. J Fungi % 0.00% 0.00% 100.00% (Basel). 2021;7:662. 16. Yasui M, Ryu M, Sakurai K, Ishihara K. Colonisation of the oral cavity by period- ontopathic bacteria in complete denture wearers. Gerodontology. ability to impact the colonization of microorganisms, which may 2012;29:e494–502. have influenced the results of this study [29–31]. 17. Andjelkovic M, Sojic LT, Lemic AM, Nikolic N, Kannosh IY, Milasin J. Does the Moreover, the evaluation of the loads of other periodontal prevalence of periodontal pathogens change in elderly edentulous patients after pathogens besides the RCB was not conducted, which does not complete denture treatment? J. Prosthodont. 2017;26:364–9. allow extrapolating our results to the entire population of 18. DNA-Technology. ParodontoScreen [Internet]. Online information available at: periodontal pathogens. Fungi, including Candida albicans, were https://dna-technology.com/equipmentpr/pcr-kits-microbiome-composition- also not evaluated, which limits our conclusions about the loads of screening/parodontoscreen. (accessed 21 Oct 2022). these microorganisms in view of their interactions with period- 19. Van der Velden U, Van Winkelhoff AJ, Abbas F, De Graaff J. The habitat of peri- ontal pathogens within the context studied here. However, our odontopathic micro-organisms. J Clin Periodontol. 1986;13:243–8. 20. Zhu W, Lee SW. Surface interactions between two of the main periodontal findings showed important and robust evidence that denture pathogens: Porphyromonas gingivalis and Tannerella forsythia. J. Periodontal treatment in edentulous patients is associated with significant Implant Sci. 2016;46:2–9. changes in the levels of RCB. Finally, we express our opinion that 21. Jun HK, Jung YJ, Choi BK. Treponema denticola, Porphyromonas gingivalis, and the present work provides a new concept for the future of Tannerella forsythia induce cell death and release of endogenous danger signals. implant-prosthetic planning in edentulous patients, especially Arch Oral. Biol. 2017;73:72–8. considering the importance of these bacteria in the development 22. Nair VV, Karibasappa GN, Dodamani A, Prashanth VK. Microbial contamination of of peri-implantitis [3]. removable dental prosthesis at different interval of usage: An in vitro study. J Indian Prosthodont Soc. 2016;16:346–51. 23. Abdul-Kareem SAL. Changes in oral flora of newly edentulous patients, before and after complete dentures insertion. J Bagh Coll Dent. 2012;24:65–69. CONCLUSION 24. Günther E, Kommerein N, Hahnel S. Biofilms on polymeric materials for the The use of CDs in edentulous patients may cause a significant fabrication of removable dentures. Dtsch Zahnärztl Z Int. 2020;2:142–51. increase in RCB loads. In light of this, a continuous follow-up of 25. Hao Y, Huang X, Zhou X, Li M, Ren B, Peng X, et al. Influence of dental oral hygiene in edentulous patients is needed, including especially prosthesis and restorative materials interface on oral biofilms. Int J Mol Sci. the cleaning of dentures and tongue, given that both are 2018;19:3157. important sources of periodontal pathogens. The role of cleanli- 26. Arutyunov S, Kirakosyan L, Dubova L, Kharakh Y, Malginov N, Akhmedov G, et al. ness in this case is essential to prevent not only oral health Microbial adhesion to dental polymers for conventional, computer-aided sub- problems, but also the occurrence of systemic disorders. tractive and additive manufacturing: a comparative in vitro study. J Funct Bio- mater. 2022;13:42. 27. Brown JL, Young T, McKloud E, Butcher MC, Bradshaw D, Pratten JR, et al. An in vitro evaluation of denture cleansing regimens against a polymicrobial denture REFERENCES biofilm model. Antibiotics (Basel). 2022;11:113. 1. Gowd MS, Shankar T, Ranjan R, Singh A. Prosthetic consideration in implant- 28. Malinowski B, Węsierska A, Zalewska K, Sokołowska MM, Bursiewicz W, Socha M, supported prosthesis: a review of literature. J Int Soc Prev Community Dent. et al. The role of Tannerella forsythia and Porphyromonas gingivalis in patho- 2017;7:S1–7. genesis of esophageal cancer. Infect Agent Cancer. 2019;14:3. 2. Valente NA, Andreana S. Peri-implant disease: what we know and what we need 29. Jiang Y, Zhou X, Cheng L, Li M. The impact of smoking on subgingival microflora: to know. J Periodontal Implant Sci. 2016;46:136–51. from periodontal health to disease. Front Microbiol. 2020;11:66. 3. Al-Ahmad A, Muzafferiy F, Anderson AC, Wölber JP, Ratka-Krüger P, Fretwurst T, 30. Ali T, Rumnaz A, Urmi UL, Nahar S, Rana M, Sultana F, et al. Type-2 diabetes et al. Shift of microbial composition of peri-implantitis-associated oral biofilm as mellitus individuals carry different periodontal bacteria. Pesqui Bras Odontope- revealed by 16S rRNA gene cloning. J Med Microbiol. 2018;67:332–40. diatria Clin Integr. 2021;21:e0107. 4. Danser MM, van Winkelhoff AJ, de Graaff J, Loos BG, van der Velden U. Short-term 31. Karimzadeh F, Sajedi SM, Taram S, Karimzadeh F. Comparative evaluation of effect of full-mouth extraction on periodontal pathogens colonizing the oral bacterial colonization on removable dental prostheses in patients with COVID-19: mucous membranes. J Clin Periodontol. 1994;21:484–9. A clinical study. J Prosthet Dent. 2021;S0022-3913:00252–3. 5. Sachdeo A, Haffajee AD, Socransky SS. Biofilms in the edentulous oral cavity. J Prosthodont. 2008;17:348–56. 6. Fernandes CB, Aquino DR, Franco GC, Cortelli SC, Costa FO, Cortelli JR. Do elderly edentulous patients with a history of periodontitis harbor periodontal patho- ACKNOWLEDGEMENTS gens? Tex Dent J. 2012;129:751–61. We would like to acknowledge all patients who participated in the study for their 7. Cortelli JR, Aquino DR, Cortelli SC, Nobre Franco GC, Fernandes CB, Roman-Torres cooperation and understanding of the research procedures. CV, et al. Detection of periodontal pathogens in oral mucous membranes of edentulous individuals. J Periodontol. 2008;79:1962–5. 8. Bui FQ, Almeida-da-Silva CLC, Huynh B, Trinh A, Liu J, Woodward J, et al. Asso- ciation between periodontal pathogens and systemic disease. Biomed J. AUTHOR CONTRIBUTIONS 2019;42:27–35. EV and GS: conception and design of the study, acquisition and analysis of data, and 9. Melton AB. Current trends in removable prosthodontics. J Am Dent Assoc. drafting of the paper. Final and critical review and manuscript writing/editing was 2000;131:52S–56S. made by Marcos Roberto Tovani-Palone. BDJ Open (2023) 9:7 E. Veseli et al. COMPETING INTERESTS Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims The authors declare no competing interests. in published maps and institutional affiliations. ETHICS Open Access This article is licensed under a Creative Commons The study was conducted according to the guidelines of the Declaration of Helsinki Attribution 4.0 International License, which permits use, sharing, and approved by the Ethics Board of the University Dentistry Clinical Center of the adaptation, distribution and reproduction in any medium or format, as long as you give Republic of Kosovo (no. 378/ 19, 23 December 2019). appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless INFORMED CONSENT indicated otherwise in a credit line to the material. If material is not included in the Informed consent was obtained from all subjects included in the study. article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http:// ADDITIONAL INFORMATION creativecommons.org/licenses/by/4.0/. Correspondence and requests for materials should be addressed to Enis Veseli. © The Author(s) 2023 Reprints and permission information is available at http://www.nature.com/ reprints BDJ Open (2023) 9:7
Journal
BDJ Open – Springer Journals
Published: Feb 18, 2023