Design of In-Vitro Primate Model for Optimization of Intrathecal Drug Delivery
Additional Funding Sources
The project described was supported by the National Science Foundation under Award No. 1826715. Additional funding was provided by the Engineering Grand Challenge Scholars Program at the University of Idaho.
Abstract
Intrathecal drug delivery shows promise in treating central nervous system (CNS) disease because it bypasses limitations posed by the blood-brain-barrier and reduces systemic shock. Non-human primates (NHPs) are important animal models for intrathecal therapy development; however, primate studies are expensive and practically difficult. Additionally, little is known about the differences in cerebrospinal fluid (CSF) dynamics between NHPs and humans. In the present study, we present work towards a 3D-printed in vitro platform of the NHP cerebrospinal fluid system for development of intrathecal drug delivery to the CNS. To obtain CSF geometry, T2-weighted MRI imaging of a cynomolgus monkey CNS was collected and segmented. Optimization of the segmented geometry and the addition of 31 nerve root pairs based on a previously published human model [1] was completed. Finally, supporting geometry including assembly flanges and access ports were also added. Future work will focus on 3D-printing the finished geometry and construction of a complete benchtop system. Characterization of the fluid dynamics in this model will be studied via phase contrast MRI and fluorescent time-lapse imaging. This will allow comparison to a similar in vitro human model already completed by our group and provide boundary conditions for computational studies [2].
[1] L. R. Sass, Fluids Barriers CNS, vol. 14, p. 36, Dec 19 2017.[2] M. Khani, et al., PLoS One, vol. 14, p. e0212239, 2019
Design of In-Vitro Primate Model for Optimization of Intrathecal Drug Delivery
Intrathecal drug delivery shows promise in treating central nervous system (CNS) disease because it bypasses limitations posed by the blood-brain-barrier and reduces systemic shock. Non-human primates (NHPs) are important animal models for intrathecal therapy development; however, primate studies are expensive and practically difficult. Additionally, little is known about the differences in cerebrospinal fluid (CSF) dynamics between NHPs and humans. In the present study, we present work towards a 3D-printed in vitro platform of the NHP cerebrospinal fluid system for development of intrathecal drug delivery to the CNS. To obtain CSF geometry, T2-weighted MRI imaging of a cynomolgus monkey CNS was collected and segmented. Optimization of the segmented geometry and the addition of 31 nerve root pairs based on a previously published human model [1] was completed. Finally, supporting geometry including assembly flanges and access ports were also added. Future work will focus on 3D-printing the finished geometry and construction of a complete benchtop system. Characterization of the fluid dynamics in this model will be studied via phase contrast MRI and fluorescent time-lapse imaging. This will allow comparison to a similar in vitro human model already completed by our group and provide boundary conditions for computational studies [2].
[1] L. R. Sass, Fluids Barriers CNS, vol. 14, p. 36, Dec 19 2017.[2] M. Khani, et al., PLoS One, vol. 14, p. e0212239, 2019
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