(165i) In Vitro Human Spine Model Manufacturing and Applications to Intrathecal Drug Delivery

Intrathecal drug (IT) delivery can efficiently target regions in the central nervous system without hindrance of the blood brain barrier. This delivery mode is especially promising for novel therapeutics such as enzyme replacement, gene, or antisense oligonucleotide (ASO) therapies for the treatment of neurodegenerative diseases including Alzheimer’s, Huntington’s disease, and stroke. Due to the high risk to patients and technical limitations of acquiring high speed CSF flow and bio-distribution data with existing imaging modalities (e.g., MRI, PET), in human in vivo study cannot be performed. Novel, fast, relatively cheap, and subject specific in-vitro method to study the drug bio-dispersion mechanism and optimize the intrathecal drug therapies for individual patients is in great need. Here, we present model design and additive manufacturing process for producing a subject specific spine which replicated the interaction of the human spine with the cerebrospinal fluid (CSF). The model was manufactured using the 3-dimensional (3D) printing technology or additive manufacturing. The printing was done with the used of imaging data set which helps in acquiring the geometry through which 3D mesh was created with the use of computer-aided design (CAD). The developed phantom is watertight, anatomically accurate, physiological functional, deformable - which allows it to produce pulsation as experienced in the real human spine, and transparent – which allows it the be suitable for intrathecal (IT) tracer dispersion experiment as it is very easy to track, in real time, the spread of the tracer in the phantom. The manufactured phantom was used for IT tracer dispersion study using different parameters such as infusion rate, and frequency of pulsation.