Bonnet Maxime, Alluin Olivier, Trimaille Thomas, Gigmes Didier, Marqueste Tanguy, Decherchi Patrick
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.
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.
ACS Omega. 2020 Apr 27;5(18):10247-10259. doi: 10.1021/acsomega.9b03611. eCollection 2020 May 12.
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(-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 -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 -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.
脊髓损伤是一个主要的健康问题，会导致多种功能缺陷，并产生诸如损伤平面以下运动和感觉障碍等严重后果。迄今为止，所有修复策略均未取得成效。鉴于实验表明，植入的水凝胶，即天然或合成来源的免疫惰性生物材料，是很有前景的工具，为了减少功能缺陷、促进运动恢复并减轻痉挛，我们在严重的T10脊髓挫伤1周后，向损伤区域注射了一种热响应性物理交联的聚（异丙基丙烯酰胺）-聚（乙二醇）共聚物水凝胶。我们还研究了损伤后强化康复训练的效果。一组接受水凝胶注射的雄性Sprague-Dawley大鼠参加了为期8周的体育活动计划（每天15分钟，每周5天），以验证跑步机阶梯训练与水凝胶的联合使用是否能带来更好的效果。将获得的数据与仅接受盐水注射且有或没有进行相同体育活动计划的脊髓损伤动物所获得的数据进行比较。此外，为了验证我们设计的生物材料的生物相容性，在水凝胶注射后15天检查炎症反应（白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α）。从注射当天起，每周评估一次功能恢复情况（姿势和运动活动以及感觉运动协调），持续9周。最后，在注射9周后，测量脊髓反射性（-反射的速率依赖性抑制）。结果表明，水凝胶未引发额外的炎症。此外，我们观察到接受水凝胶注射的动物与接受训练的盐水注射动物在运动改善方面具有相同的显著效果。然而，与单独通过两种策略评估的恢复情况相比，水凝胶与运动的联合使用并未显示出更高的恢复效果。最后，发现水凝胶可诱导 -反射抑制恢复，运动也能在较小程度上诱导其恢复。然而，当两种策略联合使用时未观察到恢复效果。我们的结果突出了我们的共聚物的有效性及其在损伤后保护/修复脊髓方面的高治疗潜力。
