{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:54:16Z","timestamp":1787028856351,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Background\/Objectives: The growing demand for biocompatible and fluoride-free alternatives in oral care has led to the development of formulations containing nano-hydroxyapatite (nanoHAP). This study aimed to evaluate the antimicrobial, antibiofilm, antioxidant, and anti-inflammatory properties of a novel mouthwash containing nanoHAP, zinc lactate, D-panthenol, licorice extract, and cetylpyridinium chloride, with particular focus on its efficacy against Staphylococcus aureus and its biofilm on various dental materials. Methods: The antimicrobial activities of the mouthwash KWT0000 and control product ELM were assessed via minimal inhibitory concentration (MIC) testing against selected Gram-positive and Gram-negative bacteria and Candida fungi. Antibiofilm activity was evaluated using fluorescence and digital microscopy following 1-h exposure to biofilms of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The efficacy was compared across multiple dental materials, including titanium, zirconia, and PMMA. Antioxidant capacity was determined using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay, and anti-inflammatory potential via hyaluronidase inhibition. Results: KWT0000 exhibited strong antimicrobial activity against S. aureus and C. albicans (MICs: 0.2\u20131.6%) and moderate activity against Gram-negative strains. Fluorescence imaging revealed significant biofilm disruption and bacterial death after 1 h. On metallic surfaces, especially polished titanium and zirconia, KWT0000 reduced S. aureus biofilm density considerably. The formulation also demonstrated superior antioxidant (55.33 \u00b1 3.34%) and anti-inflammatory (23.33 \u00b1 3.67%) activity compared to a fluoride-based comparator. Conclusions: The tested nanoHAP-based mouthwash shows promising potential in antimicrobial and antibiofilm oral care, particularly for patients with dental implants. Its multifunctional effects may support not only plaque control but also soft tissue health.<\/jats:p>","DOI":"10.3390\/ma18153567","type":"journal-article","created":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:55:37Z","timestamp":1753872937000},"page":"3567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nano-Hydroxyapatite-Based Mouthwash for Comprehensive Oral Care: Activity Against Bacterial and Fungal Pathogens with Antioxidant and Anti-Inflammatory Action"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6599-9204","authenticated-orcid":false,"given":"Tomasz M.","family":"Karpi\u0144ski","sequence":"first","affiliation":[{"name":"Chair and Department of Medical Microbiology, Poznan University of Medical Sciences, Rokietnicka 10, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0418-9336","authenticated-orcid":false,"given":"Magdalena","family":"Paczkowska-Walendowska","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Science-Bridge Sp. z o.o., Chociszewskiego 24\/8, 60-258 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-5419","authenticated-orcid":false,"given":"Judyta","family":"Cielecka-Piontek","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Science-Bridge Sp. z o.o., Chociszewskiego 24\/8, 60-258 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Singer, L., Fouda, A., and Bourauel, C. (2023). Biomimetic Approaches and Materials in Restorative and Regenerative Dentistry: Review Article. BMC Oral Health, 23.","DOI":"10.1186\/s12903-023-02808-3"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s10266-021-00675-4","article-title":"The Use of Hydroxyapatite Toothpaste to Prevent Dental Caries","volume":"110","author":"Enax","year":"2022","journal-title":"Odontology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lelli, M., Putignano, A., Marchetti, M., Foltran, I., Mangani, F., Procaccini, M., Roveri, N., and Orsini, G. (2014). Remineralization and Repair of Enamel Surface by Biomimetic Zn-Carbonate Hydroxyapatite Containing Toothpaste: A Comparative in Vivo Study. Front. Physiol., 5.","DOI":"10.3389\/fphys.2014.00333"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Boss\u00f9, M., Saccucci, M., Salucci, A., Di Giorgio, G., Bruni, E., Uccelletti, D., Sarto, M.S., Familiari, G., Relucenti, M., and Polimeni, A. (2019). Enamel Remineralization and Repair Results of Biomimetic Hydroxyapatite Toothpaste on Deciduous Teeth: An Effective Option to Fluoride Toothpaste. J. Nanobiotechnol., 17.","DOI":"10.1186\/s12951-019-0454-6"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mao, X., Auer, D.L., Buchalla, W., Hiller, K.-A., Maisch, T., Hellwig, E., Al-Ahmad, A., and Cieplik, F. (2020). Cetylpyridinium Chloride: Mechanism of Action, Antimicrobial Efficacy in Biofilms, and Potential Risks of Resistance. Antimicrob. Agents Chemother., 64.","DOI":"10.1128\/AAC.00576-20"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1021\/acsabm.2c01080","article-title":"One-Pot Preparation of Cetylpyridinium Chloride-Containing Nanoparticles for Biofilm Eradication","volume":"6","author":"Brezhnev","year":"2023","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Seriwatanachai, D., Triratana, T., Kraivaphan, P., Huber, N., Poth, T., Mateo, L.R., Stellitano, M., and Zhang, Y.-P. (2025). Effectiveness of a Novel Amine + Zinc + Fluoride Toothpaste in Reducing Plaque and Gingivitis: Results of a Six-Month Randomized Controlled Trial. BMC Oral Health, 25.","DOI":"10.1186\/s12903-025-05551-z"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/cre2.437","article-title":"An Activated-Zinc Oral Rinse Reduces pro-Inflammatory Cytokine Secretion and Promotes Proliferation in Porphyromonas Gingivalis LPS-Challenged Gingival Tissues\u2014A Pilot Study","volume":"7","author":"Stanton","year":"2021","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s00784-023-05487-0","article-title":"Antibacterial and Clinical Effectiveness of a Mouthwash with a Novel Active System of Amine + Zinc Lactate + Fluoride: A Randomized Controlled Trial","volume":"28","author":"Montesani","year":"2024","journal-title":"Clin. Oral. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.5005\/jp-journals-10024-2421","article-title":"Clinical Impact and Cosmetic Acceptability of Chlorhexidineenriched Toothpaste and Mouthwash Application on Periodontal Disease: A Randomized Clinical Study","volume":"19","author":"Magaz","year":"2018","journal-title":"J. Contemp. Dent. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"427","DOI":"10.2165\/00128071-200203060-00005","article-title":"Topical Use of Dexpanthenol in Skin Disorders","volume":"3","author":"Ebner","year":"2002","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1186\/s12967-022-03636-9","article-title":"Host-Microbiome Interactions Regarding Peri-Implantitis and Dental Implant Loss","volume":"20","author":"Alves","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_13","first-page":"CD003809","article-title":"Fluorides for Preventing Early Tooth Decay (Demineralised Lesions) during Fixed Brace Treatment","volume":"2019","author":"Benson","year":"2019","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Paszynska, E., Pawinska, M., Gawriolek, M., Kaminska, I., Otulakowska-Skrzynska, J., Marczuk-Kolada, G., Rzatowski, S., Sokolowska, K., Olszewska, A., and Schlagenhauf, U. (2021). Impact of a Toothpaste with Microcrystalline Hydroxyapatite on the Occurrence of Early Childhood Caries: A 1-Year Randomized Clinical Trial. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-81112-y"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e12399","DOI":"10.1111\/jicd.12399","article-title":"Impact of a Non-Fluoridated Microcrystalline Hydroxyapatite Dentifrice on Enamel Caries Progression in Highly Caries-Susceptible Orthodontic Patients: A Randomized, Controlled 6-Month Trial","volume":"10","author":"Schlagenhauf","year":"2019","journal-title":"J. Investig. Clin. Dent."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Paszynska, E., Pawinska, M., Enax, J., Meyer, F., Schulze zur Wiesche, E., May, T.W., Amaechi, B.T., Limeback, H., Hernik, A., and Otulakowska-Skrzynska, J. (2023). Caries-Preventing Effect of a Hydroxyapatite-Toothpaste in Adults: A 18-Month Double-Blinded Randomized Clinical Trial. Front. Public Health, 11.","DOI":"10.3389\/fpubh.2023.1199728"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cieplik, F., Rupp, C.M., Hirsch, S., Muehler, D., Enax, J., Meyer, F., Hiller, K.-A., and Buchalla, W. (2020). Ca2+ Release and Buffering Effects of Synthetic Hydroxyapatite Following Bacterial Acid Challenge. BMC Oral Health, 20.","DOI":"10.1186\/s12903-020-01080-z"},{"key":"ref_18","first-page":"28","article-title":"Anti-Candida and Antibiofilm Activity of Selected Lamiaceae Essential Oils","volume":"28","author":"Wolski","year":"2023","journal-title":"FBL"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Karpi\u0144ski, T.M., O\u017carowski, M., Paczkowska-Walendowska, M., and Cielecka-Piontek, J. (2025). Astaxanthin Demonstrates Moderate or Weak Activity against Bacterial and Fungal Pathogens. Food Biosci., 65.","DOI":"10.1016\/j.fbio.2025.106026"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Paczkowska-Walendowska, M., Go\u015bciniak, A., Szymanowska, D., Szwajgier, D., Baranowska-W\u00f3jcik, E., Szulc, P., Dreczka, D., Simon, M., and Cielecka-Piontek, J. (2021). Blackberry Leaves as New Functional Food? Screening Antioxidant, Anti-Inflammatory and Microbiological Activities in Correlation with Phytochemical Analysis. Antioxidants, 10.","DOI":"10.3390\/antiox10121945"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3390\/nu2030290","article-title":"Streptococcus Mutans, Caries and Simulation Models","volume":"2","author":"Forssten","year":"2010","journal-title":"Nutrients"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ajic.2014.09.015","article-title":"Staphylococcus aureus and the Oral Cavity: An Overlooked Source of Carriage and Infection?","volume":"43","author":"McCormack","year":"2015","journal-title":"Am. J. Infect. Control"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1007\/s00203-021-02300-y","article-title":"Presence of Non-Oral Bacteria in the Oral Cavity","volume":"203","author":"Zaatout","year":"2021","journal-title":"Arch. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2272","DOI":"10.1016\/j.identj.2024.11.020","article-title":"Advances of Hydroxyapatite Nanoparticles in Dental Implant Applications","volume":"75","author":"Islam","year":"2025","journal-title":"Int. Dent. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.sdentj.2023.05.018","article-title":"Nanohydroxyapatite in Dentistry: A Comprehensive Review","volume":"35","author":"Pushpalatha","year":"2023","journal-title":"Saudi Dent. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s11671-025-04206-w","article-title":"Advances in Macro-Bioactive Materials Enhancing Dentin Bonding","volume":"20","author":"Fan","year":"2025","journal-title":"Discov. Nano"},{"key":"ref_27","first-page":"478","article-title":"Electrospun Nanofibrous Membranes Meet Antibacterial Nanomaterials: From Preparation Strategies to Biomedical Applications","volume":"42","author":"Chen","year":"2024","journal-title":"Bioact. Mater."},{"key":"ref_28","first-page":"44","article-title":"Simvastatin-Hydroxyapatite Coatings Prevent Biofilm Formation and Improve Bone Formation in Implant-Associated Infections","volume":"21","author":"Sun","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Abdelghafar, A., Yousef, N., and Askoura, M. (2022). Zinc Oxide Nanoparticles Reduce Biofilm Formation, Synergize Antibiotics Action and Attenuate Staphylococcus aureus Virulence in Host; an Important Message to Clinicians. BMC Microbiol., 22.","DOI":"10.1186\/s12866-022-02658-z"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/13880209.2016.1225775","article-title":"The Anti-Inflammatory Activity of Licorice, a Widely Used Chinese Herb","volume":"55","author":"Yang","year":"2016","journal-title":"Pharm. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9988167","DOI":"10.1155\/2024\/9988167","article-title":"Exploring the Role of Licorice and Its Derivatives in Cell Signaling Pathway NF-\u03baB and MAPK","volume":"2024","author":"Fatima","year":"2024","journal-title":"J. Nutr. Metab."},{"key":"ref_32","first-page":"88","article-title":"Evaluating the Effects of a Topical Preparation with Dexpanthenol, Silbiol, Undecylenic Acid, and Lidocaine on Palatal Mucosa Wound Healing in a Rat Model","volume":"36","author":"Sezgin","year":"2019","journal-title":"Balk. Med. J."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Marreiro, D.D.N., Cruz, K.J.C., Morais, J.B.S., Beserra, J.B., Severo, J.S., and de Oliveira, A.R.S. (2017). Zinc and Oxidative Stress: Current Mechanisms. Antioxidants, 6.","DOI":"10.3390\/antiox6020024"},{"key":"ref_34","first-page":"108","article-title":"Nano-Hydroxyapatite and Its Applications in Preventive, Restorative and Regenerative Dentistry: A Review of Literature","volume":"5","author":"Pepla","year":"2014","journal-title":"Ann. Stomatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.identj.2022.01.005","article-title":"Chlorhexidine in Dentistry: Pharmacology, Uses, and Adverse Effects","volume":"72","author":"Ouanounou","year":"2022","journal-title":"Int. Dent. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1128\/CMR.12.1.147","article-title":"Antiseptics and Disinfectants: Activity, Action, and Resistance","volume":"12","author":"McDonnell","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_37","first-page":"CD008676","article-title":"Chlorhexidine Mouthrinse as an Adjunctive Treatment for Gingival Health","volume":"2017","author":"James","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/idh.12392","article-title":"Effect of Toothpaste Containing Amine Fluoride and Stannous Chloride on the Reduction of Dental Plaque and Gingival Inflammation. A Randomized Controlled 12-Week Home-Use Study","volume":"17","author":"Lorenz","year":"2019","journal-title":"Int. J. Dent. Hyg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1002\/JPER.22-0675","article-title":"A Randomized Double-Blind Clinical Trial Evaluating Comparative Plaque and Gingival Health Associated with Commercially Available Stannous Fluoride-Containing Dentifrices as Compared to a Sodium Fluoride Control Dentifrice","volume":"94","author":"Geisinger","year":"2023","journal-title":"J. Periodontol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Pompilio, A., Scribano, D., Sarshar, M., Di Bonaventura, G., Palamara, A.T., and Ambrosi, C. (2021). Gram-Negative Bacteria Holding Together in a Biofilm: The Acinetobacter Baumannii Way. Microorganisms, 9.","DOI":"10.3390\/microorganisms9071353"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1034\/j.1600-051X.30.s5.4.x","article-title":"Penetrating the Plaque Biofilm: Impact of Essential Oil Mouthwash","volume":"30","author":"Ouhayoun","year":"2003","journal-title":"J. Clin. Periodontol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Maziere, M., Rompante, P., Andrade, J.C., and Rodrigues, C.F. (2024). Are Mouthwashes Really Effective against Candida spp.?. J. Fungi, 10.","DOI":"10.3390\/jof10080528"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Luo, S.-C., Wei, S.-M., Luo, X.-T., Yang, Q.-Q., Wong, K.-H., Cheung, P.C.K., and Zhang, B.-B. (2024). How Probiotics, Prebiotics, Synbiotics, and Postbiotics Prevent Dental Caries: An Oral Microbiota Perspective. npj Biofilms Microbiomes, 10.","DOI":"10.1038\/s41522-024-00488-7"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Paczkowska-Walendowska, M., Grzegorzewski, J., Kwiatek, J., Le\u015bna, M., and Cielecka-Piontek, J. (2025). Green Tea: A Novel Perspective on the Traditional Plant\u2019s Potential in Managing Periodontal Diseases. Pharmaceuticals, 18.","DOI":"10.3390\/ph18030409"}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/18\/15\/3567\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:18:44Z","timestamp":1760033924000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/18\/15\/3567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,30]]},"references-count":44,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ma18153567"],"URL":"https:\/\/doi.org\/10.3390\/ma18153567","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,30]]}}}