Feasibility of a porcine oral mucosa equivalent: a preclinical study.
ABSTRACT 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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ABSTRACT: The projected annual demand for stem cell-based dental treatments in the United States can range from over 290 million tooth restorative treatments to 30,000 patients requiring tissue regeneration following craniofacial cancer surgery. Professional dental treatments cost Americans over $60 billion per year. Scientific advances in stem cell technologies, tissue engineering, and transplantation will provide the basis for the introduction of new treatment technologies into dentistry. This review provides an assessment of how stem cell therapies will likely change dental practice. The problems of introducing stem cell therapies are substantial, but they provide the best hope for many patients with congenital defects, and to regenerate teeth and tissues lost because of disease, cancer, and trauma, or missing because of congenital malformation. The most expensive dental treatments may be the most attractive candidates for stem cell therapies. This would indicate that craniofacial reconstruction, implants, and endodontic treatments are the most valuable applications of dental stem cell therapies, whereas tooth restorations and other dental treatments are the less commercially valuable.Stem Cells and Development 01/2007; 15(6):881-7. · 4.67 Impact Factor
- Journal of Oral and Maxillofacial Surgery 11/2005; 63(10):1418-25. · 1.28 Impact Factor
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ABSTRACT: The main objective of this publication is to make the reader aware of the complexity and steps that are necessary to make a Food and Drug Administration (FDA)-approved laboratory produced cell-based device, for use in clinical trials for reconstructive surgery. Most tissue-engineered cell-based devices are considered as 'human somatic cell therapy' and fall under the auspices of the Center of Biologic Evaluation and Research (CBER) and are considered a combination product by the FDA. We have illustrated the algorithm that is necessary to follow an Independent New Drug (IND) application by using our ex vivo produced oral mucosa equivalents (EVPOME), a tissue-engineered oral mucosa, as an example of a cell-based device that needs FDA approval prior to clinical application. By illustrating the experimental approach and presenting resulting data we attempt to explain each step that we address along the way.Cells Tissues Organs 02/2004; 176(1-3):134-52. · 1.96 Impact Factor