Feasibility of a porcine oral mucosa equivalent: A preclinical study
Oral tissue engineering aims to treat and fill tissue deficits caused by congenital defects, facial trauma, or malignant lesion surgery, as well as to study the biology of oral mucosa. The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require a large animal model to evaluate cell-based devices, including tissue-engineered oral mucosa, prior to initiating human clinical studies. Porcine oral mucosa is non-keratinized and resembles that of humans more closely than any other animal in terms of structure and composition; however, there have not been any reports on the reconstruction of a porcine oral mucosa equivalent, probably due to the difficulty to culture porcine fibroblasts. In this study, we demonstrate the feasibility of a 3D porcine oral mucosa equivalent based on a collagen-GAG-chitosan scaffold, as well as reconstructed porcine epithelium by using an amniotic membrane as support, or without any support in form of epithelial cell sheets by using thermoresponsive culture plates. Explants technique was used for the isolation of the porcine fibroblasts and a modified fibroblast medium containing 20% fetal calf serum was used for their culture. The histological and transmission electron microscopic analyses of the resulting porcine oral mucosa models showed the presence of non-keratinized epithelia expressing keratin 13, the major differentiation marker of non-keratinized oral mucosa, in all models, and the presence of newly synthesized collagen fibers in the lamina propria equivalent of the full-thickness model, indicating the functionality of porcine fibroblasts.
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- "e l s e v i e r . c o m / l o c a t e / p h a s c i primates (Collins et al., 1981; Kinikoglu et al., 2012; Shabana et al., 1989). These advantages suggest the selection of large animal species for animal models for the evaluation of cell-based devices (Moharamzadeh et al., 2012). "
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ABSTRACT: Several animals have been used as models for basic and clinical research on oral mucosa. Few studies have focused on the selection of an appropriate animal model. This study aimed to provide histological references for selecting a potential model. Histological features were assessed by exploring 6 morphological characteristics and 2 immunohistochemical markers. The morphological characteristics included keratinization, basal membrane appearance, epithelial thickness, rete ridge length, adjacent rete ridge distance, and regional variation; the immunohistochemical markers included Ki67 (a proliferative marker) and Cytokeratin19 (CK19; a stemness marker). The histological similarity of each species compared to humans was calculated according to the designated scoring criteria. The results showed that the buccal mucosae from dog and pig were non-keratinized, with similar rete ridge length and distance, compared to that of humans. The dog, rat, and cavy mucosae had analogous gross appearances in the basal membrane. The dog oral mucosae shared similar epithelial thickness with human oral mucosae. Compared to the human mucosa, the dog, pig, rat, and rabbit mucosae exhibited corresponding regional variations. The Ki67-positive cells in human and canine mucosae were predominantly localized in the suprabasal layers, whereas most of the proliferative cells were in the basal layer in other species. CK19 immunoreactivities were detected only in human and canine mucosae. The canine mucosae gained the highest point value (14), whereas the scores for the pig, rat, rabbit, cavy, sheep, and buffalo mucosae were 8, 6, 5, 5, 5, and 2, respectively. The histological variations in the oral epithelium of diverse animal species are considerable; the mucosae from dogs are most similar to human mucosae, implicating its histological basis as an animal model.
European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 10/2015; 81. DOI:10.1016/j.ejps.2015.09.019 · 3.35 Impact Factor
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ABSTRACT: Tissue-engineered oral mucosa, in the form of epithelial cell sheets or full-thickness oral mucosa equivalents, is a potential solution for many patients with congenital defects or with tissue loss due to diseases or tumor excision following a craniofacial cancer diagnosis. In the laboratory, it further serves as an in vitro model, alternative to in vivo testing of oral care products, and provides insight into the behavior of the oral mucosal cells in healthy and pathological tissues. This review covers the old and new generation scaffold types and materials used in oral mucosa engineering; discusses similarities and differences between oral mucosa and skin, the methods developed to reconstruct oral mucosal defects; and ends with future perspectives on oral mucosa engineering.
Journal of Artificial Organs 10/2014; 18(1). DOI:10.1007/s10047-014-0798-5 · 1.44 Impact Factor
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