(722bb) Replication of Intestinal Basement Membrane Via Chemical Vapor Deposited Silica Thin Films

Cell culture models are frequently used to determine if drug compound candidates will be absorbed across the intestinal barrier, however, these in vitro studies are not always predictive. It has been shown that culture substrate chemistry influences cell phenotype and it is hypothesized that topography may also influence cellular function. The topography of the porcine intestinal basement membrane, which is similar to that of human, consists of finger-like projections called villi and well-like invaginations called crypts. In the crypts, undifferentiated cells begin to migrate toward the top of the villus, changing their cellular function as they move along the topography; indicating that cell culture substrate topography may be an important factor.

Chemical vapor deposition (CVD) provides an opportunity to recreate the intestinal basement membrane topography at the nano- and micro-scale for use in such drug transport studies as well as intestinal tissue engineering. CVD of silica films has been shown to replicate biological structures as small as 150 nm[ ]. These silica films are produced in a surface phase reaction between organic silanes and hydrogen peroxide at ambient temperatures, with no external excitation required. The gross dimensions of intestinal villi range in the order of 100-200ƒÝm, well within the range of CVD's ability to coat.

Removal of cells from the porcine intestinal basement membrane and preparation for CVD was accomplished through a multi-step fixation, maceration and dehydration procedure. Replication of the basement membrane was accomplished through chemical vapor deposition of a thin silica film. We have shown through SEM analysis that the topography of the porcine intestinal basement membrane was maintained, exhibiting visible crypt and villus structures. Ongoing work is being done to increase the mechanical properties of the replica by optimizing the formation of the silica matrix, verified through Fourier transform infrared (FTIR) spectroscopy.

1 Cook, G et al, Angewandte Chemie International Edition, 2003. 42(5): p.557-559.