ABSTRACT
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 after sTBI has not been investigated. We report that neurotrophic factor functionalized acellular eCS matrices implanted into the rat M1 region acutely post-sTBI, significantly enhanced cellular repair and gross motor function recovery when compared to controls, 20 weeks post-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 post-sTBI can support complex cellular, vascular, and neuronal circuit repair, chronically after sTBI.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
1. Minor mismatch for figure citation in text: Result section: p5: Fig 7A-C and E -> Sup Fig 6A-C and E p5: Sup Fig 8E -> Sup Fig 7E p6: Fig 6D -> Fig 5D p7: Fig2 -> Fig4 2. Missing Scale bars and Labels in Fig 1C and E 3. Figure Miss Label: Fig 5C-D 4. Missing Figure caption (Fig 5E-F) 5. Missing Figure Label: Sup Fig 11F 6. Minor typos and Grammar fixes 7. Authors middle initial and ORCID added 8. Mislabeling Methods: T2WI
