The objective of this proposed research is to develop an intestinal cell culture substrate to improve the accuracy of in vitro drug transport studies and provide a scaffold for intestinal tissue regeneration. A culture substrate that exactly mimics the natural topography of intestinal basement membrane will be developed, providing essential developmental cues to cells cultured in vitro. Chemical vapor deposition (CVD) will be used to create a silica template of intestinal basement membrane that exactly mimics the native nano- and micro-topography. CVD will be used to caoat the silica mold with a porous biocompatible polymer such as poly(2-hydroxyethyl methacrylate) (pHEMA). This polymer substrate will be separated from the silica mold and used for cell culture. SEM will be used to characterize the silica and pHEMA topology and compare it to native issue. The influence of the topography of the developed device on enterocyte cell phenotype and transport properties will be compared with cells cultured on non-topographically modified surfaces via a variety of assays.
This work will result in the development of a cell-based tool for studying transport across the intestinal epithelium, leading to cost and time savings in drug studies, as well as a fundamental understanding of cell-biomaterial interactions and native intestinal function in normal and disease (e.g. colon cancer) states. If successful, this research will significantly reduce the time and development costs for bringing pharmaceuticals to market, as well as make serious contributions to the treatment of numerous intestinal illnesses, including short bowel syndrome, Crohn's disease, and colon cancer. It offers a greatly improved approach to current cell culture techniques through the creation of culture substrates that exactly mimic important features found in vivo, and provides basic scientific insight into the influence of nano- and micro-topography on enterocyte phenotype.
