Collagen‐Based Hydrogel Loaded With Microspheres Encapsulated With Placental Mesenchymal Stem Cells‐Derived Exosomes Synergistically Promote Recovery After Spinal Cord Injury in Rats

Traumatic spinal cord injury (TSCI) is a serious medical issue where there is a loss of sensorimotor function. Current interventions continue to lack the ability to successfully enhance these conditions; therefore, it is crucial to consider alternative effective strategies. Currently, we investigated the effects of collagen-based hydrogel (CbH) loaded with microspheres encapsulated with placental mesenchymal stem cells (PMSCs)-derived exosomes in the recovery of TSCI in rats. Sixty adult male Sprague-Dawley rats were randomly assigned into four groups (n = 15/group): TSCI (injury without treatment), CbH, Microsphere (exosomes encapsulated in microspheres), and CbH + Microsphere. At 48 h, 10 rats per group were sacrificed for immunohistochemical (caspase-3), molecular (cytokines), and biochemical (oxidative stress markers) analyses; the remaining five rats per group were used for stereological evaluations at day 14. Furthermore, behavioral assessment was performed pre-injury and on days 1, 3, 7, and 14 post-injuries. Results showed that the CbH + Microsphere group exhibited significantly reduced lesion volume and apoptosis, improved neuron preservation, and increased total volume compared to the TSCI group. Additionally, this group had higher levels of antioxidant enzymes (GSH, SOD, CAT) and IL-10, and lower levels of pro-inflammatory cytokines (TNF-α, IL-1β) and MDA. Functional recovery, as reflected by Basso-Beattie-Bresnahan (BBB) scores, was significantly better in the CbH + Microsphere group across all time points post-injury. In conclusion, our findings suggest that CbH encapsulated with microspheres containing PMSCs-derived exosomes could enhance the prevention of injury spreading and the enhancement of pathological and behavioral symptoms when delivered to the location of spinal cord injury.