Chitosan-Mediated Metformin Delivery Promotes Dose-Dependent Functional Recovery in a Rat Spinal Cord Injury Model

نویسندگان

1 Department of Pathobiology, SR.C., Islamic Azad University, Tehran, Iran.

2 Department of Veterinary Clinical Sciences, SR.C., Islamic Azad University, Tehran, Iran.

3 Department of Veterinary Clinical Sciences, SR.C., Islamic Azad University, Tehran, Iran.

4 Department of Veterinary Clinical Sciences, SR.C., Islamic Azad University, Tehran, Iran.

doi
10.30500/ivsa.2025.528959.1451
چکیده

Spinal cord injury (SCI) is a severe condition characterized by primary mechanical damage followed by secondary injury mechanisms, which worsen cellular dysfunction and death. Current treatment strategies remain insufficient in mitigating the full consequences of SCI. Metformin (Met) has demonstrated neuroprotective effects in the central nervous system (CNS), raising interest in its therapeutic potential for SCI. However, whether a chitosan (CH) hydrogel loaded with Met can enhance functional recovery after SCI remains unclear. Wistar rats were divided into five groups: a sham group, an SCI group (negative control, NC), and three groups receiving CH hydrogel containing 10, 50, and 100 mg/kg of Met. Behavioral assessments, including locomotor scoring and sensorimotor function tests, demonstrated that sustained delivery of the metformin-chitosan hydrogel significantly enhanced functional recovery in spinal cord-injured rats compared to untreated controls. Quantitative analysis revealed notable improvements in hindlimb coordination, weight-bearing capacity, and reflex responses, suggesting partial restoration of neural circuitry. Furthermore, the CH/Met hydrogel group exhibited accelerated recovery kinetics, with earlier onset of motor improvements relative to standard treatments. These findings collectively supported the therapeutic efficacy of CH/Met hydrogel in mitigating SCI-related deficits, potentially through its combined neuroprotective and regenerative mechanisms.