A Neurocompliant Ionic Conductive Hydrogel Orchestrates Glial and Vascular Remodeling to Mitigate Traumatic Brain Injury
- 1University of California, Riverside
Abstract
Developing conductive scaffolds for neural regeneration is often hindered by the cytotoxicity and mechanical mismatch inherent to conventional electronic fillers. Here, we report an ultrasoft ionically conductive hydrogel engineered by grafting choline-based bioionic liquids (BIL) onto fish gelatin (FiBGel). Systematic optimization yields brain-mimetic conductivity (0.25-0.68 S/m), elastic moduli (0.6-0.9 kPa), and physiological water content (72-81%). In 3D culture, the matrix drives spontaneous neurogenesis, achieving ~90% MAP2+ neurons with robust calcium signaling, while concurrently supporting endothelial network formation. We report the first intracerebral administration of a BIL hydrogel, demonstrating remarkable biocompatibility and immunomodulation. In a traumatic brain injury model, a single FiBGel dose halves reactive astrogliosis, enhances cortical revascularization, and limits lesion cavity expansion. Leveraging an FDA-recognized micronutrient, FiBGel offers a translatable strategy that integrates neuromechanics, conductivity, immune modulation, and vascular support within one injectable scaffold for minimally invasive treatment of brain injuries.
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BibTeX
@misc{okoro2026neurocompliant,
title = {{A Neurocompliant Ionic Conductive Hydrogel Orchestrates Glial and Vascular Remodeling to Mitigate Traumatic Brain Injury}},
author = {P. D. Okoro and R. Jaberi and S. Blackburn and D. Patel and N. Halasah and J. Mapa and M. Shih and R. Botzbach and J. Tan and V. I. Vullev and H. Liu and V. Santhakumar and I. Noshadi},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.29.762869},
url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762869v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - A Neurocompliant Ionic Conductive Hydrogel Orchestrates Glial and Vascular Remodeling to Mitigate Traumatic Brain Injury
AU - P. D. Okoro
AU - R. Jaberi
AU - S. Blackburn
AU - D. Patel
AU - N. Halasah
AU - J. Mapa
AU - M. Shih
AU - R. Botzbach
AU - J. Tan
AU - V. I. Vullev
AU - H. Liu
AU - V. Santhakumar
AU - I. Noshadi
PY - 2026
DA - 2026/10/29
PB - bioRxiv
DO - 10.64898/2026.10.29.762869
UR - https://www.biorxiv.org/content/10.64898/2026.10.29.762869v1
AB - Developing conductive scaffolds for neural regeneration is often hindered by the cytotoxicity and mechanical mismatch inherent to conventional electronic fillers. Here, we report an ultrasoft ionically conductive hydrogel engineered by grafting choline-based bioionic liquids (BIL) onto fish gelatin (FiBGel). Systematic optimization yields brain-mimetic conductivity (0.25-0.68 S/m), elastic moduli (0.6-0.9 kPa), and physiological water content (72-81%). In 3D culture, the matrix drives spontaneous neurogenesis, achieving ~90% MAP2+ neurons with robust calcium signaling, while concurrently supporting endothelial network formation. We report the first intracerebral administration of a BIL hydrogel, demonstrating remarkable biocompatibility and immunomodulation. In a traumatic brain injury model, a single FiBGel dose halves reactive astrogliosis, enhances cortical revascularization, and limits lesion cavity expansion. Leveraging an FDA-recognized micronutrient, FiBGel offers a translatable strategy that integrates neuromechanics, conductivity, immune modulation, and vascular support within one injectable scaffold for minimally invasive treatment of brain injuries.
ER -