Neuritogenic glycosaminoglycan hydrogels promote functional recovery after severe traumatic brain injury.

Autor:	Gonsalves N; Regenerative Bioscience Center, University of Georgia, Athens, GA, United States of America.; Division of Neuroscience, Biomedical and Translational Sciences Institute, University of Georgia, Athens, GA, United States of America., Sun MK; Regenerative Bioscience Center, University of Georgia, Athens, GA, United States of America.; Division of Neuroscience, Biomedical and Translational Sciences Institute, University of Georgia, Athens, GA, United States of America., Chopra P; Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States of America., Latchoumane CF; Regenerative Bioscience Center, University of Georgia, Athens, GA, United States of America.; Edgar L. Rhodes Center for Animal and Dairy Science, College of Agriculture and Environmental Sciences, University of Georgia, Athens, GA, United States of America., Bajwa S; Regenerative Bioscience Center, University of Georgia, Athens, GA, United States of America., Tang R; Regenerative Bioscience Center, University of Georgia, Athens, GA, United States of America.; Edgar L. Rhodes Center for Animal and Dairy Science, College of Agriculture and Environmental Sciences, University of Georgia, Athens, GA, United States of America., Patel B; Regenerative Bioscience Center, University of Georgia, Athens, GA, United States of America., Boons GJ; Complex Carbohydrate Research Center, University of Georgia, Athens, GA, United States of America.; Department of Chemistry, University of Georgia, Athens, GA, United States of America.; Department of Chemical Biology and Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, and Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands., Karumbaiah L; Regenerative Bioscience Center, University of Georgia, Athens, GA, United States of America.; Division of Neuroscience, Biomedical and Translational Sciences Institute, University of Georgia, Athens, GA, United States of America.; Edgar L. Rhodes Center for Animal and Dairy Science, College of Agriculture and Environmental Sciences, University of Georgia, Athens, GA, United States of America.
Jazyk:	angličtina
Zdroj:	Journal of neural engineering [J Neural Eng] 2024 Jun 27; Vol. 21 (3). Date of Electronic Publication: 2024 Jun 27.
DOI:	10.1088/1741-2552/ad5108
Abstrakt:	Objective. Severe traumatic brain injury (sTBI) induced neuronal loss and brain atrophy contribute significantly to long-term disabilities. Brain extracellular matrix (ECM) associated chondroitin sulfate (CS) glycosaminoglycans promote neural stem cell (NSC) maintenance, and CS hydrogel implants have demonstrated the ability to enhance neuroprotection, in preclinical sTBI studies. However, the ability of neuritogenic chimeric peptide (CP) functionalized CS hydrogels in promoting functional recovery, after controlled cortical impact (CCI) and suction ablation (SA) induced sTBI, has not been previously demonstrated. We hypothesized that neuritogenic (CS)CP hydrogels will promote neuritogenesis of human NSCs, and accelerate brain tissue repair and functional recovery in sTBI rats. Approach. We synthesized chondroitin 4- O sulfate (CS-A)CP, and 4,6- O -sulfate (CS-E)CP hydrogels, using strain promoted azide-alkyne cycloaddition (SPAAC), to promote cell adhesion and neuritogenesis of human NSCs, in vitro ; and assessed the ability of (CS-A)CP hydrogels in promoting tissue and functional repair, in a novel CCI-SA sTBI model, in vivo. Main results. Results indicated that (CS-E)CP hydrogels significantly enhanced human NSC aggregation and migration via focal adhesion kinase complexes, when compared to NSCs in (CS-A)CP hydrogels, in vitro . In contrast, NSCs encapsulated in (CS-A)CP hydrogels differentiated into neurons bearing longer neurites and showed greater spontaneous activity, when compared to those in (CS-E)CP hydrogels. The intracavitary implantation of (CS-A)CP hydrogels, acutely after CCI-SA-sTBI, prevented neuronal and axonal loss, as determined by immunohistochemical analyses. (CS-A)CP hydrogel implanted animals also demonstrated the significantly accelerated recovery of 'reach-to-grasp' function when compared to sTBI controls, over a period of 5-weeks. Significance. These findings demonstrate the neuritogenic and neuroprotective attributes of (CS)CP 'click' hydrogels, and open new avenues for the development of multifunctional glycomaterials that are functionalized with biorthogonal handles for sTBI repair. (Creative Commons Attribution license.)
Databáze:	MEDLINE
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