组织工程化口腔黏膜中应力推挤角化细胞移位形成上皮钉突样结构的研究

项目名称： 组织工程化口腔黏膜中应力推挤角化细胞移位形成上皮钉突样结构的研究

项目编号： No.81201213

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 熊学鹏

作者单位： 武汉大学

项目金额： 23万元

中文摘要： 当前构建的组织工程化口腔黏膜多缺乏上皮钉突样结构，临床应用时其上皮细胞层易与支架分离。本课题组前期的研究提示：在外界应力刺激下，口腔黏膜上皮棘细胞层中瞬时增殖细胞分裂增殖加速，产生的内应力推挤基底层干细胞向黏膜固有层移位，同时分泌MMP降解细胞外基质，上皮钉突由此形成，ERK、AKT和PC等信号通路参与其间的调控。 本课题拟通过加压载荷、基因转染等技术，在体外模拟上皮钉突形态发生过程中的细胞生物学事件，构建含上皮钉突样结构的组织工程化口腔黏膜。研究内容包括：①角化细胞内ERK、AKT和PC等信号通路中关键因子的表达水平与细胞内应力大小的关联；②加压载荷条件下，将转染有erk、akt和pc等基因的角化细胞用于构建组织工程化口腔黏膜；③组织工程化口腔黏膜回植至SCID鼠腭部的研究。 本研究构建的组织工程化口腔黏膜可能具有上皮钉突样结构，为增进其上皮细胞层与支架之间的粘附力提供新的解决方法。

中文关键词： 口腔黏膜；组织工程；上皮钉突形态发生；应力；ERK1/2

英文摘要： The current fabricated tissue engineered oral mucosa equivalents usually lack rete ridges, and their epidermis are apt to detach from the scaffold after clinical application. Our previous research suggested mechanical stresses stimulated the proliferation of the transient amplifying cells,and it produced inner stresses that pushed the neighbor basal keratinocytes migration towards the lamina propria, while the extracellular matrix was degraded by the simultaneously secreted MMPs, herein, the rete ridge has been formed, and ERK, AKT and PC cascades played important roles in these processes. This project aims to fabricate a tissue engineered oral mucosa equivalent which endowed with rete ridge-like structure, the employed resolution is to simulate the cellular and biological processes of rete ridge morphogenesis in vitro. This project has 3 parts: ⅰ)The correlation between the expression level of the key factors in the ERK, AKT, PC cascades and the produced inner stresses of the oral keratinocytes.ⅱ) To construct a tissue engineered oral mucosa equivalent with genes transfected keratinocytes under stresses loading circumstance. ⅲ)In vivo transplantation of the tissue engineered oral mucosa equivalents onto the palatal wounds of the SCID mice. Our fabricated tissue engineered oral mucosa equivalents will have rete

英文关键词： oral mucosa；tissue engineering；rete ridge morphogenesis；stress；ERK1/2