Development of Oral Mucosal Organoid for Oral Disease Modeling and Management: A Review
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Abstract
Monolayer cultures and animal models face limitations in accurately evaluating cellular oral mucosal behavior. Oral disease modeling using tissue-engineered oral mucosa replicates the complexity of human tissue, offering improved opportunities for studying molecular mechanism. Therefore, it is important to highlight recent developments in oral mucosal organoids in wound healing, carcinogenesis, and other investigation models. This review article performed a literature search and carefully selected and summarized articles from PubMed and Scopus data base to get information on oral mucosal organoids in various fields. The keywords were: “organotypic” OR “organoid” OR “3D” AND “oral mucosa” AND “model”. The search yielded 31 articles on oral mucosal organoids, which addressed various cell sources, scaffolds and techniques that can be applied to develop organoids to elucidate a certain mechanism of action. Enhancement in extracellular matrix properties and incorporation of immune and/or other oral cells could provide better understanding of oral mucosa molecular responses.
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Koskinen Holm C, Qu C, Holm CK, Qu C. Engineering a 3D In Vitro Model of Human Gingival Tissue Equivalent with Genipin/Cytochalasin D. Int J Mol Sci. 2022;23(13):7401. doi:10.3390/ijms23137401.
Rodrigues Neves C, Buskermolen J, Roffel S, Waaijman T, Thon M, Veerman E, et al. Human saliva stimulates skin and oral wound healing in vitro. J Tissue Eng Regen Med. 2019;13(6):1079-92. doi:10.1002/term.2865.
Buskermolen JK, Janus MM, Roffel S, Krom BP, Gibbs S. Saliva-Derived Commensal and Pathogenic Biofilms in a Human Gingiva Model. J Dent Res. 2018;97(2):201-8. doi:10.1177/0022034517729998.
de Carvalho Dias K, de Sousa DL, Barbugli PA, Cerri PS, Salih VM, Vergani CE. Development and characterization of a 3D oral mucosa model as a tool for host-pathogen interactions. J Microbiol Methods. 2018;152:52-60. doi:10.1016/j.mimet.2018.07.004.
Sobue T, Bertolini M, Thompson A, Peterson DE, Diaz PI, Dongari-Bagtzoglou A. Chemotherapy-induced oral mucositis and associated infections in a novel organotypic model. Mol Oral Microbiol. 2019;33(3):212-23. doi:10.1111/omi.12214.Chemotherapy-induced.
Joseph JF, Gronbach L, García-Miller J, Cruz LM, Wuest B, Keilholz U, et al. Automated Real-Time Tumor Pharmacokinetic Profiling in 3D Models: A Novel Approach for Personalized Medicine. Pharmaceutics. 2020;12(5):413. doi:10.3390/pharmaceutics12050413.
Choi S-Y, Kang SH, Oh SY, Lee KY, Lee HJ, Gum S, et al. Differential Angiogenic Potential of 3-Dimension Spheroid of HNSCC Cells in Mouse Xenograft. Int J Mol Sci. 2021;22(15):8245. doi:10.3390/ijms22158245.
Shaikh ZN, Alqahtani A, Almela T, Franklin K, Tayebi L, Moharamzadeh K. Effects of electronic cigarette liquid on monolayer and 3D tissue-engineered models of human gingival mucosa. J Adv Periodontol Implant Dent. 2019;11(2):54-62. doi:10.15171/japid.2019.010.
Binaljadm T, Moorehead R, Almela T, Franklin K, Tayebi L, Moharamzadeh K. Biomodification of a class-v restorative material by incorporation of bioactive agents. Dent J. 2019;7(4):110. doi:10.3390/DJ7040110.
Gronbach L, Jurmeister P, Schäfer-Korting M, Keilholz U, Tinhofer I, Zoschke C. Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models. Front Bioeng Biotechnol. 2020; 8:579896. doi:10.3389/fbioe.2020.579896.
Sakulpaptong W, Clairmonte IA, Blackstone BN, Leblebicioglu B, Powell HM. 3D engineered human gingiva fabricated with electrospun collagen scaffolds provides a platform for in vitro analysis of gingival seal to abutment materials. PLoS One. 2022;17(2):e0263083. doi:10.1371/journal.pone.0263083.
Driehuis E, Oosterom N, Heil SG, Muller IB, Lin M, Kolders S, Jansen G, et al. Patient-derived oral mucosa organoids as an in vitro model for methotrexate induced toxicity in pediatric acute lymphoblastic leukemia. PLoS One. 2020;15(8):e0237488. doi:10.1371/journal.pone.0237488.
Wagner T, Beer L, Gschwandtner M, Eckhart L, Kalinina P, Laggner M, et al. The Differentiation-Associated Keratinocyte Protein Cornifelin Contributes to Cell-Cell Adhesion of Epidermal and Mucosal Keratinocytes. J Invest Dermatol. 2019;139(11):2292-301.e9. doi:10.1016/j.jid.2019.04.019.
Xu H, Sobue T, Bertolini M, Thompson A, Vickerman M, Nobile CJ, et al. S. oralis activates the Efg1 filamentation pathway in C. albicans to promote cross-kingdom interactions and mucosal biofilm. Virulence. 2017;8(8):1602-17. doi:10.1111/jre.1292715.
Krishnamoorthy AL, Lemus AA, Solomon AP, Valm AM, Neelakantan P. Interactions between Candida albicans and Enterococcus faecalis in an Organotypic Oral Epithelial Model. Microorganisms. 2020;8(11):1771. doi:10.3390/microorganisms8111771.
Shang L, Deng D, Buskermolen JK, Roffel S, Janus MM, Krom BP, et al. Commensal and Pathogenic Biofilms Alter Toll-Like Receptor Signaling in Reconstructed Human Gingiva. Front Cell Infect Microbiol. 2019;9: 282. doi:10.3389/fcimb.2019.00282.
Shang L, Deng D, Buskermolen JK, Janus MM, Krom BP, Roffel S, et al. Multi-species oral biofilm promotes reconstructed human gingiva epithelial barrier function. Sci Rep. 2018;8(1):16061. doi:10.1038/s41598-018-34390-y.
Gould SJ, Foey AD, Salih VM. An organotypic oral mucosal infection model to study host-pathogen interactions. J Tissue Eng. 2023;14:20417314231197310. doi: 10.1177/20417314231197310.
Sobue T, Bertolini M, Thompson A, Dongari-Bagtzoglou A. Model of Chemotherapy-associated Mucositis and Oral Opportunistic Infections. Bio-Protocol. 2019;9(21):e3411. doi:10.21769/bioprotoc.3411.
Battaglia A, Nguyen T. Transmucosal Delivery of Nicotine in Combination with Tincture of Benzoin Inhibits Apoptosis. Drugs R D. 2017;17(4):615-21. doi:10.1007/s40268-017-0212-x.
Konstantinova V, Ibrahim M, Lie SA, Birkeland ES, Neppelberg E, Marthinussen MC, et al. Nano-TiO(2) penetration of oral mucosa: in vitro analysis using 3D organotypic human buccal mucosa models. J oral Pathol Med Off Publ Int Assoc Oral Pathol Am Acad Oral Pathol. 2017;46(3):214-22. doi:10.1111/jop.12469.
Leano SM, De Souza W, De Vecchi R, Lopes A, Deliberador T, Granjeiro JM. A multimodal in vitro approach to assess the safety of oral care products using 2D and 3D cellular models. Front Toxicol. 2024;6:1474583. doi: 10.3389/ftox.2024.1474583.
Dommisch H, Stolte KN, Jager J, Vogel K, Müller R, Hedtrich S, et al. Characterization of an ester-based core-multishell (CMS) nanocarrier for the topical application at the oral mucosa. Clin Oral Investig. 2021;25(10):5795-805. doi:10.1007/s00784-021-03884-x.
Pimentel BNA da S, Marin-Dett FH, Assis M, Barbugli PA, Longo E, Vergani CE. Antifungal Activity and Biocompatibility of α-AgVO3, α-Ag2WO4, and β-Ag2MoO4 Using a Three-Dimensional Coculture Model of the Oral Mucosa. Front Bioeng Biotechnol. 2022;10: 826123. doi:10.3389/fbioe.2022.826123.
Hoque Apu E, Akram SU, Rissanen J, Wan H, Salo T. Desmoglein 3 – Influence on oral carcinoma cell migration and invasion. Exp Cell Res. 2018;370(2):353-64. doi:10.1016/j.yexcr.2018.06.037.
Roffel S, Wu G, Nedeljkovic I, Meyer M, Razafiarison T, Gibbs S. Evaluation of a novel oral mucosa in vitro implantation model for analysis of molecular interactions with dental abutment surfaces. Clin Implant Dent Relat Res. 2019;21(S1):25-33. doi:10.1111/cid.12750.
Barker E, AlQobaly L, Shaikh Z, Franklin K, Moharamzadeh K. Implant soft-tissue attachment using 3D oral mucosal models—A pilot study. Dent J. 2020;8(3):72. doi:10.3390/DJ8030072.
Perduns R, Volk J, Plum M, Jochums A, Gutzki F, Kaever V, et al. Camphorquinone alters the expression of extracellular proteases in a 3D co-culture model of the oral mucosa. Dent Mater. 2021;37(2):236-248. doi: 10.1016/j.dental.2020.11.005.
Alamo L, Cassiano FB, Bordini EAF, Stuani VT, Pacheco LE, Gallinari MO, et al. An organotypic model of oral mucosa cells for the biological assessment of 3D printed resins for interim restorations. J Prosthet Dent. 2024 Jul;132(1):251-259. doi: 10.1016/j.prosdent.2022.04.017.
Blanco-Elices C, Chato-Astrain J, Oyonarte S, Bermejo-Casares F, España-López A, Fernández-Valadés R, et al. Generation of a novel model of bioengineered human oral mucosa with increased vascularization potential. J Periodontal Res. 2021;56(6):1116-31. doi:10.1111/jre.12927.
Ollington B, Colley HE, Murdoch C. Immunoresponsive Tissue-Engineered Oral Mucosal Equivalents Containing Macrophages. Tissue Eng - Part C Methods. 2021;27(8):462-71. doi:10.1089/ten.tec.2021.012428.