pcij-2641-1787412857 20260822153417 PCIJ bmpublisher@bmpublisher.net Pathophysiology of Cell Injury Journal Pathophysiology of Cell Injury Journal 2378-5225 15 1 2026 5 5 Carlos Martínez-López Elena Rodríguez-García Javier Fernández-Ortega 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 application. Keywords: Spinal cord injury; Mesenchymal stem cells; Biomaterials; Collagen hydrogel; Chitosan; Tissue engineering. 2026 5 5 10.18081/2378-5225/15.54 https://pcij.net/archives/2641