Effects of bioengineered scaffold loaded with neurotrophins and locomotor training in restoring H-reflex responses after spinal cord injury

The combinational effects of a bioengineered scaffold loaded with neurotrophins and rehabilitation training on spasticity observed after spinal cord injury (SCI) has not been studied. We used an animal model of moderate contusion injury at T9/T10 that received bioengineered scaffold poly N-isopropylacrylamide-g-poly ethylene glycol (PNIPAAm-g-PEG) loaded with BDNF/NT3 followed by body weight supported treadmill training (BWSTT) and assessed the efficacy of the combinational bioengineered approaches in treating spasticity. Five animal groups were included: Group 1: Sham, Group 2: Injury (SCI), Group 3: SCI + BWSTT (BWSTT), Group 4: SCI + PNIPAAm-g-PEG loaded with BDNF/NT3 (Transplant), and Group 5: SCI + PNIPAAm-g-PEG loaded with BDNF/NT3 + BWSTT (Combinational). Results indicate no significant changes in the BBB scores of animals among various groups, however, a significant restoration in the rate depression property of H-reflex was observed in both BWSTT and Combinational animals. Transplant group reported no improvement in the rate depression property of H-reflex and were similar to SCI only group. Histological findings report restoration of the chloride cotransporter (KCC2) labeling in both BWSTT and Combinational animals and down-regulation of KCC2 in both SCI and Transplant only animals. Findings from this study confirm that rehabilitation training is critical in restoring H-reflex responses and transplantation therapies alone cannot restore these responses after SCI. Also, although no significant difference was observed between the BWSTT and Combinational animals, comparable improvements in the two groups does open new pathways to exploring unique tissue-engineering approaches with promising clinical application for individuals with SCI.