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Collagen/Chitosan Hydrogel-Augmented Mesenchymal Stem Cell Therapy Attenuates Secondary Cellular Injury and Enhances Neuroregeneration Following Experimental Spinal Cord Injury

Carlos Martínez-López, PhD1,Elena Rodríguez-García, MD, PhD 2, Javier Fernández-Ortega, MD, PhD3 ORCID 

1Department of Neuroscience, Institute of Biomedical Research of Barcelona (IIBB), University
of Barcelona, Barcelona, Spain.
2Department of Regenerative Medicine and Tissue Engineering, Faculty of Medicine,
Autonomous University of Madrid, Madrid, Spain.
3Department of Neuroscience, Institute of Biomedical Research of Barcelona (IIBB), University of Barcelona, Barcelona, Spain.

DOI: 10.18081/2378-5225/15.54  
Cited by 0

 Article history: Received 09 March 2026 · Revised 27 March 2026 · Accepted 19 April 2026 · Published 05 May 2026

© 2026 Ortega, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0). 

CC BY 4.0                                                                                                   

Abstract

Background: Traumatic spinal cord injury (SCI) is a devastating neurological disorder characterized by irreversible neuronal loss, axonal degeneration, neuroinflammation, oxidative stress, and glial scar formation, all of which collectively limit functional recovery. Although mesenchymal stem cell (MSC)-based therapies have demonstrated regenerative potential in preclinical studies, poor cell survival and limited retention at the injury site remain major obstacles. Biomaterial-assisted cellular delivery has emerged as a promising strategy to enhance stem cell engraftment and improve neurological repair.

Objective: This study investigated the therapeutic efficacy of a collagen/chitosan hydrogel loaded with bone marrow-derived mesenchymal stem cells for promoting functional recovery and tissue regeneration following experimental spinal cord injury in rats.

Methods: Forty adult male Sprague-Dawley rats were randomly allocated into four experimental groups (n = 10/group): Sham, SCI control, Hydrogel, and Hydrogel + MSCs. A standardized thoracic spinal cord contusion injury was induced using the NYU weight-drop model. Animals received either no treatment, injectable collagen/chitosan hydrogel alone, or hydrogel containing cultured bone marrow-derived MSCs. Functional recovery was evaluated using the Basso-Beattie-Bresnahan (BBB) locomotor scale over eight weeks. Histopathological examination, immunohistochemistry, oxidative stress biomarkers, and inflammatory cytokines were analyzed to assess tissue regeneration and biological responses.

Results: Biomaterial-assisted MSC transplantation significantly improved locomotor recovery compared with untreated SCI animals. Histological analyses demonstrated marked preservation of spinal cord architecture, reduced lesion cavity formation, enhanced neuronal survival, improved myelin preservation, and increased axonal continuity. Immunohistochemical evaluation revealed increased NeuN, NF-200, and MBP expression together with decreased GFAP, Iba-1, and caspase-3 immunoreactivity. Furthermore, treatment significantly reduced malondialdehyde, tumor necrosis factor-α, interleukin-1β, and interleukin-6 levels while restoring endogenous antioxidant activity and increasing interleukin-10 expression.

Conclusion: Collagen/chitosan hydrogel-assisted mesenchymal stem cell transplantation effectively attenuated secondary spinal cord injury by suppressing inflammation, oxidative stress, apoptosis, and glial activation while promoting neuronal preservation, remyelination, and axonal regeneration. These findings support biomaterial-assisted stem cell therapy as a promising regenerative strategy for spinal cord repair and provide a foundation for future translational studies and clinical applications.

Keywords: Spinal cord injury; Mesenchymal stem cells; Biomaterials; Collagen hydrogel; Chitosan; Tissue engineering.

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BM-Publisher · Pathophysiology of Cell Injury Journal (PCIJ) · E-ISSN 2378-5225 · DOI Prefix 10.18081/pcij/2378-5225

Pathophysiology of Cell Injury Journal (PCIJ)
E-ISSN 2378-5225 · Biannual
BM-Publisher (London, UK)
Open Access

Vol 15, Issue 1 (May 2026), pp. 54–75

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Chaiyaporn A, Srisawat N, Lertsinudom K. Biomarkers of Neuronal Cell Injury in Acute Brain Insults: Correlation with Clinical Outcomes in ICU Patients. Pathophysiology of Cell Injury Journal (PCIJ). 2026;15(1):37–53. doi: 10.18081/2378-5225/15.37.

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