{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T03:42:48Z","timestamp":1771040568393,"version":"3.50.1"},"reference-count":118,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dentistry Journal"],"abstract":"<jats:p>Background: Recent advances in mRNA vaccine technology, accelerated by the global COVID-19 pandemic, have generated significant interest in their applications beyond infectious diseases. Dentistry has emerged as a promising field for exploring the potential of mRNA-based therapies in preventing and treating oral diseases. Objectives: This narrative review aims to evaluate the current status of mRNA vaccine development and its preclinical applications in oral health, focusing on periodontal disease, dental caries, regenerative medicine, implantology, and oral cancer. Methods: The review synthesizes findings from preclinical studies, including research conducted in animal models and in vitro, to assess the potential of mRNA-based therapies to modulate immune responses and promote tissue regeneration in the oral cavity. Clinical trials were only mentioned in the context of broader areas of mRNA vaccine implementation such as oncology and immunotherapy. Results: The preclinical studies highlight the capacity of mRNA vaccines to enhance the body\u2019s immune response and facilitate tissue repair processes. Despite these promising results, challenges persist in delivering mRNA vaccines effectively within the complex oral environment. These challenges include vaccine stability, delivery mechanisms, and the modulation of immune responses. Conclusions: While mRNA vaccines offer significant promise for revolutionizing oral health care, they face notable limitations concerning safety, efficacy, and clinical feasibility. Overcoming these obstacles through further research is essential to unlock their full translational potential and ensure their safe and effective integration into dental practice.<\/jats:p>","DOI":"10.3390\/dj13020079","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T08:01:19Z","timestamp":1739433679000},"page":"79","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Revolutionizing Dentistry: Preclinical Insights and Future Applications of mRNA Vaccines in Dentistry\u2014A Narrative Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1994-3511","authenticated-orcid":false,"given":"Luciana","family":"Koren","sequence":"first","affiliation":[{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7586-1624","authenticated-orcid":false,"given":"Andro","family":"Koren","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Liki\u0107","sequence":"additional","affiliation":[{"name":"Unit for Clinical Pharmacology, Department of Internal Medicine, Clinical Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomislav","family":"Katanec","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, School of Dental Medicine Zagreb, Clinical Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1146\/annurev-med-042420-112725","article-title":"mRNA Vaccines in the COVID-19 Pandemic and Beyond","volume":"73","author":"Hogan","year":"2022","journal-title":"Annu. Rev. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12943-021-01311-z","article-title":"mRNA vaccine: A potential therapeutic strategy","volume":"20","author":"Wang","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103182","DOI":"10.1016\/j.copbio.2024.103182","article-title":"Delivery approaches of immunomodulatory nucleic acids for cancer therapy","volume":"89","author":"Hu","year":"2024","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115162","DOI":"10.1016\/j.addr.2023.115162","article-title":"Preface: A new era of RNA-based therapies","volume":"205","author":"Miyata","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"115175","DOI":"10.1016\/j.addr.2023.115175","article-title":"The immunostimulatory nature of mRNA lipid nanoparticles","volume":"205","author":"Sharma","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Silver, N., Garg, R., Mendez-Gomez, H., Castillo, P., Souza, C., Fagman, L., Ligon, J., Qdaisat, S., Weidert, F., and Chardon-Robles, J. (2022, January 8\u201312). 1383 Remodeling host immune response in head and neck cancer with personalized therapeutic mRNA nano-vaccines. In Proceeding of the SITC 37th Annual Meeting (SITC 2022) Abstracts, Boston, MA, USA.","DOI":"10.1136\/jitc-2022-SITC2022.1383"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"K\u00f6n\u00f6nen, E., and Kumar, P.S. (2015). Bacteriology of periodontal diseases. Molecular Medical Microbiology, Academic Press.","DOI":"10.1016\/B978-0-12-397169-2.00053-6"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Alghamdi, H.S. (2018). Methods to improve osseointegration of dental implants in low quality (type-IV) bone: An overview. J. Funct. Biomater., 9.","DOI":"10.3390\/jfb9010007"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"127526","DOI":"10.1016\/j.micres.2023.127526","article-title":"New strategies and mechanisms for targeting Streptococcus mutans biofilm formation to prevent dental caries: A review","volume":"278","author":"Gao","year":"2023","journal-title":"Microbiol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"19550","DOI":"10.1021\/acsnano.3c05635","article-title":"mRNA Cancer Vaccines: Construction and Boosting Strategies","volume":"17","author":"Liu","year":"2023","journal-title":"ACS Nano"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kurita-Ochiai, T., Hashizume-Takizawa, T., Kobayashi, R., and Yamamoto, M. (2020). Mucosal Vaccines for Oral Disease. Mucosal Vaccines, Elsevier.","DOI":"10.1016\/B978-0-12-811924-2.00037-7"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1186\/s12951-024-02488-3","article-title":"Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection","volume":"22","author":"Zhang","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrd.2017.243","article-title":"mRNA vaccines\u2014A new era in vaccinology","volume":"17","author":"Pardi","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"960","DOI":"10.2174\/1389201014666131226144339","article-title":"Dental caries and vaccination strategy against the major cariogenic pathogen, Streptococcus mutans","volume":"14","author":"Zhang","year":"2013","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ferrer, M.D., P\u00e9rez, S., Lopez, A.L., Sanz, J.L., Melo, M., Llena, C., and Mira, A. (2021). Evaluation of clinical, biochemical and microbiological markers related to dental caries. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18116049"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106282","DOI":"10.1016\/j.oraloncology.2022.106282","article-title":"Personalized mRNA cancer vaccines with immune checkpoint inhibitors: A promising therapeutic approach in oral cancer patients","volume":"137","author":"Gheena","year":"2023","journal-title":"Oral Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1089\/hum.2020.137","article-title":"Treating cystic fibrosis with mRNA and CRISPR","volume":"31","author":"Sanchez","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chen, Y., Jiang, N., Chen, M., Sui, B., and Liu, X. (2022). Identification of tumor antigens and immune subtypes in head and neck squamous cell carcinoma for mRNA vaccine development. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.1064754"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ghosh, S., Shah, P.A., and Johnson, F.M. (2022). Novel systemic treatment modalities including immunotherapy and molecular targeted therapy for recurrent and metastatic head and neck squamous cell carcinoma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147889"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, A., Ji, Q., Sheng, X., and Wu, H. (2023). mRNA vaccine in gastrointestinal tumors: Immunomodulatory effects and immunotherapy. Biomed. Pharmacother., 166.","DOI":"10.1016\/j.biopha.2023.115361"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.jconrel.2024.03.056","article-title":"mRNA therapies: Pioneering a new era in rare genetic disease treatment","volume":"369","author":"Shen","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115190","DOI":"10.1016\/j.addr.2024.115190","article-title":"mRNA delivery systems for cancer immunotherapy: Lipid nanoparticles and beyond","volume":"206","author":"Senti","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1111\/trf.16672","article-title":"Severe Autoimmune Hemolytic Anemia Following Receipt of SARS-CoV-2 mRNA Vaccine","volume":"61","author":"Gadi","year":"2021","journal-title":"Transfusion"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2001812","DOI":"10.1002\/adhm.202001812","article-title":"Next-Generation Vaccines: Nanoparticle-Mediated DNA and mRNA Delivery","volume":"10","author":"Ho","year":"2021","journal-title":"Adv. Healthc. Mater."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"001196","DOI":"10.1099\/mic.0.001196","article-title":"Lactobacilli and human dental caries: More than mechanical retention","volume":"168","author":"Wen","year":"2022","journal-title":"Microbiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.ymthe.2022.11.017","article-title":"Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting","volume":"31","author":"Anttila","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kim, T.J., Kim, Y.G., Jung, W., Jang, S., Ko, H.G., Park, C.H., Byun, J.S., and Kim, D.Y. (2023). Non-Coding RNAs as Potential Targets for Diagnosis and Treatment of Oral Lichen Planus: A Narrative Review. Biomolecules, 13.","DOI":"10.3390\/biom13111646"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1146\/annurev-pharmtox-030320-092348","article-title":"Oral Biologic Delivery: Advances Toward Oral Subunit, DNA, and mRNA Vaccines and the Potential for Mass Vaccination During Pandemics","volume":"61","author":"Coffey","year":"2021","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/978-3-319-42934-2_5","article-title":"mRNA cancer vaccines","volume":"209","author":"Fiedler","year":"2016","journal-title":"Curr. Strateg. Cancer Gene Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"102388","DOI":"10.1016\/j.coi.2023.102388","article-title":"Challenges and opportunities in the development of mucosal mRNA vaccines","volume":"85","author":"Kirtane","year":"2023","journal-title":"Curr. Opin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Adil, S.M., Bhowmik, R., Al-Abbasi, F.A., AlGhamdi, S.A., Alghamdi, A.M., Sarkar, A., Kazmi, I., and Karmakar, S. (2023). Vaccine Formulation Strategies and Challenges Involved in RNA Delivery for Modulating Biomarkers of Cardiovascular Diseases: A Race from Laboratory to Market. Vaccines, 11.","DOI":"10.3390\/vaccines11020241"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"121","DOI":"10.5466\/ijoms.12.121","article-title":"Comparison of Mucosal Immune Response After Oral, Nasal or Sublingual Immunization With an Outer Membrane Protein of Porphyromonas Gingivalis","volume":"12","author":"Ikeda","year":"2013","journal-title":"Int. J. Oral-Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1177\/00220345221084205","article-title":"The impact of mRNA technology in regenerative therapy: Lessons for oral tissue regeneration","volume":"101","author":"Wisitrasameewong","year":"2022","journal-title":"J. Dent. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","article-title":"Lipid nanoparticles for mRNA delivery","volume":"6","author":"Hou","year":"2021","journal-title":"Nat. Rev. Mater."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1016\/j.vaccine.2021.03.038","article-title":"mRNA vaccines manufacturing: Challenges and bottlenecks","volume":"39","author":"Rosa","year":"2021","journal-title":"Vaccine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"114002","DOI":"10.1016\/j.addr.2021.114002","article-title":"mRNA\u2014A game changer in regenerative medicine, cell-based therapy and reprogramming strategies","volume":"179","author":"Chabanovska","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Knezevic, I., Liu, M.A., Peden, K., Zhou, T., and Kang, H.-N. (2021). Development of mRNA vaccines: Scientific and regulatory issues. Vaccines, 9.","DOI":"10.3390\/vaccines9020081"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10732748241238629","DOI":"10.1177\/10732748241238629","article-title":"Advancements in mRNA Vaccines: A Promising Approach for Combating Human Papillomavirus-Related Cancers","volume":"31","author":"Iqbal","year":"2024","journal-title":"Cancer Control"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"D\u00f6rrie, J., Schaft, N., Schuler, G., and Schuler-Thurner, B. (2020). Therapeutic cancer vaccination with ex vivo RNA-transfected dendritic cells\u2014An update. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020092"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Li, H.-X., Liu, T.-R., Tu, Z.-X., Xie, C.-B., Wen, W.-P., and Sun, W. (2022). Screening of tumor antigens and construction of immune subtypes for mRNA vaccine development in head and neck squamous cell carcinoma. Biomolecules, 13.","DOI":"10.3390\/biom13010090"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"103679","DOI":"10.1016\/j.critrevonc.2022.103679","article-title":"Immunotherapy for head and neck cancer: Present and future","volume":"174","author":"Fasano","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1016\/j.apsb.2022.03.011","article-title":"mRNA cancer vaccines: Advances, trends and challenges","volume":"12","author":"He","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1039\/D1BM01454D","article-title":"Optimization of phospholipid chemistry for improved lipid nanoparticle (LNP) delivery of messenger RNA (mRNA)","volume":"10","author":"Farbiak","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.4049\/jimmunol.165.9.4778","article-title":"Cutting Edge: The Mucosal Adjuvant Cholera Toxin Redirects Vaccine Proteins Into Olfactory Tissues","volume":"165","author":"Jackson","year":"2000","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nri2173","article-title":"Dendritic-cell immunotherapy: From ex vivo loading to in vivo targeting","volume":"7","author":"Tacken","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20210146","DOI":"10.1002\/EXP.20210146","article-title":"From structural design to delivery: mRNA therapeutics for cancer immunotherapy","volume":"4","author":"Zhou","year":"2023","journal-title":"Exploration"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jcis.2020.05.002","article-title":"Toxicity and cellular uptake of lipid nanoparticles of different structure and composition","volume":"576","author":"Strachan","year":"2020","journal-title":"J. Colloid Interface Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1166\/jnn.2016.11667","article-title":"Development and evaluation of lipid nanoparticles for drug delivery: Study of toxicity in vitro and in vivo","volume":"16","author":"Winter","year":"2016","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_49","first-page":"486","article-title":"A lipid nanoparticle platform incorporating trehalose glycolipid for exceptional mRNA vaccine safety","volume":"38","author":"Bae","year":"2024","journal-title":"Bioact. Mater."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12967-024-06033-6","article-title":"mRNA vaccines in the context of cancer treatment: From concept to application","volume":"23","author":"Fu","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2404830","DOI":"10.1002\/adma.202404830","article-title":"pH-Responsive \u03b2-Glucans-Complexed mRNA in LNPs as an Oral Vaccine for Enhancing Cancer Immunotherapy","volume":"36","author":"Luo","year":"2024","journal-title":"Adv. Mater."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Lin, Y., Chen, X., Wang, K., Liang, L., and Zhang, H. (2024). An overview of nanoparticle-based delivery platforms for mRNA vaccines for treating cancer. Vaccines, 12.","DOI":"10.3390\/vaccines12070727"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100267","DOI":"10.1016\/j.iotech.2022.100267","article-title":"155P BNT113 + Pembrolizumab as Firstline Treatment in Patients with Unresectable Recurrent\/Metastatic HNSCC: Preliminary Safety Data from AHEAD-MERIT","volume":"16","author":"Klinghammer","year":"2022","journal-title":"Immuno-Oncol. Technol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.jhep.2021.08.011","article-title":"Therapeutic HNF4A mRNA attenuates liver fibrosis in a preclinical model","volume":"75","author":"Yang","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Inagaki, M. (2023). Cell Reprogramming and Differentiation Utilizing Messenger RNA for Regenerative Medicine. J. Dev. Biol., 12.","DOI":"10.20944\/preprints202311.0233.v1"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Wang, A.Y.L. (2021). Application of Modified mRNA in Somatic Reprogramming to Pluripotency and Directed Conversion of Cell Fate. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158148"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7274","DOI":"10.1111\/febs.16162","article-title":"Current status and future directions of clinical applications using iPS cells-focus on Japan","volume":"289","author":"Tsujimoto","year":"2022","journal-title":"FEBS J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41536-023-00317-z","article-title":"Transgene-free direct conversion of murine fibroblasts into functional muscle stem cells","volume":"8","author":"Qabrati","year":"2023","journal-title":"NPJ Regen. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"C107","DOI":"10.1152\/ajpcell.00504.2023","article-title":"Emerging mRNA therapies for cardiac fibrosis","volume":"326","author":"Jardin","year":"2024","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1002\/jbm.a.37076","article-title":"Bone Marrow Coagulated and Low-Level Laser Therapy Accelerate Bone Healing by Enhancing Angiogenesis, Cell Proliferation, Osteoblast Differentiation, and Mineralization","volume":"109","author":"Santinoni","year":"2021","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1172\/JCI82585","article-title":"Osteoblast-derived VEGF regulates osteoblast differentiation and bone formation during bone repair","volume":"126","author":"Hu","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1016\/j.cell.2015.05.029","article-title":"Glucose uptake and runx2 synergize to orchestrate osteoblast differentiation and bone formation","volume":"161","author":"Kajimura","year":"2015","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s41232-023-00285-3","article-title":"Enhancement of bone regeneration by coadministration of angiogenic and osteogenic factors using messenger RNA","volume":"43","author":"Zhang","year":"2023","journal-title":"Inflamm. Regen."},{"key":"ref_65","first-page":"763","article-title":"Hypoxia Mediates Runt-Related Transcription Factor 2 Expression via Induction of Vascular Endothelial Growth Factor in Periodontal Ligament Stem Cells","volume":"42","author":"Xu","year":"2019","journal-title":"Mol. Cells"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Tsou, H.-K., Wu, C.-H., Chan, L.Y., Kataoka, K., Itokazu, N., Tsuzuki, M., Hu, H., Zhuo, G.-Y., Itaka, K., and Lin, C.-Y. (2023). Administration of mRNA-Nanomedicine-Augmented Calvarial Defect Healing via Endochondral Ossification. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071965"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jconrel.2022.11.022","article-title":"Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines","volume":"353","author":"Kim","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_68","first-page":"220","article-title":"The novelty of mRNA viral vaccines and potential harms: A scoping review","volume":"6","author":"Halma","year":"2023","journal-title":"J"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1038\/s41598-018-19742-y","article-title":"Evaluation of the osteogenesis and osseointegration of titanium alloys coated with graphene: An in vivo study","volume":"8","author":"Li","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"354","DOI":"10.3390\/ijms11010354","article-title":"Surface modification of biomedical and dental implants and the processes of inflammation, wound healing and bone formation","volume":"11","author":"Stanford","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.actbio.2023.03.031","article-title":"The immunomodulatory effects of RNA-based biomaterials on bone regeneration","volume":"162","author":"Wang","year":"2023","journal-title":"Acta Biomater."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s42003-020-01606-9","article-title":"BMP-2 and VEGF-A modRNAs in collagen scaffold synergistically drive bone repair through osteogenic and angiogenic pathways","volume":"4","author":"Geng","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wang, Z., Zhang, J., Hu, J., and Yang, G. (2022). Gene-activated titanium implants for gene delivery to enhance osseointegration. Biomater. Adv., 143.","DOI":"10.1016\/j.bioadv.2022.213176"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/jre.12718","article-title":"Long non-coding RNA and mRNA expression profiles in peri-implantitis vs periodontitis","volume":"55","author":"Liu","year":"2019","journal-title":"J. Periodontal Res."},{"key":"ref_75","first-page":"891","article-title":"mRNA encoding BMP-2 enhances osteogenesis in periodontal ligament stem cells and holds potential for improving dental implant integration","volume":"50","author":"Liu","year":"2023","journal-title":"J. Clin. Periodontol."},{"key":"ref_76","first-page":"212","article-title":"mRNA vaccines encoding BMP-2 accelerate healing and improve implant stability in a rat model of dental implants","volume":"20","author":"Zhou","year":"2021","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Song, Y., Mehl, F., and Zeichner, S.L. (2024). Vaccine Strategies to Elicit Mucosal Immunity. Vaccines, 12.","DOI":"10.3390\/vaccines12020191"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ongun, M., Lokras, A.G., Baghel, S., Shi, Z., Schmidt, S.T., Franzyk, H., Rades, T., Sebastiani, F., Thakur, A., and Foged, C. (2024). Lipid nanoparticles for local delivery of mRNA to the respiratory tract: Effect of PEG-lipid content and administration route. Eur. J. Pharm. Biopharm., 198.","DOI":"10.1016\/j.ejpb.2024.114266"},{"key":"ref_79","unstructured":"Gore, D., Kanase, S., Bhor, D., Pawar, T., Kale, S., Deokar, A., and Shinde, V. (2024). A Detailed Review of Emerging Therapy for Oral Health. Int. J. Sci. R. Tech., 264\u2013274."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2306081","DOI":"10.1002\/adma.202306081","article-title":"Oral nanomedicine: Challenges and opportunities","volume":"36","author":"Deng","year":"2024","journal-title":"Adv. Mater."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476286.2024.2333123","article-title":"mRNA vaccine designs for optimal adjuvanticity and delivery","volume":"21","author":"Mochida","year":"2024","journal-title":"RNA Biol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Rezaei, T., Mehramouz, B., Gholizadeh, P., Yousefi, L., Ganbarov, K., Ghotaslou, R., Taghizadeh, S., and Kafil, H.S. (2023). Factors associated with Streptococcus mutans pathogenicity in the oral cavity. Biointerface Res. Appl. Chem., 13.","DOI":"10.33263\/BRIAC134.368"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/omi.12152","article-title":"Advances in the microbial etiology and pathogenesis of early childhood caries","volume":"32","author":"Hajishengallis","year":"2017","journal-title":"Mol. Oral Microbiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e2400271","DOI":"10.1002\/jobm.202400271","article-title":"Advancing Anti-Biofilm Strategies: Innovations to Combat Biofilm-Related Challenges and Enhance Efficacy","volume":"64","author":"Javanmard","year":"2024","journal-title":"J. Basic Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Pangabam, B.D., Naorem, R.S., Teli, A.B., and Fekete, C. (2024, October 27). Immunoinformatics-Driven Multiepitope Vaccine Targeting Streptococcus mutans for Dental Caries Prevention. 2023, PPR700749. Research Square. Available online: https:\/\/www.researchsquare.com\/article\/rs-3214083\/v1.","DOI":"10.21203\/rs.3.rs-3214083\/v1"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"9365845","DOI":"10.1155\/2023\/9365845","article-title":"Dental Caries and Its Management","volume":"2023","author":"Warreth","year":"2023","journal-title":"Int. J. Dent."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1574-6968.2006.00378.x","article-title":"Treatment of Streptococcus mutans with antisense oligodeoxyribonucleotides to gtfB mRNA inhibits GtfB expression and function","volume":"264","author":"Guo","year":"2006","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Mao, M.Y. (2016). The rnc gene promotes exopolysaccharide synthesis and represses the vicRKX gene expressions via microRNA-size small RNAs in Streptococcus mutans. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00687"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Yu, S., Xu, M., Wang, Z., Deng, Y., Xu, H.H.K., Weir, M.D., Homayounfar, N., Fay, G.G., Chen, H., and Yang, D. (2024). S. mutans Antisense vicK RNA Over-Expression Plus Antibacterial Dimethylaminohexadecyl Methacrylate Suppresses Oral Biofilms and Protects Enamel Hardness in Extracted Human Teeth. Pathogens, 13.","DOI":"10.3390\/pathogens13080707"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"55","DOI":"10.5539\/ijb.v5n4p55","article-title":"Dental caries: The most common disease worldwide and preventive strategies","volume":"5","author":"Ozdemir","year":"2013","journal-title":"Int. J. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Han, J., and Poma, A. (2022). Molecular targets for antibody-based anti-biofilm therapy in infective endocarditis. Polymers, 14.","DOI":"10.3390\/polym14153198"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"34","DOI":"10.4103\/jioh.jioh_220_22","article-title":"Anticaries vaccine as a promising alternative for protection against dental caries: A literature review","volume":"15","author":"Contreras","year":"2023","journal-title":"J. Int. Oral Health"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.dental.2019.12.001","article-title":"Effects of S. mutans Gene-Modification and Antibacterial Monomer Dimethylaminohexadecyl Methacrylate on Biofilm Growth and Acid Production","volume":"36","author":"Chen","year":"2020","journal-title":"Dent. Mater."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Nabeel, M., Nisath, S.M.R., Reddy, M.H., Rohan Vignesh, S., and Joshi, A. (2024). Advancing Oral Healthcare: Ai-Driven Caries Detection and Nanomaterial-Enhanced Treatment. SSRN Electron. J., accepted.","DOI":"10.2139\/ssrn.5076026"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1186\/s12951-024-02901-x","article-title":"Nanotechnology in healthcare, and its safety and environmental risks","volume":"22","author":"Ma","year":"2024","journal-title":"J. Nanobiotechnology"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Franco, C., Patricia, H.R., Timo, S., Claudia, B., and Marcela, H. (2017). Matrix metalloproteinases as regulators of periodontal inflammation. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020440"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"64","DOI":"10.4103\/0972-124X.55837","article-title":"Anticytokine therapy for periodontal diseases: Where are we now?","volume":"13","author":"Waykole","year":"2009","journal-title":"J. Indian Soc. Periodontol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"112650","DOI":"10.1016\/j.intimp.2024.112650","article-title":"Advances and challenges in the development of periodontitis vaccines: A comprehensive review","volume":"140","author":"Liao","year":"2024","journal-title":"Int Immunopharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"98","DOI":"10.37231\/ajmb.2024.8.2.761","article-title":"Overview of Gram-negative anaerobic pathogens associated with periodontal disease: A review","volume":"8","author":"Yusoff","year":"2024","journal-title":"Asian J. Med. Biomed."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Wang, Y., Xue, N., Wang, Z., Zeng, X., Ji, N., and Chen, Q. (2023). Targeting Th17 cells: A promising strategy to treat oral mucosal inflammatory diseases. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1236856"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Belibasakis, G.N., Belstr\u00f8m, D., Eick, S., Gursoy, U.K., Johansson, A., and K\u00f6n\u00f6nen, E. (2023). Periodontal Microbiology and Microbial Etiology of Periodontal Diseases: Historical Concepts and Contemporary Perspectives. Periodontol. 2000.","DOI":"10.1111\/prd.12473"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Vaernewyck, V., Arzi, B., Sanders, N.N., Cox, E., and Devriendt, B. (2021). Mucosal Vaccination Against Periodontal Disease: Current Status and Opportunities. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.768397"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1600-0757.2012.00457.x","article-title":"Risk factors for periodontal disease","volume":"62","author":"Genco","year":"2013","journal-title":"Periodontol. 2000"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/prd.12297","article-title":"The role of inflammation and genetics in periodontal disease","volume":"83","author":"Loos","year":"2020","journal-title":"Periodontol. 2000"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00011-020-01418-x","article-title":"Impaired Salivary SIgA Antibodies Elicit Oral Dysbiosis and Subsequent Induction of Alveolar Bone Loss","volume":"70","author":"Chang","year":"2020","journal-title":"Inflamm. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/s12276-023-00999-x","article-title":"Knife\u2019s edge: Balancing immunogenicity and reactogenicity in mRNA vaccines","volume":"55","author":"Lee","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Cugini, C., Ramasubbu, N., Tsiagbe, V.K., and Fine, D.H. (2021). Dysbiosis from a microbial and host perspective relative to oral health and disease. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.617485"},{"key":"ref_108","unstructured":"Verschoren, J. (2023). Development of a Buccal Self-Amplifying mRNA Vaccine for Periodontal Disease Prophylaxis in Dogs: Preliminary Testing. [Ph.D. Thesis, Ghent University]."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41586-023-06127-z","article-title":"Algorithm for optimized mRNA design improves stability and immunogenicity","volume":"621","author":"Zhang","year":"2023","journal-title":"Nature"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41577-021-00583-2","article-title":"Mucosal vaccines\u2014Fortifying the frontiers","volume":"22","author":"Lavelle","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.1016\/j.apsb.2022.07.002","article-title":"Mucosal vaccine delivery: A focus on the breakthrough of specific barriers","volume":"12","author":"Huang","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Corthesy, B. (2013). Multi-Faceted Functions of Secretory IgA at Mucosal Surfaces. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00185"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Nasiri, O., Hajihassani, M., Goodarzi, N.N., Fereshteh, S., Bolourchi, N., Firoozeh, F., Azizi, O., and Badmasti, F. (2022). Reverse vaccinology approach to identify novel and immunogenic targets against Porphyromonas gingivalis: An in silico study. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0273770"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/s41541-023-00684-0","article-title":"Analyzing immune responses to varied mRNA and protein vaccine sequences","volume":"8","author":"Park","year":"2023","journal-title":"Npj Vaccines"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.intimp.2015.01.007","article-title":"Subcutaneous vaccination with Porphyromonas gingivalis ameliorates periodontitis by modulating Th17\/Treg imbalance in a murine model","volume":"25","author":"Wang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_116","unstructured":"Verschoren, J. (2024). Self-Amplifying RNA Vaccine Design against Canine Periodontitis: Evaluation of Vaccine Antigen Expression by Cell Cultures. [Ph.D. Thesis, Ghent University]."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Huang, T., Peng, L., Han, Y., Wang, D., He, X., Wang, J., and Ou, C. (2022). Lipid nanoparticle-based mRNA vaccines in cancers: Current advances and future prospects. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.922301"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Liu, Y., Huang, Y., He, G., Guo, C., Dong, J., and Wu, L. (2024). Development of mRNA Lipid Nanoparticles: Targeting and Therapeutic Aspects. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251810166"}],"container-title":["Dentistry Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-6767\/13\/2\/79\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:32:58Z","timestamp":1760027578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-6767\/13\/2\/79"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,13]]},"references-count":118,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["dj13020079"],"URL":"https:\/\/doi.org\/10.3390\/dj13020079","relation":{},"ISSN":["2304-6767"],"issn-type":[{"value":"2304-6767","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,13]]}}}