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Neural Engineering

Neural Engineering - Poster Session C

Poster K5 - Impact of a Biomimetic Coating on the Brain Tissue Reaction to Microdialysis Implants

Friday, October 25, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Microdialysis probes are used in vivo to monitor the fluctuation of biochemicals in the brain which provide significant insights into the brain’s physiology and pathology to study TBI, spinal cord injury, Parkinson’s disease and more. However, insertion of probes into the brain activates a foreign body response that involves immune cell activation and neuron degeneration. The resulting reactive tissue responses and impermeable gliosis interrupt the functionality of microdialysis probes as they lose the ability to exchange molecules with their surroundings. Surface modifications utilizing anti-inflammatory drug coatings or bioactive molecule immobilization hold great potential to improve chronic performance. Coating neural device surfaces with L1, a cell adhesion glycoprotein, has been shown to improve biocompatibility by increasing neural attachment and neurite length and decreasing astrocyte attachment, resulting in better performance from neural recording electrodes. This study aims to improve the biocompatibility of dialysis implants with L1 surface coating for lowered immune response and more stable in vivo microdialysis biochemical sensing.

Materials and

Methods:  L1CAM was extracted from homogenized rat pup brain tissue using affinity column chromatography. Vertical concentric microdialysis probes were either purchased from a commercial vendor or constructed with a hollow fiber dialysis membrane. Two commonly used membrane materials, cellulose and polyethersulfone (PES) probes were compared. The probe membrane surfaces were functionalized to introduce a carboxyl group using sodium periodate for the cellulose surface and a laccase mediated reaction for the PES surface. Subsequent covalent attachment of the L1 protein was done through crosslinking with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) in combination with N-hydroxysuccinimide (NHS). Ethanolamine was used to cap the unreacted EDC/NHS ester after L1 linking. To examine the interplay between brain tissue and surface chemistry, probes with five chemical treatment conditions duplicated for the two materials were created and implanted into rat cortex. The chemical conditions were as follows: bare; EDC/NHS coated; EDC/NHS and L1 coated; EDC/NHS and ethanolamine coated; EDC/NHS, L1, and ethanolamine coated. The brains of the rats were harvested after 1 week. We studied neuron density (NeuN – neuronal nuclei and NF200- neurofilament), immune response (IBA-1 – microglia, GFAP – astrocyte, iNOS – M1 microglia, and ARG – M2 microglia), and tissue damage (IgG – blood brain barrier leakage and CAP3- apoptosis). Ongoing confocal fluorescence imaging and quantitative image analysis will reveal the cellular responses to each surface chemistry.

Results, Conclusions, and Discussions: The histology results show that IBA-1 intensity was greater for the bare probes compared to those coated with L1, suggesting that L1 reduced microglial activation. The probes with ethanolamine had greater IBA-1 intensity compared to those without. GFAP, marking astrocytes, had the lowest intensity for the L1 coating without ethanolamine. CAP3 intensity was higher for the probe with EDC/NHS and ethanolamine, indicating potentially pro-inflammatory effects of ethanolamine. Image and subsequent data analysis demonstrates that L1 can improve the biocompatibility of the microdialysis probe by reducing the immune reaction in the neural tissue. Ethanolamine treated conditions are associated with more microglia presence and more neuron apoptosis than groups without ethanolamine, possibly due to the high-density hydroxyl groups. Further analysis will provide more insights into the cellular effects of each surface chemistry. Another interesting finding was the presence of cell, mostly microglial, penetration into the porous PES membranes.

Acknowledgements (Optional):