NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury

Proceedings of the National Academy of Sciences of the United States of America
Jia-Sheng RaoXiaoguang Li

Abstract

Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.

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Citations

Aug 17, 2018·Journal of Biomaterials Applications·Ashley E MohrmanNic D Leipzig
May 31, 2019·Journal of Medical Primatology·Jia-Sheng RaoXiao-Guang Li
Mar 12, 2020·Tissue Engineering. Part a·Veronica A RevkovaVladimir P Baklaushev
Apr 2, 2019·Experimental Animals·Rui-Han WeiXiao-Guang Li
Apr 9, 2020·Frontiers in Bioengineering and Biotechnology·Fengxuan HanBin Li
May 21, 2020·Frontiers in Bioengineering and Biotechnology·Doddy Denise Ojeda-HernándezJuan C Mateos-Díaz
Jan 27, 2019·Tissue Engineering. Part a·Wei Liu, Yilin Cao
Jun 28, 2019·Frontiers in Cellular Neuroscience·Hiroyuki KatohMichael G Fehlings
Sep 19, 2019·Surgical Neurology International·Xiaoping RenSergio Canavero
Oct 23, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Petr KrupaIgor A Lavrov
Nov 4, 2020·Expert Opinion on Therapeutic Targets·A S de MirandaAntonio Lucio Teixeira
Dec 4, 2020·Tissue Engineering. Part B, Reviews·Jiao Jiao LiBin Zhao
Mar 6, 2021·Materials Today. Bio·D SilvaA J Salgado
Jul 25, 2021·Advanced Drug Delivery Reviews·Shuting S CaiKam W Leong
Jul 10, 2021·Science Progress·Can ZhaoJia-Sheng Rao

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