Dexamethasone-loaded platelet-inspired nanoparticles improve intracortical microelectrode recording performance

Longshun Li, Aniya Hartzler, Dhariyat M. Menendez-Lustri, Jichu Zhang, Alex Chen, Danny V. Lam, Baylee Traylor, Emma Quill, David E. Nethery, George F. Hoeferlin, Christa L. Pawlowski, Michael A. Bruckman, Anirban Sen Gupta, Jeffrey R. Capadona and Andrew J. Shoffstall ()
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Longshun Li: Case Western Reserve University
Aniya Hartzler: Case Western Reserve University
Dhariyat M. Menendez-Lustri: Case Western Reserve University
Jichu Zhang: Case Western Reserve University
Alex Chen: Case Western Reserve University
Danny V. Lam: Case Western Reserve University
Baylee Traylor: Haima Therapeutics LLC
Emma Quill: Haima Therapeutics LLC
David E. Nethery: Case Western Reserve University
George F. Hoeferlin: Case Western Reserve University
Christa L. Pawlowski: Haima Therapeutics LLC
Michael A. Bruckman: Haima Therapeutics LLC
Anirban Sen Gupta: Case Western Reserve University
Jeffrey R. Capadona: Case Western Reserve University
Andrew J. Shoffstall: Case Western Reserve University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Long-term robust intracortical microelectrode (IME) neural recording quality is negatively affected by the neuroinflammatory response following microelectrode insertion. This adversely impacts brain-machine interface (BMI) performance for patients with neurological disorders or amputations. Recent studies suggest that the leakage of blood-brain barrier (BBB) and microhemorrhage caused by IME insertions contribute to increased neuroinflammation and reduced neural recording performance. Here, we evaluated dexamethasone sodium phosphate-loaded platelet-inspired nanoparticles (DEXSPPIN) to simultaneously augment local hemostasis and serve as an implant-site targeted drug-delivery vehicle. Weekly systemic treatment or control therapy was provided to rats for 8 weeks following IME implantation, while evaluating extracellular single-unit recording performance. End-point immunohistochemistry was performed to further assess the local tissue response to the IMEs. Treatment with DEXSPPIN significantly increased the recording capabilities of IMEs compared to controls over the 8-week observation period. Immunohistochemical analyses of neuron density, activated microglia/macrophage density, astrocyte density, and BBB permeability suggested that the improved neural recording performance may be attributed to reduced neuron degeneration and neuroinflammation. Overall, we found that DEXSPPIN treatment promoted an anti-inflammatory environment that improved neuronal density and enhanced IME recording performance.

Date: 2025
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DOI: 10.1038/s41467-025-63583-z

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