Patch Delivery of Brain-Derived Neurotrophic Factor for the Treatment of Sensorineural Hearing Loss
BME 401: Numerical Simulations in Biomedical Engineering
Jan-Apr 2023
Objective
For this class's semester-long final project, students were asked to form a team, identify a biomedical problem, design a solution, and model its function computationally.
My Role
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Created the final geometry using a line and three quadratic beziers
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Designed and executed the study using COMSOL Multiphysics
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Contributed to the research of various study design factors in relevant literature and similar studies as well as the interpretation of the study results and future implications
Background
Sensorineural hearing loss accounts for the majority of hearing loss cases in the United States and is becoming increasingly more common. It progresses from the damage of hair cells in the inner ear which function to stimulate nerve impulses for the brain to interpret sound waves. These hair cells continue to degrade over time and are not regenerative. Current treatments include hearing aids or cochlear implants, however, such devices only serve to mitigate a progressively worsening condition rather than treat and improve it.
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My high school AP Research Capstone paper addressed this issue as well. In continuation of my conclusions from that research, targeted delivery of brain-derived neurotrophic factor (BDNF) poses a potential solution for treating sensorineural hearing loss.
Approach
We suggested the implantation of a drug-delivery patch containing BDNF in the inner wall of the Scala vestibuli. Using COMSOL Multiphysics, a 2D geometry was created depicting a simplified cross section of the Scala tympani, and a study was designed to simulate the diffusion of BDNF from the theoretical location of the patch to the location of the hair cells.
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Properties of water were used to model the endolymph fluid, and natural endolymph movement was neglected in this study design in order to meet Reynolds incompressibility.
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A Physics-controlled mesh with an extra fine element size was applied to the geometry, an initial patch concentration of 20 mol/m3 was set, and the diffusion was modeled over the course of four weeks.
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Goals
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Visualize the diffusion of BDNF toward the base of the semicircular canal where the hair cells are supposedly located.
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Visualize this diffusion at each time step across the radius of the geometry.
Outcomes
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The majority of BDNF remains concentrated closer to the patch than the hair cells.
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Literature shows only 2 mol/m3 of BDNF is necessary for effective treatment of hair cells, and this study design results in this amount of BDNF successfully reaching the base of the canal by the end of the four-week period.​
Surface: Concentration (mol/m3)
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Time = 0h
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Time = 168h
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Time = 336h
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Time = 672h
Line Graph: (mol/m3)
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Arc Length (m)
Future Study Considerations
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The cross-sectional geometry in this study depicts the largest radius of the Scala tympani, which narrows throughout. In future studies, the initial patch concentration can be adjusted for placement at smaller cross-sectional radii of the Scala tympani and the diffusion in a narrowing 3D semicircular tube can be modeled.
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Over longer periods of time as a patient is not stationary, endolymph movement may not be negligible, and its effects should be accounted for in future studies of BDNF diffusion through the fluid.
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The weight of the patch in this study was calculated to be 0.02g. For various initial patch concentrations, the weight of the patch may influence the patient’s balance and should be considered in future studies and applications.
My Final Thoughts
I further recommend that the development of future hearing loss solutions focus on addressing the continual degradation of hair cells by slowing or stopping this process or even regenerating already damaged hair cells.​