Tubular scaffold with microchannels and an H‐shaped lumen loaded with bone marrow stromal cells promotes neuroregeneration and inhibits apoptosis after spinal cord injury

Abstract

As a result of its complex histological structure, regeneration patterns of grey and white matter are quite different in the spinal cord. Therefore, tissue engineering scaffolds for repairing spinal cord injury must be able to adapt to varying neural regeneration patterns. The aim of the present study was to improve a previously reported spinal cord‐mimicking partition‐type scaffold by adding microchannels on a single tubular wall along its longitudinal axis, thus integrating the two architectures of a single H‐shaped central tube and many microchannels. Next, the integrated scaffold was loaded with bone marrow stromal cells (BMSCs) and transplanted to bridge the 5‐mm defect of a complete transverse lesion in the thoracic spinal cord of rats. Subsequently, effects on nerve regeneration, locomotion function recovery, and early neuroprotection were observed. After 1 year of repair, the integrated scaffold could guide the regeneration of axons appearing in the debris of degraded microchannels, especially serotonin receptor 1A receptor‐positive axonal tracts, which were relatively orderly arranged. Moreover, a network of nerve fibres was present, and a few BMSCs expressed neuronal markers in tubular lumens. Functionally, electrophysiological and locomotor functions of rats were partially recovered. In addition, we found that BMSCs could protect neurons and oligodendrocytes from apoptosis during the early stage of implantation. Taken together, our results demonstrate the potential of this novel integrated scaffold loaded with BMSCs to promote spinal cord regeneration through mechanical guidance and neuroprotective mechanisms.

Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis

“…For example, Chen et al (2020b) showed the regenerative effect of BMSCs seeded into a chitosan tubular scaffold combining the two architectures of a single H-shaped central tube and several microchannels. The scaffold was implanted to bridge the 5-mm defect of a complete transverse lesion in the thoracic spinal cord of rats, and when compared with the empty scaffold, the BMSC enhanced functional improvement and the number of regenerating axons and elicited antiapoptotic effects ( Chen et al, 2020b ).…”

“…For example, Chen et al (2020b) showed the regenerative effect of BMSCs seeded into a chitosan tubular scaffold combining the two architectures of a single H-shaped central tube and several microchannels. The scaffold was implanted to bridge the 5-mm defect of a complete transverse lesion in the thoracic spinal cord of rats, and when compared with the empty scaffold, the BMSC enhanced functional improvement and the number of regenerating axons and elicited antiapoptotic effects ( Chen et al, 2020b ). Peng et al (2018) showed that rat MSCs combined with a nerve-guide collagen scaffold inhibited chronic scar formation, provided linear guidance for the nerves, and promoted M2 polarization to form an anti-inflammatory environment in a hemisected SCI rat model ( Peng et al, 2018 ).…”

EphB2 knockdown decreases the formation of astroglial‐fibrotic scars to promote nerve regeneration after spinal cord injury in rats

“…This may also explain why the functional recovery was limited while there were a substantial number of regenerating nerve fibers in the present study. Therefore, combinational strategies may be achieved better therapeutic effects, 37 as shown by our group recently 38 …”

Hydrogels in Spinal Cord Injury Repair: A Review

“…The smoothness and convexity of the scaffold surface can affect protein expression ( Johnson et al, 2018 ). Animal experiments have shown that the scaffold morphology can promote cell migration and axon regeneration ( Chen et al, 2020 ). Currently, most research on SCI repair is focused on modifying traditional hydrogels, and efforts to further strengthen the therapeutic effect of hydrogels, promote the regeneration of nerve stumps, and rebuild neural circuits should focus on modifying traditional hydrogels and developing new hydrogels with optimized mechanical properties, drug encapsulation and sustained release activities, and the ability to load cellular molecules and drugs ( Xu et al, 2013 ; Ucar et al, 2021 ; Yao et al, 2021 ).…”