Emerging roles of plant-derived extracellular vesicles in the management of dental diseases

Abstract

Dental diseases, including dental caries, pulpitis, and periodontitis, can cause pain and tooth loss, compromising mastication, speech, aesthetics, and quality of life. These diseases have also been associated with systemic disorders, including Alzheimer’s disease. Conventional interventions, such as restorative procedures, root canal treatment, and periodontal scaling, have inherent limitations, underscoring the clinical need for novel therapeutic strategies. Plant-derived extracellular vesicles (PDEVs) have recently attracted considerable attention owing to their wide availability, cost-effectiveness, favourable biosafety profile, and capacity to mediate cross-kingdom communication. PDEVs exert diverse biological effects, including antimicrobial, anti-inflammatory, immunomodulatory, and tissue-regenerative activities. For example, ginger-derived PDEVs suppress the growth and virulence of Porphyromonas gingivalis through their lipid and miRNA cargoes, thereby alleviating periodontitis in mice. Given that effective dental therapy requires antimicrobial action, anti-inflammatory effects, immunomodulation, and tissue regeneration, PDEVs are promising therapeutic modalities. This review summarises the isolation, characterisation, composition, and biological functions of PDEVs, and discusses their potential applications in the management of dental diseases.

Keywords

Plant-derived extracellular vesicles / dental diseases / microorganisms / inflammation / tissue regeneration

References

[1] World Health Organization. Global oral health status report: towards universal health coverage for oral health by 2030. Available from https://www.who.int/publications/i/item/9789240061484. [accessed 18 September 2026]

[2] Bui FQ,Almeida-da-Silva CLC,Huynh B.et al. Association between periodontal pathogens and systemic disease Biomed J 2019 42 27 35 PMC6468093

[3] Hajishengallis G,Chavakis T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities Nat Rev Immunol 2021 21 426 40 PMC7841384

[4] World Health Organization Regional Office for South-East Asia. Pharmacovigilance for traditional medicine products: why and how? Available from https://www.who.int/publications/i/item/10665-259854. [accessed 18 September 2026]

[5] Feng J,Xiu Q,Huang Y,Troyer Z,Li B,Zheng L. Plant-derived vesicle-like nanoparticles as promising biotherapeutic tools: present and future Adv Mater 2023 35 e2207826

[6] Song H,Canup BSB,Ngo VL,Denning TL,Garg P,Laroui H. Internalization of garlic-derived nanovesicles on liver cells is triggered by interaction with CD98 ACS Omega 2020 5 23118 28 PMC7495725

[7] Welsh JA,Goberdhan DCI,O’Driscoll L.et al. ; MISEV Consortium. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches J Extracell Vesicles 2024 13 e12404 PMC10850029

[8] Pinedo M,de la Canal L,de Marcos Lousa C. A call for Rigor and standardization in plant extracellular vesicle research J Extracell Vesicles 2021 10 e12048 PMC8077130

[9] Halperin W,Jensen WA. Ultrastructural changes during growth and embryogenesis in carrot cell cultures J Ultrastruct Res 1967 18 428 43

[10] Regente M,Corti-Monzón G,Maldonado AM,Pinedo M,Jorrín J,de la Canal L. Vesicular fractions of sunflower apoplastic fluids are associated with potential exosome marker proteins FEBS Lett 2009 583 3363 6

[11] He B,Cai Q,Qiao L.et al. RNA-binding proteins contribute to small RNA loading in plant extracellular vesicles Nat Plants 2021 7 342 52 PMC7979528

[12] Gao J,Li Y,Zhang S.et al. Structural and functional characterization of EXPO-derived extracellular vesicles in plants Adv Sci 2026 13 e06163 PMC12970281

[13] Koch BL,Rutter BD,Borniego ML,Singla-Rastogi M,Gardner DM,Innes RW. Arabidopsis produces distinct subpopulations of extracellular vesicles that respond differentially to biotic stress, altering growth and infectivity of a fungal pathogen J Extracell Vesicles 2025 14 e70090 PMC12104214

[14] Caponnetto F,Manini I,Skrap M.et al. Size-dependent cellular uptake of exosomes Nanomedicine 2017 13 1011 20

[15] Xu M,Qi Y,Liu G,Song Y,Jiang X,Du B. Size-dependent in vivo transport of nanoparticles: implications for delivery, targeting, and clearance ACS Nano 2023 17 20825 49

[16] Lian MQ,Chng WH,Liang J.et al. Plant-derived extracellular vesicles: recent advancements and current challenges on their use for biomedical applications J Extracell Vesicles 2022 11 e12283 PMC9753580

[17] Kocholata M,Maly J,Martinec J,Auer Malinska H. Plant extracellular vesicles and their potential in human health research, the practical approach Physiol Res 2022 71 327 39 PMC9470093

[18] Liu Y,Wu S,Koo Y.et al. Characterization of and isolation methods for plant leaf nanovesicles and small extracellular vesicles Nanomedicine 2020 29 102271

[19] Sundaram K,Mu J,Kumar A.et al. Garlic exosome-like nanoparticles reverse high-fat diet induced obesity via the gut/brain axis Theranostics 2022 12 1220 46 PMC8771565

[20] Zhao Q,Liu G,Liu F.et al. An enzyme-based system for extraction of small extracellular vesicles from plants Sci Rep 2023 13 13931 PMC10457285

[21] Wang Q,Jing R,Cao N.et al. Generalizability of enzyme-based isolation approach for extracellular vesicles from traditional medicinal plants J Extracell Biol 2025 4 e70090 PMC12479721

[22] Rutter BD,Innes RW. Extracellular vesicles isolated from the leaf apoplast carry stress-response proteins Plant Physiol 2017 173 728 41 PMC5210723

[23] Zhuang X,Teng Y,Samykutty A.et al. Grapefruit-derived nanovectors delivering therapeutic miR17 through an intranasal route inhibit brain tumor progression Mol Ther 2016 24 96 105 PMC4754550

[24] Konoshenko MY,Lekchnov EA,Vlassov AV,Laktionov PP. Isolation of extracellular vesicles: general methodologies and latest trends Biomed Res Int 2018 2018 8545347 PMC5831698

[25] Li P,Kaslan M,Lee SH,Yao J,Gao Z. Progress in exosome isolation techniques Theranostics 2017 7 789 804 PMC5327650

[26] Akbar A,Malekian F,Baghban N,Kodam SP,Ullah M. Methodologies to isolate and purify clinical grade extracellular vesicles for medical applications Cells 2022 11 186 PMC8774122

[27] Kalarikkal SP,Prasad D,Kasiappan R,Chaudhari SR,Sundaram GM. A cost-effective polyethylene glycol-based method for the isolation of functional edible nanoparticles from ginger rhizomes Sci Rep 2020 10 4456 PMC7064537

[28] Suresh AP,Kalarikkal SP,Pullareddy B,Sundaram GM. Low pH-based method to increase the yield of plant-derived nanoparticles from fresh ginger rhizomes ACS Omega 2021 6 17635 41 PMC8280662

[29] Mao X,Li T,Qi W.et al. Advances in the study of plant-derived extracellular vesicles in the skeletal muscle system Pharmacol Res 2024 204 107202

[30] Liangsupree T,Multia E,Riekkola ML. Modern isolation and separation techniques for extracellular vesicles J Chromatogr A 2021 1636 461773

[31] Ansari FJ,Tafti HA,Amanzadeh A.et al. Comparison of the efficiency of ultrafiltration, precipitation, and ultracentrifugation methods for exosome isolation Biochem Biophys Rep 2024 38 101668 PMC10885727

[32] Wu P,Wu W,Zhang S.et al. Therapeutic potential and pharmacological significance of extracellular vesicles derived from traditional medicinal plants Front Pharmacol 2023 14 1272241 PMC10725203

[33] Sidhom K,Obi PO,Saleem A. A review of exosomal isolation methods: is size exclusion chromatography the best option? Int J Mol Sci 2020;21:6466 PMC7556044

[34] Bokka R,Ramos AP,Fiume I.et al. Biomanufacturing of tomato-derived nanovesicles Foods 2020 9 1852 PMC7764365

[35] Sánchez-López CM,Manzaneque-López MC,Pérez-Bermúdez P,Soler C,Marcilla A. Characterization and bioactivity of extracellular vesicles isolated from pomegranate Food Funct 2022 13 12870 82

[36] Yang M,Liu X,Luo Q,Xu L,Chen F. An efficient method to isolate lemon derived extracellular vesicles for gastric cancer therapy J Nanobiotechnology 2020 18 100 PMC7370524

[37] Jackson KK,Mata C,Marcus RK. A rapid capillary-channeled polymer (C-CP) fiber spin-down tip approach for the isolation of plant-derived extracellular vesicles (PDEVs) from 20 common fruit and vegetable sources Talanta 2023 252 123779

[38] Ming T,Yang Y,Zhu J.et al. Ginger-derived exosome-like nanoparticles: the effect of extraction methods on metabolites and in vitro anti-lung cancer activity Int J Nanomedicine 2025 20 13399 420 PMC12599200

[39] Kocholata M,Prusova M,Auer Malinska H,Maly J,Janouskova O. Comparison of two isolation methods of tobacco-derived extracellular vesicles, their characterization and uptake by plant and rat cells Sci Rep 2022 12 19896 PMC9674704

[40] Mammadova R,Fiume I,Bokka R.et al. Identification of tomato infecting viruses that co-isolate with nanovesicles using a combined proteomics and electron-microscopic approach Nanomaterials 2021 11 1922 PMC8399691

[41] Li A,Li D,Gu Y.et al. Plant-derived nanovesicles: further exploration of biomedical function and application potential Acta Pharm Sin B 2023 13 3300 20 PMC10465964

[42] Logozzi M,Di Raimo R,Mizzoni D,Fais S. Nanovesicles from organic agriculture-derived fruits and vegetables: characterization and functional antioxidant content Int J Mol Sci 2021 22 8170 PMC8347793

[43] Midekessa G,Godakumara K,Ord J.et al. Zeta potential of extracellular vesicles: toward understanding the attributes that determine colloidal stability ACS Omega 2020 5 16701 10 PMC7364712

[44] Tamrin SH,Phelps J,Nezhad AS,Sen A. Critical considerations in determining the surface charge of small extracellular vesicles J Extracell Vesicles 2023 12 e12353 PMC10457570

[45] de la Canal L,Pinedo M. Extracellular vesicles: a missing component in plant cell wall remodeling J Exp Bot 2018 69 4655 8 PMC6137967

[46] Ekanayake G,Piibor J,Midekessa G.et al. Systematic characterization of extracellular vesicles from potato (Solanum tuberosum cv. Laura) roots and peels: biophysical properties and proteomic profiling Front Plant Sci 2024 15 1477614 PMC11607679

[47] Cai Q,Qiao L,Wang M.et al. Plants send small RNAs in extracellular vesicles to fungal pathogen to silence virulence genes Science 2018 360 1126 9 PMC6442475

[48] Karamanidou T,Tsouknidas A. Plant-derived extracellular vesicles as therapeutic nanocarriers Int J Mol Sci 2021 23 191 PMC8745116

[49] Zeng L,Wang H,Shi W.et al. Aloe derived nanovesicle as a functional carrier for indocyanine green encapsulation and phototherapy J Nanobiotechnology 2021 19 439 PMC8686546

[50] Liu NJ,Wang N,Bao JJ,Zhu HX,Wang LJ,Chen XY. Lipidomic analysis reveals the importance of GIPCs in Arabidopsis leaf extracellular vesicles Mol Plant 2020 13 1523 32

[51] Egea-Jimenez AL,Zimmermann P. Phospholipase D and phosphatidic acid in the biogenesis and cargo loading of extracellular vesicles J Lipid Res 2018 59 1554 60 PMC6121939

[52] Teng Y,Ren Y,Sayed M.et al. Plant-derived exosomal microRNAs shape the gut microbiota Cell Host Microbe 2018 24 637 52.e8 PMC6746408

[53] Yi Q,Xu Z,Thakur A.et al. Current understanding of plant-derived exosome-like nanoparticles in regulating the inflammatory response and immune system microenvironment Pharmacol Res 2023 190 106733

[54] Eros G,Varga G,Váradi R.et al. Anti-inflammatory action of a phosphatidylcholine, phosphatidylethanolamine and N-acylphosphatidylethanolamine-enriched diet in carrageenan-induced pleurisy Eur Surg Res 2009 42 40 8

[55] Wang B,Zhuang X,Deng ZB.et al. Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit Mol Ther 2014 22 522 34 PMC3944329

[56] Cao M,Yan H,Han X.et al. Ginseng-derived nanoparticles alter macrophage polarization to inhibit melanoma growth J Immunother Cancer 2019 7 326 PMC6882204

[57] Martínez-Ballesta MDC,García-Gomez P,Yepes-Molina L,Guarnizo AL,Teruel JA,Carvajal M. Plasma membrane aquaporins mediates vesicle stability in broccoli PLoS One 2018 13 e0192422 PMC5805300

[58] De Palma M,Ambrosone A,Leone A.et al. Plant roots release small extracellular vesicles with antifungal activity Plants 2020 9 1777 PMC7765200

[59] Liu G,Kang G,Wang S,Huang Y,Cai Q. Extracellular vesicles: emerging players in plant defense against pathogens Front Plant Sci 2021 12 757925 PMC8515046

[60] Yang M,Luo Q,Chen X,Chen F. Bitter melon derived extracellular vesicles enhance the therapeutic effects and reduce the drug resistance of 5-fluorouracil on oral squamous cell carcinoma J Nanobiotechnology 2021 19 259 PMC8400897

[61] Sriwastva MK,Deng ZB,Wang B.et al. Exosome-like nanoparticles from Mulberry bark prevent DSS-induced colitis via the AhR/COPS8 pathway EMBO Rep 2022 23 e53365 PMC8892346

[62] Chin AR,Fong MY,Somlo G.et al. Cross-kingdom inhibition of breast cancer growth by plant miR159 Cell Res 2016 26 217 28 PMC4746606

[63] Xiao J,Feng S,Wang X.et al. Identification of exosome-like nanoparticle-derived microRNAs from 11 edible fruits and vegetables PeerJ 2018 6 e5186 PMC6074755

[64] Qiu FS,Wang JF,Guo MY.et al. Rgl-exomiR-7972, a novel plant exosomal microRNA derived from fresh Rehmanniae Radix, ameliorated lipopolysaccharide-induced acute lung injury and gut dysbiosis Biomed Pharmacother 2023 165 115007

[65] Sundaram K,Miller DP,Kumar A.et al. Plant-derived exosomal nanoparticles inhibit pathogenicity of Porphyromonas gingivalis iScience 2020 23 100869 PMC7054809

[66] Zhu H,Chang M,Wang Q,Chen J,Liu D,He W. Identifying the potential of miRNAs in Houttuynia cordata-derived exosome-like nanoparticles against respiratory RNA viruses Int J Nanomedicine 2023 18 5983 6000 PMC10612503

[67] Marzocchella L,Fantini M,Benvenuto M.et al. Dietary flavonoids: molecular mechanisms of action as anti- inflammatory agents Recent Pat Inflamm Allergy Drug Discov 2011 5 200 20

[68] Mena P,Angelino D. Plant food, nutrition, and human health Nutrients 2020 12 2157 PMC7400879

[69] Zhang M,Viennois E,Prasad M.et al. Edible ginger-derived nanoparticles: a novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer Biomaterials 2016 101 321 40 PMC4921206

[70] Zhuang X,Deng ZB,Mu J.et al. Ginger-derived nanoparticles protect against alcohol-induced liver damage J Extracell Vesicles 2015 4 28713 PMC4662062

[71] Man F,Meng C,Liu Y.et al. The study of ginger-derived extracellular vesicles as a natural nanoscale drug carrier and their intestinal absorption in rats AAPS PharmSciTech 2021 22 206

[72] Zeng W,Jin L,Zhang F,Zhang C,Liang W. Naringenin as a potential immunomodulator in therapeutics Pharmacol Res 2018 135 122 6

[73] Deng Z,Rong Y,Teng Y.et al. Broccoli-derived nanoparticle inhibits mouse colitis by activating dendritic cell AMP-activated protein kinase Mol Ther 2017 25 1641 54 PMC5498816

[74] Lai H,Li J,Kou X,Mao X,Zhao W,Ma L. Extracellular vesicles for dental pulp and periodontal regeneration Pharmaceutics 2023 15 282 PMC9862817

[75] Li Y,Duan X,Chen Y,Liu B,Chen G. Dental stem cell-derived extracellular vesicles as promising therapeutic agents in the treatment of diseases Int J Oral Sci 2022 14 2 PMC8724288

[76] Sall IM,Flaviu TA. Plant and mammalian-derived extracellular vesicles: a new therapeutic approach for the future Front Bioeng Biotechnol 2023 11 1215650 PMC10534050

[77] Spatafora G,Li Y,He X,Cowan A,Tanner ACR. The evolving microbiome of dental caries Microorganisms 2024 12 121 PMC10819217

[78] Fouad AF,Khan AA. Etiology and pathogenesis of pulpitis and apical periodontitis. In: Ørstavik D, Editor. Essential endodontology. Wiley; 2019. pp. 59-90

[79] Davis JM,Maki J,Bahcall JK. An in vitro comparison of the antimicrobial effects of various endodontic medicaments on Enterococcus faecalis J Endod 2007 33 567 9

[80] Łasica A,Golec P,Laskus A,Zalewska M,Gędaj M,Popowska M. Periodontitis: etiology, conventional treatments, and emerging bacteriophage and predatory bacteria therapies Front Microbiol 2024 15 1469414 PMC11464445

[81] Persson GR,Renvert S. Cluster of bacteria associated with peri-implantitis Clin Implant Dent Relat Res 2014 16 783 93

[82] Zhou S,Huang P,Cao Y,Hua X,Yang Y,Liu S. Garlic-derived exosome-like nanovesicles-based wound dressing for Staphylococcus aureus infection visualization and treatment ACS Appl Bio Mater 2024 7 1888 98

[83] Zhu Z,Liao L,Gao M,Liu Q. Garlic-derived exosome-like nanovesicles alleviate dextran sulphate sodium-induced mouse colitis via the TLR4/MyD88/NF-κB pathway and gut microbiota modulation Food Funct 2023 14 7520 34

[84] Schuh CMAP,Aguayo S,Zavala G,Khoury M. Exosome-like vesicles in Apis mellifera bee pollen, honey and royal jelly contribute to their antibacterial and pro-regenerative activity J Exp Biol 2019 222 jeb208702

[85] Gao C,Zhou Y,Chen Z.et al. Turmeric-derived nanovesicles as novel nanobiologics for targeted therapy of ulcerative colitis Theranostics 2022 12 5596 614 PMC9330521

[86] Lei C,Teng Y,He L.et al. Lemon exosome-like nanoparticles enhance stress survival of gut bacteria by RNase P-mediated specific tRNA decay iScience 2021 24 102511 PMC8188359

[87] Lee BH,Wu SC,Chien HY,Shen TL,Hsu WH. Tomato-fruit-derived extracellular vesicles inhibit Fusobacterium nucleatum via lipid-mediated mechanism Food Funct 2023 14 8942 50

[88] Tan S,Liu Z,Cong M.et al. Dandelion-derived vesicles-laden hydrogel dressings capable of neutralizing Staphylococcus aureus exotoxins for the care of invasive wounds J Control Release 2024 368 355 71

[89] Liu Y,Tan ML,Zhu WJ.et al. In vitro effects of tartary buckwheat-derived nanovesicles on gut microbiota J Agric Food Chem 2022 70 2616 29

[90] Li D,Yi G,Cao G.et al. Dual-carriers of tartary buckwheat-derived exosome-like nanovesicles synergistically regulate glucose metabolism in the intestine-liver axis Small 2025 21 e2410124

[91] Zhan W,Deng M,Huang X.et al. Pueraria lobata-derived exosome-like nanovesicles alleviate osteoporosis by enhacning autophagy J Control Release 2023 364 644 53

[92] Zhu MZ,Xu HM,Liang YJ.et al. Edible exosome-like nanoparticles from Portulaca oleracea L mitigate DSS-induced colitis via facilitating double-positive CD4⁺CD8⁺T cells expansion J Nanobiotechnology 2023 21 309 PMC10469825

[93] Ma Y,Yang K,Hu H.et al. Comparative analysis of the composition of exosome-like nanoparticles from dried and fresh Portulaca oleracea L Molecules 2025 30 4715 PMC12736374

[94] Pohl S,Akamp T,Smeda M.et al. Understanding dental pulp inflammation: from signaling to structure Front Immunol 2024 15 1474466 PMC11554472

[95] Ye L,Cao L,Song W,Yang C,Tang Q,Yuan Z. Interaction between apical periodontitis and systemic disease (Review) Int J Mol Med 2023 52 60 PMC10249585

[96] Kinane DF,Stathopoulou PG,Papapanou PN. Periodontal diseases Nat Rev Dis Primers 2017 3 17038

[97] Assery NM,Jurado CA,Assery MK,Afrashtehfar KI. Peri-implantitis and systemic inflammation: a critical update Saudi Dent J 2023 35 443 50 PMC10373087

[98] Xie Q,Gu J,Sun Y.et al. Therapeutic potential of ginger exosome-like nanoparticles for alleviating periodontitis-induced tissue damage Int J Nanomedicine 2024 19 11941 56 PMC11577593

[99] Yan L,Cao Y,Hou L.et al. Ginger exosome-like nanoparticle-derived miRNA therapeutics: a strategic inhibitor of intestinal inflammation J Adv Res 2025 69 1 15 PMC11954804

[100] Wu J,Ma X,Lu Y.et al. Edible Pueraria lobata-derived exosomes promote M2 macrophage polarization Molecules 2022 27 8184 PMC9735656

[101] Vanessa V,Rachmawati H,Barlian A. Anti-inflammatory potential of goldenberry-derived exosome-like nanoparticles in macrophage polarization Future Sci OA 2024 10 FSO943 PMC11140644

[102] Han R,Zhou D,Ji N.et al. Folic acid-modified ginger-derived extracellular vesicles for targeted treatment of rheumatoid arthritis by remodeling immune microenvironment via the PI3K-AKT pathway J Nanobiotechnology 2025 23 41 PMC11756199

[103] You JY,Kang SJ,Rhee WJ. Isolation of cabbage exosome-like nanovesicles and investigation of their biological activities in human cells Bioact Mater 2021 6 4321 32 PMC8105599

[104] Liu B,Li X,Yu H.et al. Therapeutic potential of garlic chive-derived vesicle-like nanoparticles in NLRP3 inflammasome-mediated inflammatory diseases Theranostics 2021 11 9311 30 PMC8490522

[105] De Robertis M,Sarra A,D’Oria V.et al. Blueberry-derived exosome-like nanoparticles counter the response to TNF-α-induced change on gene expression in EA.hy926 cells Biomolecules 2020 10 742 PMC7277966

[106] Perut F,Roncuzzi L,Avnet S.et al. Strawberry-derived exosome-like nanoparticles prevent oxidative stress in human mesenchymal stromal cells Biomolecules 2021 11 87 PMC7828105

[107] Zu M,Xie D,Canup BSB.et al. ‘Green’ nanotherapeutics from tea leaves for orally targeted prevention and alleviation of colon diseases Biomaterials 2021 279 121178

[108] Aquilano K,Ceci V,Gismondi A.et al. Adipocyte metabolism is improved by TNF receptor-targeting small RNAs identified from dried nuts Commun Biol 2019 2 317 PMC6704100

[109] Kim M,Park JH. Isolation of Aloe saponaria-derived extracellular vesicles and investigation of their potential for chronic wound healing Pharmaceutics 2022 14 1905 PMC9504946

[110] Valentino A,Conte R,Bousta D.et al. Extracellular vesicles derived from Opuntia ficus-indica Fruit (OFI-EVs) speed up the normal wound healing processes by modulating cellular responses Int J Mol Sci 2024 25 7103 PMC11241772

[111] Kim H,Shin HY,Park M,Ahn K,Kim SJ,An SH. Exosome-like vesicles from Lithospermum erythrorhizon callus enhanced wound healing by reducing LPS-induced inflammation J Microbiol Biotechnol 2024 35 e2410022 PMC11813354

[112] Şahin F, Koçak P, Güneş MY, Özkan İ, Yıldırım E, Kala EY. In vitro wound healing activity of wheat-derived nanovesicles Appl Biochem Biotechnol 2019 188 381 94

[113] Cui WW,Ye C,Wang KX.et al. Momordica. charantia-derived extracellular vesicles-like nanovesicles protect cardiomyocytes against radiation injury via attenuating DNA damage and mitochondria dysfunction Front Cardiovasc Med 2022 9 864188 PMC9058095

[114] Ju S,Mu J,Dokland T.et al. Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis Mol Ther 2013 21 1345 57 PMC3702113

[115] Hwang JH,Park YS,Kim HS.et al. Yam-derived exosome-like nanovesicles stimulate osteoblast formation and prevent osteoporosis in mice J Control Release 2023 355 184 98

[116] Sim Y,Seo HJ,Kim DH.et al. The effect of apple-derived nanovesicles on the osteoblastogenesis of osteoblastic MC3T3-E1 cells J Med Food 2023 26 49 58

[117] Park YS,Kim HW,Hwang JH.et al. Plum-derived exosome-like nanovesicles induce differentiation of osteoblasts and reduction of osteoclast activation Nutrients 2023 15 2107 PMC10180726

[118] Zhao Q,Feng J,Liu F.et al. Rhizoma Drynariae-derived nanovesicles reverse osteoporosis by potentiating osteogenic differentiation of human bone marrow mesenchymal stem cells via targeting ERα signaling Acta Pharm Sin B 2024 14 2210 27 PMC11119514

[119] Xu XH,Yuan TJ,Dad HA.et al. Plant exosomes as novel nanoplatforms for microRNA transfer stimulate neural differentiation of stem cells in vitro and in vivo Nano Lett 2021 21 8151 9

[120] Mahdipour E. Beta vulgaris juice contains biologically active exosome-like nanoparticles Tissue Cell 2022 76 101800

[121] Chen F,Wang D. Novel technologies for the prevention and treatment of dental caries: a patent survey Expert Opin Ther Pat 2010 20 681 94 PMC2857592

[122] Schwendicke F,Tu YK,Hsu LY,Göstemeyer G. Antibacterial effects of cavity lining: a systematic review and network meta-analysis J Dent 2015 43 1298 307

[123] Tomson PL,Duncan HF. Pulp capping materials for the maintenance of pulp vitality. In: Camilleri J, Editor. Endodontic materials in clinical practice. Wiley; 2021. pp. 15-45

[124] Leiva-Sabadini C,Alvarez S,Barrera NP,Schuh CMAP,Aguayo S. Antibacterial effect of honey-derived exosomes containing antimicrobial peptides against oral streptococci Int J Nanomedicine 2021 16 4891 900 PMC8312616

[125] Bowen WH,Koo H. Biology of Streptococcus mutans-derived glucosyltransferases: role in extracellular matrix formation of cariogenic biofilms Caries Res 2011 45 69 86 PMC3068567

[126] Tran XV,Gorin C,Willig C.et al. Effect of a calcium-silicate-based restorative cement on pulp repair J Dent Res 2012 91 1166 71

[127] Stuart CH,Schwartz SA,Beeson TJ,Owatz CB. Enterococcus faecalis: its role in root canal treatment failure and current concepts in retreatment J Endod 2006 32 93 8

[128] Pascon FM,Kantovitz KR,Sacramento PA,Nobre-dos-Santos M,Puppin-Rontani RM. Effect of sodium hypochlorite on dentine mechanical properties. A review J Dent 2009 37 903 8

[129] Zehnder M. Root canal irrigants J Endod 2006 32 389 98

[130] Komabayashi T,Colmenar D,Cvach N,Bhat A,Primus C,Imai Y. Comprehensive review of current endodontic sealers Dent Mater J 2020 39 703 20

[131] Gasner NS,Brizuela M. Endodontic materials used to fill root canals. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Available from https://www.ncbi.nlm.nih.gov/books/NBK587367/. [accessed 18 September 2026]

[132] Nesbit SP,Gonzalez-cabezas C,Reside J.et al. Disease control phase of treatment. Diagnosis and treatment planning in dentistry. Elsevier; 2017. pp. 192-225.e1

[133] Graziani F,Karapetsa D,Alonso B,Herrera D. Nonsurgical and surgical treatment of periodontitis: how many options for one disease? Periodontol 2000 2017;75:152-88

[134] Nibali L,Koidou VP,Nieri M,Barbato L,Pagliaro U,Cairo F. Regenerative surgery versus access flap for the treatment of intra-bony periodontal defects: a systematic review and meta-analysis J Clin Periodontol 2020 47 320 51

[135] Gao H,Yin S,Yan Y.et al. Inhibitory effect of Allium cepa L.-derived extracellular vesicles loaded with celecoxib on osteoclast differentiation in periodontitis Int J Nanomedicine 2026 21 580087 PMC13112040

[136] Kürtösi B,Kazsoki A,Zelkó R. A systematic review on plant-derived extracellular vesicles as drug delivery systems Int J Mol Sci 2024 25 7559 PMC11277065

[137] Wei X,Wang M,Dong X.et al. Internal-external homologous drug-loaded exosome-like nanovesicles released from semi-IPN hydrogel enhancing wound healing of chemoradiotherapy-induced oral mucositis Int J Nanomedicine 2025 20 4105 21 PMC11977572

[138] Hearnden V,Sankar V,Hull K.et al. New developments and opportunities in oral mucosal drug delivery for local and systemic disease Adv Drug Deliv Rev 2012 64 16 28

[139] Benoit DSW, Sims KR Jr, Fraser D. Nanoparticles for oral biofilm treatments ACS Nano 2019 13 4869 75 PMC6707515

[140] Liu L,Wu D,Tu H.et al. Applications of hydrogels in drug delivery for oral and maxillofacial diseases Gels 2023 9 146 PMC9956178