Revista nº 813

Artificial oral mucosa | Ibáñez Cortés M, et al. Actual Med. 2021; 106(813): 177- 187 178 However, the scarce number of oral mucosa donors and the associated drawbacks to the surgical technique, dramatically increase the need of artificial oral mucosa susbtitutes developed by tissue engineering. In this mileu, several oral mucosa models have been produced by tissue engineered varying from models formed by one or more keratinocytes layers mimicking epithelial tissue until full-thickness models consisting of keratinocytes layers and a connective tissue formed by fibroblasts making use of different commertial (ie, Matriderm®) or non-commertial (ie, fibrin-agarose) scaffolds (4,8,9). Most of the patients can suffer lesions in the different areas of the oral cavity as gingiva, hard and soft palates, mouth’s floor, lips, cheeks, ventral and dorsal tongue, taste papillae or lingual tonsil. Each anatomical area have been associated to specific histological characteristics, as number of epithelial layers, cytokeratin expression profile of epithelial keratinocytes and type of connective tissue which can be lax, semidense or dense (5,10). In this regard, the generation of artificial substitutes includes standarized oral mucosa with random characteristics for the replacement of injuries in oral cavity without attending to the histological differences of each anatomical area. In the present work, we have revised previously published data regarding the main histological features of oral mucosa from different anatomical areas of the oral cavity in order to develop in the future a histological-tailored artificial oral mucosa. In other words, the future artificial substitute will keep the same histological characteristics that the injured area of the oral cavity which has to be repaired. EPITHELIAL TISSUE The epithelial tissue offers a structural barrier that protects against the mechanical forces, the entry of external substances or microorganisms and the lost of fluids (2). The main cells of epithelium are the keratinocytes (90% of the total epithelial cell) while the rest is divided between permanent cells as melanocytes, Langerman and Merkel cells (9%) and transitory cells as granulocytes, limphocytes and monocytes (1%). Keratinocytes are responsable for creating all epithelial strata (basal and suprabasal layers), migrating from the deepest stratum to the most superficial and getting keratinizated in this migration process (4,5). Basal layer is formed by keratinocytes with round nucleus that are in continuous division to ensure self-renovation of the epithelial tissue. Adjacent to this layer, spinous layer is composed by different layers of poligonal keratinocytes that are linked due to the presence of desmosomes-associated proteins and tonofilaments. Subsequently, granular layer is formed by squamous cells with small nucleus where keratohyaline granules and Odland’s bodies are found. The most superficial layer is mainly composed by anucleate cells with wide expression of involucrin and filaggrin as key markers of maturation. In this context, attending to the grade of keratinocytes maduration and the anatomical location, three types of stratified epithelium can be observed in the oral cavity: i) orthokeratinizated where nuclei in the most superficial layer are absent, ii) parakeratinized where nuclei in the most superficial layer are pyknotic and iii) nonkeratinizated epithelia where there is not this superficial layer (4,5,11-15). BASEMENT MEMBRANE Epithelial and connective tissue have a permanent crosstalk due to the presence of the basementmembrane. The main function of the basement membrane is to serve as a barrier for the pass of negative charges and act as guide of celular migration in the process of wound reepithelization (4,5). Basement membrane is composed by a basal lamina and reticular lamina. The basal lamina is synthesized by epithelial cells mainly composed of integrins, laminin 5, entactin, heparin sulfate, collagen IV, fibronectin among other proteins. The reticular lamina is synthesized by connective cells with the presence of glucosaminoglycan matrix and two types of fibers: i) anchor fibers of collagen VII and ii) reticular fibers as reticulin (trimeric collagen III) (15-17). CONNECTIVE TISSUE AND SUBMUCOSA The connective tissue of the native human oral mucosa can be lax, dense or semidense according to the anatomical location into the oral cavity. The key function of the connective tissue is to serve as nutritional support to the epithelium. The connective tissue cell population are mainly composed by fibroblasts, macrophages, lymphocytes, mast cells and plasmatic cells (4,5). Fibroblasts produce the fibrillar and non-fibrillar extracellular matrix as collagen I and VI, elastic fibers (elastin), reticular fibers (reticulin), proteoglycans (hyaluronic acid, heparin sulphate, syndecan, decorin) and glycoproteins (fibronectin, tenascin). Two zones are clearly defined in the connective tissue, the papillary layer and reticular layer. The papillary layer have a closed relation with epithelial rete ridges increasing the junction of both tissues and facilitating the exchange between epithelium and blood vessels. Apart from papillary layer, the reticular layer is located subjacent to the papillary layer and is rich in fibrilar components of the extracellular matrix (5,12,15,17, 8). Finally, connective tissue is linked to submucosa which is composed by lax connective tissue linked to subjacent tissues. The submucosa can be well-developed in areas exposed to masticatory forces or directly scarce in areas where there is rare movement. In addition, salivary glands, blood vessels, nerves and adipose tissue can be found in the submucosa (5,12,13,16,18). HISTOLOGY OF NATIVE HUMAN ORAL MUCOSA