Table 2.
A summary of animal model experiments (in vivo) on graphene and graphene-based materials in the repair of spinal cord injury
| Reference | Animals | Material intervention mode | Modeling method | Material intervention time | Detection method | Main results | Significance |
|---|---|---|---|---|---|---|---|
| Kolarcik et al., 2015 | Adult male Sprague-Dawley rats | Conductive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and multi-wall CNTs were coated on the electrode surface and doped with the anti-inflammatory drug dexamethasone | A unilateral laminectomy was performed to expose the left side of the dorsal root ganglion between L5 and L6 | 14 d | (1) Confocal fluorescent microscopy; | Significantly less neuronal death/damage was observed with coated electrodes and the inflammatory was also reduced. | This study was the first to report the utility of these coatings in stimulation applications. |
| (2) Immunofluorescence | |||||||
| López-Dolado et al., 2015 | Aged adult male Wistar rats | 3D flexible and porous scaffolds composed of partially rGO | A right lateral hemisection of approximately 8 mm3 (2 mm × 2 mm × 2 mm) at the C6 segment, rostral to the bulk of triceps brachii motoneurons | 10 d | (1) Histological examination; (2) Immunofluorescence | These structures facilitated regaining tissue integrity after SCI as early as 10 d and prevent the extension of the lesion. It had no local and systemic toxic responses. | This study was the first to implant 3D porous and flexible rGO scaffolds at the injured rat spinal cord. |
| López-Dolado et al., 2016 | Adult male Wistar rats | 3D scaffolds composed of partially rGO | A right lateral hemisection of approximately 8 mm3 (2 mm × 2 mm × 2 mm) at C6, rostral to the bulk of triceps brachii motoneurons | 30 d | (1) Histological examination; | The scaffolds in injury stabilization and sealing, moreover, rGO scaffolds supported angiogenesis. | This study investigated for the first time chronic tissue responses to 3D scaffolds composed of partially rGO when implanted in the injured rat spinal cord. |
| (2) Immunofluorescence; | |||||||
| (3) Transmission electron microscopy | |||||||
| Palejwala et al., 2016 | Wistar rats (19 males and 1 female) | Graphene nanoscaffolds were prepared by the mild chemical reduction of GO | Hemispinal cord transection at approximately the T2 level | 3 mon | (1) Electron microscopic; | The graphene nanoscaffolds adhered well to the spinal cord tissue. | Graphene is a nanomaterial that is biocompatible with neurons and may have significant biomedical application. |
| (2) Histological examination; | |||||||
| (3) Immunofluorescence | |||||||
| González-Mayorga et al., 2017 | Adult male Wistar rats | rGO microfibers as substrates for promoting nerve growth | A right lateral hemisection of approximately 8 mm3 (incomplete lesion) at C6, rostral to the bulk of triceps brachii motoneurons. | 10 d | (1) Scanning electron microscope; | In vivo studies reveal the feasible implantation of these rGO microfibers as a guidance platform in the injured rat spinal cord, without evident signs of subacute local toxicity. | These positive findings boost further investigation for enhancing repair in the damaged central neural tissue including the injured spinal cord. |
| (2) Transmission electron microscopy; | |||||||
| (3) Immunofluorescence | |||||||
| Domínguez-Bajo et al., 2019 | Adult male rats | 3D randomly porous foams have been prepared in mechanical compliance with neural cells and tissues (Young’s modulus of 1.3 ± 1.0 kPa) as demonstrated by atomic force microscopy techniques applied ex vivo. | A cervical unilateral hemisection at the right C6, rostral to the bulk of triceps brachii motoneurons | 4 mon | (1) Transmission electron microscopy; | The scaffolds significantly reduced perilesional damage and caused no compressive damage in the contralateral hemicord and rostral/caudal regions. It also does not either alter the rat spontaneous behavior or induce toxicity in major organs. | This study suggests hints of rGO sheets dissociation and eventual degradation at the injured spinal cord for the first time. |
| (2) Magnetic resonance imaging; | |||||||
| (3) Atomic force microscopy; | |||||||
| (4) Immunofluorescence; | |||||||
| (5) Histological examination; | |||||||
| (6) Behavioral tests | |||||||
| Pan et al., 2019 | Female Sprague-Dawley rats | IGF-1 and BDNF were successfully immobilized on biodegradable GO-incorporated PLGA electrospun nanofibres. | T9 spinal cord hemisection rat model | 4 wk | (1) Immunofluorescence; | Local delivery of IGF-1 and BDNF immobilized to PLGA/GO nanofibres significantly improved functional locomotor recovery, reduced cavity formation and increased the number of neurons at the injury site. | This study indicated that PLGA/GO is an effective carrier for IGF-1 and BDNF delivery. |
| (2) Motor function detection; | |||||||
| (3) Histology observations; | |||||||
| (4) The BBB locomotor rating scale; | |||||||
| (5) Motor evoked potential detection | |||||||
| Domínguez-Bajo et al., 2020 | Adult male rats | rGO materials in the shape of microfibers | A right hemisection at C6 cervical level, rostral to the bulk of triceps brachii motoneurons | 10 d | (1) Behavioural tests; | These findings outline the potential of rGO-MF-based scaffolds to promote regenerative features at the injured spinal cord such as axonal and vascular growth. | In this work, the regenerative potential of rGO-MFs when chronically interfaced with a cervical spinal cord injury was investigated for the first time. |
| (2) Immunofluorescence | |||||||
| Yang et al., 2021 | Female Sprague-Dawley rats | A conductive GO composited chitosan scaffold was fabricated by genipin crosslinking and lyophilization. | The lamina of the thoracic vertebrae T8–T10 were exposed. The spinal cord was exposed and approximately 2 mm of the spinal cord tissue at the T9 level was completely removed under an operating microscope | 10 wk | (1) The BBB locomotor rating scale; | GO could have a positive role in the recovery of neurological function after SCI by promoting the degradation of the scaffold, adhesion, and migration of nerve cells to the scaffold. | The scaffold can promote the repair of damaged nerve tissue. |
| (2) Electrophysiologic recording; | |||||||
| (3) Histological analysis; | |||||||
| (4) Immunofluorescence |
BBB: Basso, Beattie, and Bresnahan; BDNF: brain-derived neurotrophic factor; CNTs: Carbon nanotubes; IGF-1: Insulin-like growth factor 1; min: minute; PLGA: poly (lactic-co-glycolic acid); rGO-MFs: reduced graphene oxide materials in the shape of microfibers; SCI: spinal cord injury.