The Development of an In-Vitro System for the Study of Osteoarthritis in a Mouse Model
Nehme, Christopher.
2017
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Abstract: Osteoarthritis (OA) is a painful and debilitating disease of the
human joints. Sufferers of OA face a lifelong struggle with the chronic disease. Current
treatment options are directed at pain and inflammation management, occasionally
culminating in total joint replacements for qualifying patients. To date, no comprehensive
treatments have been developed, partially attributed to limi... read moretations in current OA research
models. With the incidence of OA constantly on the rise, in part due to our aging
population and increasing life spans, the necessity of comprehensive treatment options is
becoming inevitable. A novel model for studying OA in a mouse model was developed. A first
generation system capable of actuating and culturing amputated murine stifle joints was
designed, fabricated and tested. The system comprises of: a mechanical device that
maintains a stifle joint in a culture medium reservoir and actuates the joint through a
controlled flexion-extension profile; and a microcontroller board used to run an open-loop
controller supporting the device's function. The system was used to investigate the effects
of actuation and culture medium glucose concentration on the articular cartilage of stifle
joints harvested from eight-week-old NFκB/Balb C mice. Results suggest that a high
concentration of glucose (9.0 mg/ml) in Dulbecco's Modified Eagle's Medium (DMEM) used to
culture dynamically actuated joints promotes a higher degree of joint damage as measured by
quantification of Safranin-O staining loss, as opposed to moderate (4.5 mg/ml) and low (1.0
mg/ml) glucose concentrations. A second-generation system was then developed, addressing
limitations identified in the first-generation system related to repeatability, reliability
and usability. The design process focused on developing a pair of robust coupled four bar
linkage systems with the ability to repeatedly actuate the joint through a well-defined and
repeatable flexion extension cycle. A novel joint clamping and mounting system was also
developed to minimize user uncertainty associated with experimental set ups. The device's
function is supported by a closed-loop speed control system combining proportional-integral
(PI) action with an iterative feed forward controller. The superior controllability of this
system allowed investigation into the effects of actuation cycle rate and relative
activity-rest durations on joint health. Results demonstrate that the system is capable of
causing a range of damage as measured by Safranin-O staining loss on joint samples by
varying activity cycle durations. Finally, substantial work was directed towards extending
the functionality of the second-generation system to implement active loading control,
effectively allowing the device to control the loads at a mounted stifle joint as function
of the cycle position. A second PI control system was developed to control load by sensing
bending torque in a system link. Extensive experimental and analytical modeling was
performed to develop a working control system. Several limitations of the controllability
were determined due to the system geometry and assumptions made during the design process.
Nevertheless, it was successfully demonstrated that with proper loading profile
considerations, accurate control could be achieved, opening the door for a plethora of
future research.
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Mechanical Engineering.
Advisor: William Messner.
Committee: Li Zeng, Robert White, and Alan Grodzinsky.
Keywords: Mechanical engineering, Biomedical engineering, and Biology.read less - ID:
- 3r075589w
- Component ID:
- tufts:22434
- To Cite:
- DCA Citation Guide EndNote
