Delayed Injection of a Physically Cross-Linked PNIPAAm- g-PEG Hydrogel in Rat Contused Spinal Cord Improves Functional Recovery

Maxime Bonnet; Olivier Alluin; Thomas Trimaille; Didier Gigmes; Tanguy Marqueste; Patrick Decherchi

doi:10.1021/acsomega.9b03611

Delayed Injection of a Physically Cross-Linked PNIPAAm- g-PEG Hydrogel in Rat Contused Spinal Cord Improves Functional Recovery

ACS Omega. 2020 Apr 27;5(18):10247-10259. doi: 10.1021/acsomega.9b03611. eCollection 2020 May 12.

Authors

Maxime Bonnet¹, Olivier Alluin¹, Thomas Trimaille², Didier Gigmes², Tanguy Marqueste¹, Patrick Decherchi¹

Affiliations

¹ Aix Marseille Univ, CNRS, ISM, UMR 7287, Institut des Sciences du Mouvement: Etienne-Jules MAREY, Equipe, Plasticité des Systèmes Nerveux et Musculaire, (PSNM), Parc Scientifique et Technologique de Luminy, Faculté 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 Polymères de Spécialité, (CROPS), Case 562-Avenue Escadrille Normandie-Niemen, F-13397 Marseille Cedex 20, France.

Abstract

Spinal cord injury is a main health issue, leading to multiple functional deficits with major consequences such as motor and sensitive impairment below the lesion. To date, all repair strategies remain ineffective. In line with the experiments showing that implanted hydrogels, immunologically inert biomaterials, from natural or synthetic origins, are promising tools and in order to reduce functional deficits, to increase locomotor recovery, and to reduce spasticity, we injected into the lesion area, 1 week after a severe T10 spinal cord contusion, a thermoresponsive physically cross-linked poly(N-isopropylacrylamide)-poly(ethylene glycol) copolymer hydrogel. The effect of postinjury intensive rehabilitation training was also studied. A group of male Sprague-Dawley rats receiving the hydrogel was enrolled in an 8 week program of physical activity (15 min/day, 5 days/week) in order to verify if the combination of a treadmill step-training and hydrogel could lead to better outcomes. The data obtained were compared to those obtained in animals with a spinal lesion alone receiving a saline injection with or without performing the same program of physical activity. Furthermore, in order to verify the biocompatibility of our designed biomaterial, an inflammatory reaction (interleukin-1β, interleukin-6, and tumor necrosis factor-α) was examined 15 days post-hydrogel injection. Functional recovery (postural and locomotor activities and sensorimotor coordination) was assessed from the day of injection, once a week, for 9 weeks. Finally, 9 weeks postinjection, the spinal reflexivity (rate-dependent depression of the H-reflex) was measured. The results indicate that the hydrogel did not induce an additional inflammation. Furthermore, we observed the same significant locomotor improvements in hydrogel-injected animals as in trained saline-injected animals. However, the combination of hydrogel with exercise did not show higher recovery compared to that evaluated by the two strategies independently. Finally, the H-reflex depression recovery was found to be induced by the hydrogel and, albeit to a lesser degree, exercise. However, no recovery was observed when the two strategies were combined. Our results highlight the effectiveness of our copolymer and its high therapeutic potential to preserve/repair the spinal cord after lesion.