Revista nº 813

Artificial oral mucosa | Ibáñez Cortés M, et al. Actual Med. 2021; 106(813): 177- 187 184 proliferative basal cells markers as CKs 5 and 14 stratification and maduration of epithelial layer using CKs 4 and 13 markers, keratinization using markers as CKs 3, 10 and 12. According to the findings of the literature, to include a extended pool of cytokeratins will be helpful to classify the type artificial oral mucosa developed by tissue engineering (10,15,22- 24). Three groups, Garzón et al, Nishiyama et al and Almela et al , have used antibodies for the detection of cytokeratins associated with proliferative basal cells, stratification and keratinization (34-37). In contrast, numerous research groups have only describe CKs expression for one or two markers of proliferative basal cells, stratification or keratinization (38-48). However, Iida et al have not used any epithelial markers to characterize oral mucosa epithelium (49). Furthermore, most of the artificial oral mucosa developed by tissue engineering have shown stratification and maduration of the epithelial tissue according to the positive expression of CK 4 and 13, both, present in suprabasal layers of epithelia (34-42,44,45,47,48). According to the cytokeratin expression profile, oral mucosa substitutes produced by Qi et al , Izumi et al, Bayar et al, Lauer et al and Almela et al could be classified as keratinized mucosa (34,39,44,46). Moreover, substitutes developed by Garzón et al and Sánchez- Quevedo et al are classified as non-keratinized mucosa (35,36,47). Nishiyama et al produced both types in their study (37). According to the review of the literature, the scarce amount of cytokeratins used to characterize epithelium in artificial oral mucosa developed by tissue engineering may limit the possibility to classify the specific type of oral mucosa with the anatomical site. Nevertheless, there are few groups that produced artificial oral mucosa which can be classified as specific of an oral cavity area. Oral mucosa of Lauer et al , Garzón et al and Alaminos et al could be specific for gingiva but the lack of expression of CK 10 in artificial oral mucosa developed by Garzón et al and Alaminos et al should mimick in a better way the expression profile of the mouth’s floor. In addition, the oral mucosa of Garzón et al could be used for soft palate repair while the oral mucosa of Alaminos et al could be used for lips and dorsal tongue repair (35,36,38,44 ) . Surprinsingly, oral mucosa substitutes developed by Garzón and collaborators did not show keratinized cytokeratins expression in vitro but when the engineered tissue was implanted in athymic mice the expression pattern changed starting to express CK 10 (35,36). This finding point out the importance of in vitro and in vivo characterization of artificial oral mucosa. One of the main challenges in the field of bioengineered oral mucosa is to reproduce in vitro an artificial oral mucosa with the same epithelial characteristics of the specific injured anatomical area (34-49). To achive this, future studies should be focused in the histological characterization of the different anatomical areas of native oral mucosa in order to stablish the minimal criteria to develop artificial oral mucosa of specific anatomical areas. The last challenge in oral mucosa tissue engineering will be to produce vascularized artificial oral mucosa to ensure that post-implanted tissue will be linked to the human capillaries by anastomosis enhancing the graft survival of bioengineered tissue (50). The knowledge of the main anatomical and histological features of the native human oral mucosa is essential for the fabrication of human oral mucosa substitutes. In this sence, the development of tailored-oral mucosa substitutes should require the deep characterization of cytokeratins expression profile in order to achive the main characteristics of each type of oral mucosa in the oral cavity. In addition, the evidence that in vivo enviroment tend to modified the cytokeratin expression pattern is enough reason to reccomend in vivo testing of newly-produce oral mucosa substitutes. 1. Souza LR, Oliveira MM, Basile JR, Souza LN, Souza ACR, Haikal DS, et al. Anatomical and Physiopathological As- pects of Oral Cavity and Oropharynx Components Related to Oropharyngeal Dysphagia. IntechOpen: Rijeka; 2015. DOI: 10.5772/60766 2. Kinikoglu B, Damour O, Hasirci V. Tissue engineering of oral mucosa: a shared concept with skin. J Artif Organs. 2015;18(1):8-19. DOI: 10.1007/s10047-014-0798-5 3. Mackenzie IC, Binnie WH. Recent advances in oral mucosal research. J Oral Pathol. 1983;12(6):389-415. DOI: 10.1111/ j.1600-0714.1983.tb00353.x 4. Garzón I. Estudio de marcadores de diferenciación epitelial en mucosa oral construida por ingeniería tisular: Universi- dad de Granada; 2009. 5. Gómez ME, Campos A. Histología y embriología bucoden- tal: bases estructurales de la patología, el diagnóstico, la terapeutica y la prevención odontológica. Panamericana: Madrid; 2002. FUTURE PERSPECTIVES CONCLUSION BIBLIOGRAPHIC REFERENCES