Ramis JM*1,2, Llopis-Grimalt MA1,2, Munar-Bestard M1,2 and Monjo M1,2
Received: February 12, 2018; Published: February 19, 2018
*Corresponding author: Joana Maria Ramis Morey, Group of Cell Therapy and Tissue Engineering, Research Institute on Health Sciences (IUNICS), University of Balearic Islands, Ctra Valldemossa, Palma, Spain
Monolayer cultures ofepithelial or gingival fibroblasts have been used for the study of oral mucosa and the effect of external stimuli, such as different types of dental materials. However, monolayer models lack polarized cell phenotype and systemic components, which affect their function and response to stimuli [1,2]. Several tissue-engineered oral mucosa models have been developed to overcome these limitations with applications in different fields . These 3D cultures provide a higher degree of complexity than monolayer cell cultures being closer to explant cultures, providing an in vitro model resembling the in vivo situation . At least two tissue-engineered oral mucosa models are commercially available, SkinEthicTMOral Epithelium and Gingival Epithelium constructs from EPISKIN (Lyon France), or the Epi OralTM and Epi GingivalTM constructs from Mat Tek Corporation (Ashland, MA, USA). Other commercial skin tissue models are validated to be used as an alternative to animal testing to proof cosmetics safety . Thus it could be envisaged that in the near future oral tissue models might be approved to test cosmetic dental raw materials or formulations such as tooth pastes or mouthwashes. However, the existing commercial models lack a fibroblast/collagen matrix component, which is critical in human oral mucosa .
In order to produce a full thickness tissue-engineered mucosa with epithelial and fibroblasts components, several strategies have been followed using different scaffolds or cells from different origin (Table 1). These differences in scaffold and cell origin are very important depending on the aim of the study or the application of the oral system. In vivo clinical applications include both intraoral graftings (i.e., for use in reconstructions of the oral cavity after tumor resection or the treatment of gingival recession) and extra-oral applications (i.e., for use in urethoplasty, grafting of burn wounds or eyelid reconstruction) [1,6]. For these applications, human primary cells (from the same patient if possible) are used in the fabrication of the oral graft . Besides, in vitro applications include cosmetic testing or study of different dental materials such as titanium implants . These 3D cultures can also be used in oral cancer research to facilitate the study of mechanistic aspects of the disease, early invasion, tumor growth, new treatments or diagnostic tests . For in vitro applications, the use of immortalized cells is preferred, since primary cells are difficult to maintain for a long period of time and results can differ for every cell donor. Buccal carcinoma cell lines may not represent normal epithelial cells; since the results produced using these cells should be interpreted with caution and validated with other cells . Another in vitro application is the use of tissue-engineered oral mucosa as model for the emerging research field that studies soft tissue interaction with dental implant abutments. Human primary oral keratinocytes and human primary oral fibroblasts have been used to produce constructs for this purpose [9,10]. In addition, a three-dimensional tissue engineered bone-oral mucosal model has been produced to asses both soft and hard tissue integration on titanium implants .
Table 1: Summary of different strategies (scaffolds and cell types) used to develop tissue-engineered oral mucosa.
In conclusion, here we have summarized the different strategies that are being evaluated to develop tissue-engineered oral mucosa and its different applications.
This work was supported by the Ministerio de EducacionCultura y Deporte (contract to M.A.L.G; FPU15/03412), the Instituto de Salud Carlos III (contract to J.M.R; CP 16/00124,) and the Ministerio de Empleo y Seguridad Social with the Sistema de GarantiaJuvenil (contract to M.M.B).