Development and Characterization of an In-House Custom Bioreactor for the Cultivation of a Tissue Engineered Blood-Brain Barrier

Author

Amin Hadi Mirzaaghaeian, California Polytechnic State University, San Luis ObispoFollow

DOI: https://doi.org/10.15368/theses.2012.150
Available at: https://digitalcommons.calpoly.edu/theses/833

Date of Award

7-2012

Degree Name

MS in Biomedical Engineering

Department/Program

Biomedical and General Engineering

Advisor

Kristen Cardinal

Abstract

The development of treatments for neurological disorders such as Alzheimer’s and Parkinson’s disease begins by understanding what these diseases affect and the consequences of further manifestation. One particular region where these diseases can produce substantial problems is the blood-brain barrier (BBB). The BBB is the selective diffusion barrier between the circulating blood and the brain. The barrier’s main function is to maintain CNS homeostasis and protect the brain from the extracellular environment. The progression of BBB research has advanced to the point where many have modeled the BBB in vitro with aims of further characterizing and testing the barrier. Particularly, the pharmaceutical industry has gained interest in this field of research to improve drug development and obtain novel treatments for patients so the need for an improved model of the BBB is pertinent in their discovery. In the Cal Poly Tissue Engineering lab, an in vitro tissue engineered BBB system has previously been obtained and characterized for the initial investigation of the barrier and its components. However, certain limitations existed with use of the commercial system. Therefore, the focus of this thesis was to improve upon the capabilities and limitations of this commercialized system to allow further expansion of BBB research. The work performed was based on three aims: first to design and develop an in-house bioreactor system that could be used to cultivate the BBB; second, to characterize flow and functional capabilities of the bioreactor; third, to develop protocols for the overall use of the bioreactor, to ultimately allow co-cultures of BAEC and C6 glioma cells, and further the progression toward creating an in vitro model of the BBB.

The work of this thesis demonstrates development of an in-house custom bioreactor system that can successfully culture cells. Results showed that the system was reusable, could be sterilized and monitored, was easily used by students trained in the laboratory, and allowed non-destructive scaffold extraction. This thesis also discusses the next set of experiments that will lead to an in vitro model of the BBB.