Engineered glycomaterial implants orchestrate large-scale functional repair of brain tissue chronically after severe traumatic brain injury.

Journal Article (Journal Article)

Severe traumatic brain injury (sTBI) survivors experience permanent functional disabilities due to significant volume loss and the brain's poor capacity to regenerate. Chondroitin sulfate glycosaminoglycans (CS-GAGs) are key regulators of growth factor signaling and neural stem cell homeostasis in the brain. However, the efficacy of engineered CS (eCS) matrices in mediating structural and functional recovery chronically after sTBI has not been investigated. We report that neurotrophic factor functionalized acellular eCS matrices implanted into the rat M1 region acutely after sTBI significantly enhanced cellular repair and gross motor function recovery when compared to controls 20 weeks after sTBI. Animals subjected to M2 region injuries followed by eCS matrix implantations demonstrated the significant recovery of "reach-to-grasp" function. This was attributed to enhanced volumetric vascularization, activity-regulated cytoskeleton (Arc) protein expression, and perilesional sensorimotor connectivity. These findings indicate that eCS matrices implanted acutely after sTBI can support complex cellular, vascular, and neuronal circuit repair chronically after sTBI.

Full Text

Duke Authors

Cited Authors

  • Latchoumane, C-FV; Betancur, MI; Simchick, GA; Sun, MK; Forghani, R; Lenear, CE; Ahmed, A; Mohankumar, R; Balaji, N; Mason, HD; Archer-Hartmann, SA; Azadi, P; Holmes, PV; Zhao, Q; Bellamkonda, RV; Karumbaiah, L

Published Date

  • March 5, 2021

Published In

Volume / Issue

  • 7 / 10

Start / End Page

  • eabe0207 -

PubMed ID

  • 33674306

Pubmed Central ID

  • PMC7935369

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

International Standard Serial Number (ISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.abe0207

Language

  • eng