Kubilus, J., Klausner, M., Breyfogle, B. MatTek Corporation, Ashland, MA.

The development of human reconstructed tissues of the oral cavity that express in vivo-like differentiated characteristics would be important to better understand and develop therapies for gum disease, oral cancer, lesions due to smokeless tobacco, and gingivitis, amongst other diseases of the oral mucosa. In vitro tissue models would be used to assess the biocompatibility of new dental materials, dentifrices, and oral care consumer products, the delivery of pharmaceuticals through the oral mucosa, and the possible HIV infection thereof. To meet these needs, MatTek scientists have recently developed EpiOral™, a tissue culture model of the oral epithelium. Gingival cells were harvested from tissue explants, expanded in monolayer culture, and induced to form a three-dimensional tissue using serum free medium. Histologically, the EpiOral tissues are 8-12 cells layers thick with cells becoming increasingly squamous as the apical surface is approached. This tissue most closely resembles the non-cornified buccal (inner cheek) tissue of the oral cavity. The EpiOral tissues are cultured in easily manipulated cell culture inserts and the tissues extend from wall-to-wall. In terms of ease of use, these characteristics greatly facilitate testing of oral care products in that direct topical application is possible. To assess the reproducibility of the EpiOral tissue, the tissues were exposed to the common surfactant, 1% Triton X-100 (TRI), and viability dose response curves were constructed using the MTT assay. An Effective Time-50 (ET50), i.e. the time of exposure after which viability is reduced to 50%, was determined. The ET50 for 3 lots of tissue averaged 112 ± 12.7 minutes. In terms of resistance to surfactant injury by TRI, the gingival tissue is more susceptible to damage compared with the EpiDerm™ skin model (ET50 = 6.74 ± 0.99 hrs), but more robust than the EpiOcular™ tissue model (ET50= 24.9 ± 6.3 mins). Exposure to sensitive and normal strength dentifrices showed that viability of the tissue was compromised to a greater degree by the normal strength toothpastes. Based on these initial results, further investigation of the EpiOral tissue model’s ability to predict potential gingival irritation from oral care products is warranted.


Buccal, Dental, Dentifrice, Drug delivery, EpiOral, Gingival, Gingivitis, Gum disease, Oral, Oral cancer, Oral mucosa, Smokeless tobacco, Transmucosal drug delivery

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