Rebecca L. Carrier
Daniel D. Burkey, Shashi Krishna Murthy
Date of Award
Master of Science
Department or Academic Unit
College of Engineering. Department of Chemical Engineering.
chemical engineering, biomedical engineering, chemical vapor deposition (CVD)
Intestines, Membranes (Biology), Chemical vapor deposition
Biochemistry | Molecular, cellular, and tissue engineering
In 2010, oral drug delivery was a $49 billion industry. The major portal for the uptake of medicines delivered orally is the small intestine. One of the greatest features of the small intestine is the large surface area, created by an intricate structure of finger-like projections called villi and well-like invaginations called crypts. To help predict bioavailability of rapidly developed candidate drug compounds, cell culture models are frequently used. However, these tests are often inaccurate. It is hypothesized that the lack of cell culture substrate biochemistry and topography are major factors in the difference in cell function between in vivo and in vitro transport studies.
Chemical vapor deposition (CVD) provides the capability of recreating the intestinal basement membrane topography; it has been used to deposit silica coatings which have been shown to exactly replicate complex three-dimensional biological structures as small as 150 nm. Also, plasma enhanced CVD (PECVD) has been used to deposit a biocompatible, biodegradable polymer, poly(2-hydroxyethyl methacrylate) (pHEMA), with tunable amounts of cross-linking. However, literature reports that photoinitiated CVD (piCVD) produces a more chemically pure pHEMA film than PECVD.
It was found that the basement membrane of a porcine small intestine could be uncovered through an aldehyde-based fixation and maceration. CVD silica was then utilized to deposit a thin conformal layer upon the basement membrane. The silica was seen to replicate the villus and crypt structure on the order of 100 um and pores, on the surface of the villi, on the order of 5 um. However, it was found that sphere-like nanostructures masked the fibrous makeup of the basement membrane at the 100 nm scale.
piCVD was utilized to deposit pHEMA films of varying degrees of cross-linking. It was found that the degree of cross-linking affected the degree to which films swelled and degraded, with the cross-linked films having the least amount of water uptake and maintaining film thickness over a 21 day incubation. It was also found that after 3 days the cross-linked films exhibited relative cell attachment equal to that of polystyrene, the industry norm, whereas the non cross-linked films showed 50% attachment.
Brian Jarrett McMahon
McMahon, Brian Jarrett, "Multi-scale replication of small intestine basement membrane via chemical vapor deposition" (2010). Chemical Engineering Master's Theses. Paper 11. http://hdl.handle.net/2047/d20001043
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