This semester I worked in the Musculoskeletal Soft Tissue Laboratory to explore the potential drug therapies for post-traumatic joint contracture (PTJC), or arthrofibrosis, in the elbow following a traumatic joint injury. To simulate the potential effects of these drugs in the elbow post-injury, this study utilized an in-vitro model using collagen gels and NIH-3T3 cells to mimick the contraction of capsule tissue in the elbow and the cells thought to contribute to disease progression in the capsule, namely fibroblasts and myofibroblasts. The first part of the study tested the effects of two drugs, losartan and simvastatin, on decreasing contraction. The standard testing procedure required that the gels be seeded with cells, then administered the appropriate drug concentration and mixture, and then observed for a period of six days. Once we narrowed down the drug formulations to a few possible candidates, we considered the issues related to timing of treatment and pharmacokinetics of these drugs if administered into the human elbow; more specifically, we wanted to understand how factors like drug clearance, or the treatment of PTJC after its onset, would affect the drug’s effectiveness. To this end, the second part of the study looked at how exposure time of the drug to the cells affected the drug’s function; more specifically, the impact of both time delay and a shorter exposure period on the performance of the drugs were explored. It quickly became apparent through these studies that simvastatin could halt contraction, but did nothing to reverse it. The third and final part of the study tested the ability of the hormone relaxing on decreasing contraction. By the end of the semester, we determined that,within the construct of our experimental set-up and parameters, simvastatin was the only promising candidate for treatment of PTJC.
Mechanical Engineering and Material Sciences Independent Study
Date of Submission
Shah, Ishani D.; David, Michael; and Lake, Spencer, "Exploration of Drug Therapies for Post-Traumatic Elbow Joint Contracture" (2020). Mechanical Engineering and Materials Science Independent Study. 116.