UCSD Bioreactor for Tissue Regeneration

Background

Stem cells are a type of human cell that has the ability to differentiate into a variety of different cell types based on environmental stimuli in the human body. They are used throughout natural developmental processes in addition to healing mechanisms. Mesenchymal stem cells are a well studied cell type that possesses anti-inflammatory and immunosuppressive characteristics (Mesenchymal Stem Cells). These cells are widely studied for the treatment of chronic degenerative diseases and are used on the forefront of the newly emerged field of regenerative medicine. To provide an example of the commercial use of stem cells, ex vivo expanded hematopoietic cord blood stem cells are currently approved by the United States Food and Drug Administration for the treatment of over 80 diseases (Cord For Life). Other specific tissue sources for stem cells include adipose fat, umbilical cord Wharton jelly, and placental derived stem cells. Considering the widespread potential applications for stem cells, additional research is needed to understand their proliferation and differentiation patterns.

Project Overview

For the MAE 156A/B senior design project, students are tasked with the assignment of commercializing a design solution for an industry project. The “Cell Growth Bioreactor for Tissue Regeneration” was presented to our group by Peter Chen of the Biosciences Institute. The goal of this project is to create a chamber where specific mesenchymal stem cell growth conditions can be modified for research purposes. The sponsor is interested in electrical field stimulation, magnetic field stimulation, ability to modulate pressure, and finally the ability to modulate shear stress within the culture chamber. Within the context of our project, we have decided to focus on electrical stimulation, magnetic stimulation, and modification of static pressure. If project resources and time allocations permit, the project scope will be expanded to include dynamic pressures and application of shear stresses to cells within the chamber.

Objective

Our Sponsor, Peter Chen, provided specific information about target field requirements for the electric and magnetic field strength for the project. The chamber should be designed such that a 70hz 15 Gauss magnetic field may be applied to the cells. In terms of electrical stimulation, the sponsor indicated that he would like to see a target field value of 20V/cm, with 5V/cm would also be an acceptable lower target value if power supply constraints should be an issue (Leppik). With respect to the pressure ranges applied, based on a review of the literature around compressive pressures applied to cell culture, the static pressure value would be less than 12,000 Pa or 1.74 psi (Guo). The culture chamber would need to be designed such that the volume of the chamber can be adjusted to change the pressure applied to the cells within the chamber. It is also a design requirement that concurrent imaging is possible while the magnetic and electric fields are applied. The cell culture should occur within the 34mm average objective lens distance for a microphone, so that a bottom-viewing microscope can be utilized. Finally, an important design consideration is the ability to return to a factory state of cleanliness. Within the biotechnology industry, autoclave methodologies are used to clean labware. We need to design our system such that all surfaces in contact with the cells can withstand autoclave temperatures of approximately 121C.

References

Guo, Ting, et al. “Effect of Dynamic Culture and Periodic Compression on Human Mesenchymal Stem Cell Proliferation and Chondrogenesis.” Annals of Biomedical Engineering, vol. 44, no. 7, 2015, pp. 2103–2113., doi:10.1007/s10439-015-1510-5.

Leppik, Liudmila, et al. “Construction and Use of an Electrical Stimulation Chamber for Enhancing Osteogenic Differentiation in Mesenchymal Stem/Stromal Cells In Vitro.” Journal of Visualized Experiments, no. 143, 2019, doi:10.3791/59127.