Zwicker Paula, Zumpe Maxi, Kramer Axel, Müller Gerald
Institute of Hygiene and Environmental Medicine, University Medicine, Ferdinand-Sauerbruch-Straße, D-17475 Greifswald, Germany.
Department of Pediatric Hematology and Oncology, University Medicine, Ferdinand-Sauerbruch-Straße, D-17475 Greifswald, Germany.
Pharmaceutics. 2023 Feb 21;15(3):721. doi: 10.3390/pharmaceutics15030721.
Oral mucositis is the most common and severe non-hematological complication associated with cancer radiotherapy, chemotherapy, or their combination. Treatment of oral mucositis focuses on pain management and the use of natural anti-inflammatory, sometimes weakly antiseptic mouth rinses in combination with optimal oral cavity hygiene. To prevent negative effects of rinsing, accurate testing of oral care products is necessary. Due to their ability to mimic realistic in-vivo conditions, 3D models may be an appropriate option in compatibility testing of anti-inflammatory and antiseptically effective mouth rinses. We present a 3D model of oral mucosa based on the cell line TR-146 with a physical barrier, characterized by high transepithelial electrical resistance (TEER) and confirmed cell integrity. Histological characterization of the 3D mucosa model showed a stratified, non-keratinized multilayer of epithelial cells similar to that of human oral mucosa. By means of immuno-staining, tissue-specific expression of cytokeratin 13 and 14 was shown. Incubation of the 3D mucosa model with the rinses had no effects on cell viability, but TEER decreased 24h after incubation in all solutions except ProntOral. Analogous to skin models, the established 3D model meets the quality control criteria of OECD guidelines and may therefore be suitable for comparing the cytocompatibility of oral rinses.
口腔黏膜炎是与癌症放疗、化疗或放化疗联合治疗相关的最常见且最严重的非血液学并发症。口腔黏膜炎的治疗重点在于疼痛管理以及使用天然抗炎、有时兼具弱防腐作用的漱口水,并结合最佳口腔卫生措施。为防止漱口水产生负面影响,有必要对口腔护理产品进行准确测试。由于3D模型能够模拟真实的体内条件,因此在抗炎和具有防腐效果的漱口水兼容性测试中,它可能是一个合适的选择。我们展示了一种基于TR-146细胞系构建的具有物理屏障的口腔黏膜3D模型,其特征为高跨上皮电阻(TEER)且细胞完整性得到确认。该3D黏膜模型的组织学特征显示出与人类口腔黏膜相似的分层、非角化多层上皮细胞。通过免疫染色,显示了细胞角蛋白13和14的组织特异性表达。用漱口水孵育3D黏膜模型对细胞活力没有影响,但除ProntOral外,在所有溶液中孵育24小时后TEER均下降。与皮肤模型类似,所建立的3D模型符合经合组织指南的质量控制标准,因此可能适用于比较漱口水的细胞相容性。