1. Newly regenerated axons through a cell-containing biomaterial scaffold promote reorganization of spinal circuitry and restoration of motor functions with epidural electrical stimulation
- Author
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Peter J. Grahn, Dallece E. Curley, Michael J. Yaszemski, Priska Summer, Igor Lavrov, Tammy Strickland, Anthony J. Windebank, Nafis Akhmetov, Ahad M. Siddiqui, Shuya Zhang, Jarred J. Nesbitt, Bruce E. Knudsen, Bingkun K. Chen, Parita T. Suwan, Carlos A. Cuellar, Riazul Islam, Timur Latypov, Jodi L. Silvernail, Nicolas N. Madigan, and Emilee Manske
- Subjects
Scaffold ,medicine.anatomical_structure ,Neurotrophic factors ,Chemistry ,Spinal transection ,Cell ,Significant difference ,medicine ,Stimulation ,Biomaterial scaffold ,Biomedical engineering ,Microsphere - Abstract
We report the effect of newly regenerated neural fibers via bioengineered scaffold on reorganization of spinal circuitry and restoration of motor functions with electrical epidural stimulation (EES) after spinal transection (ST). Restoration across multiple modalities was evaluated for 7 weeks after ST with implanted scaffold seeded with Schwann cells, producing neurotrophic factors and with rapamycin microspheres. Gradual improvement in EES-facilitated stepping was observed in animals with scaffolds, although, no significant difference in stepping ability was found between groups without EES. Similar number of regenerated axons through the scaffolds was found in rats with and without EES-enabled training. Re-transection through the scaffold at week 6, reduced EES-enabled motor function, remaining higher compared to rats without scaffolds. The combination of scaffolds and EES-enabled training demonstrated synaptic changes below the injury. These findings indicate that sub-functional connectivity with regenerated across injury fibers can reorganize of sub-lesional circuitry, facilitating motor functions recovery with EES.
- Published
- 2020