ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Biomechanics
In vitro design of intrathecal drug administration therapies
Provisionally accepted
Ayankola O Ayansiji1,2Caleb Gardner1Sebastien Dors3
Daniel Gehrke1
Francisco Moral-Pulido1Charles Nicholson4
Konstantin Slavin5
Andreas A Linninger1,5*- 1Department of Bioengineering, University of Illinois Chicago, Chicago, United States
- 2Department of Chemical Engineering, University of Illinois Chicago, Chicago, United States
- 3UIC Student Intern From EPF, Ecole D’Ingénieur, Paris, France
- 4New York University Department of Neuroscience and Physiology, New York, United States
- 5Department of Neurosurgery, University of Illinois Chicago, Chicago, United States
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Due to the scarcity of reliable in vivo data, the pharmacokinetics of intrathecally (IT) administered drugs remain inadequately quantified. Designing new therapies is further hindered by variability in experimental methods, inter-individual and inter-species differences, and poor reproducibility across animal and human studies. To address these limitations, we developed an anatomically accurate, subject-specific replica of the cerebrospinal fluid-filled spaces of the human central nervous system (CNS) using a multistep mold/casting process. The 3D-printed, transparent, deformable CNS phantom enables precise control of infusion and physiological parameters, allowing systematic generation of reliable and repeatable biodispersion data for lumbar IT infusion protocols. Pulsatile artificial cerebrospinal fluid (CSF) flow within the closed system was tuned to replicate subject-specific stroke volumes and flow rates observed in MRI. The model's optical clarity facilitated high-speed visualization and tracking of tracer dispersion, exceeding the temporal resolution of current neuroimaging techniques. Experimental series spanning physiologically relevant CSF and infusion conditions enabled quantification of the spatiotemporal distribution of IT-administered tracers. Inversion of the parabolic diffusion equation provided estimates of the coefficient of effective dispersion. A distributed pharmacokinetic model was used to evaluate the influence of chemical kinetics and mass transfer on tracer behavior. The proposed experimental apparatus for in vitro design of IT therapies offers a complementary or alternative approach to traditional trial-and-error animal studies.
Keywords: geometry-induced mixing, inversion of parabolic diffusion equation, Intrathecal drug delivery, oscillatory CSF flow, in vitro deformable spine model, drug infusion parameters, Pharmacokinetic modeling
Received: 19 Jul 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Ayansiji, Gardner, Dors, Gehrke, Moral-Pulido, Nicholson, Slavin and Linninger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Andreas A Linninger
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