Mater Sci Eng C Mater Biol Appl. 2020 Feb;107

Motor and sensitive recovery after injection of a physically cross-linked PNIPAAm-g-PEG hydrogel in rat hemisectioned spinal cord.

Bonnet M1, Trimaille T2, Brezun JM1, Feron F3, Gigmes D2, Marqueste T1, Decherchi P4.
Author information
1
Aix Marseille Univ, CNRS, ISM, UMR 7287 ? Institut des Sciences du Mouvement: Etienne-Jules MAREY ?, Equipe ? Plasticit? des Syst?mes Nerveux et Musculaire ? (PSNM), Parc Scientifique et Technologique de Luminy, Facult? des Sciences du Sport de Marseille, CC910 - 163 Avenue de Luminy, F-13288, Marseille, Cedex 09, France.
2
Aix Marseille Univ, CNRS, ICR, UMR 7273 ? Institut de Chimie Radicalaire ?, Equipe ? Chimie Radicalaire Organique et Polym?res de Sp?cialit? ? (CROPS), Case 562 - Avenue Escadrille Normandie-Niemen, F-13397, Marseille, Cedex 20, France.
3
Aix Marseille Univ, CNRS, INP, UMR 7051 ? Institut de Neuropathophysiologie ?, Equipe ? G?nes, Rythmes et Neuropathophysiologie ? (GRN), 51, boulevard Pierre Dramard - CS80011, F-13344, Marseille, Cedex 15, France.
4
Aix Marseille Univ, CNRS, ISM, UMR 7287 ? Institut des Sciences du Mouvement: Etienne-Jules MAREY ?, Equipe ? Plasticit? des Syst?mes Nerveux et Musculaire ? (PSNM), Parc Scientifique et Technologique de Luminy, Facult? des Sciences du Sport de Marseille, CC910 - 163 Avenue de Luminy, F-13288, Marseille, Cedex 09, France. Electronic address: patrick.decherchi@univ-amu.fr.
Abstract
In line with experiments showing that implanted hydrogels are promising tools, we designed and injected, after a C2 spinal cord hemisection, a thermoresponsive and thermoreversible physically cross-linked poly(N-isopropylacrylamide)-poly(ethylene glycol) copolymer in order to reduce functional deficits and provide a favorable environment to axotomized axons. Nasal olfactory ecto-mesenchymal stem cells were cultured on the hydrogel in order to verify its biocompatibility. Then, inflammatory reaction (Interleukin-1β and 6, Tumor Necrosis Factor-α) was examined 15 days post-hydrogel injection. Functional recovery (postural and locomotor activities, muscle strength and tactile sensitivity) was assessed once a week, during 12 weeks. Finally, at 12 weeks post-injection, spinal reflexivity and ventilatory adjustments were measured, and the presence of glial cells and regenerated axons were determined in the injured area. Our results indicate that cells survived and proliferated on the hydrogel which, itself, did not induce an enhanced inflammation. Furthermore, we observed significant motor and sensitive improvements in hydrogel-injected animals. Hydrogel also induced H-reflex recovery close to control animals but no improved ventilatory adjustment to electrically-evoked isometric contractions. Finally, regrowing axons were visualized within the hydrogel with no glial cells colonization. Our results emphasize the effectiveness of our copolymer and its high therapeutic potential to repair the spinal cord after injury.

Copyright ? 2019 The Authors. Published by Elsevier B.V. All rights reserved.

KEYWORDS:
Biomaterial; Inflammation; Lesion; Reflex; Sensorimotor loop

https://www.ncbi.nlm.nih.gov/pubmed/31761180