Table 3.
Studies on CS-based scaffolds for nerve tissue regeneration.
| Authors | Scaffold type | Study outline | Results | Conclusion |
|---|---|---|---|---|
| Simões et al. 2011 [72] | High MW CS membranes crosslinked with GPTMS. (DA: NA; ratio: NA) | In vitro: CC in neuroblastoma clone cell culture (N1E-115); fluorescence microscopy for intracellular Ca++ In vivo: HT analysis of the subcutaneous tissue in adult Wistar rats. No control group Sample (in vivo): n = 4 |
CS membranes promoted cell adhesion and differentiation in vitro In vivo: slight to intense chronic inflammation was observed in HT analysis Presence of fibrous capsule |
Authors concluded that CS membranes demonstrated biocompatibility and potential for use in the regeneration of nerve tissue However, the presence of chronic inflammation and fibrous capsules contradict the conclusion (P < 0.05) |
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| Wei et al. 2011 [73] | CS (MW 1800 kDa; DA 6.5%) + SF films (ratios: 50 : 50 or 70 : 30) impregnated with SC | In vitro: CC in SC culture and Schwann cells In vivo: implantation of scaffolds in lesions of the sciatic nerve in adult Sprague-Dawley rats; functional and HT evaluation Control group: nongrafted rats Sample: n = 8 |
In vitro: greater adhesion and proliferation with CS and SF scaffolds when compared to pure CS In vivo: Greater functional recovery and tissue regeneration in the groups with CS+SF impregnated with SC |
CS+SF impregnated with SC promoted better regeneration in sciatic nerve lesions and lower proliferation of fibrous scar tissue (P < 0.05) |
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| Chen et al. 2011 [74] | CS conduits (DA 7.7%; MW 22 kDa) whether or not impregnated with BMMSC | In vivo: implantation of conduits in spinal cord defects in adult Sprague-Dawley rats; functional evaluation and electromyography; HT and IHC analyses Control group: untreated defects Sample: n = 15 Control: n = 10 |
Better motor and electromyographic response with CS+BMSC; better macroscopic and HT regeneration of defects filled with scaffolds with SC | CS +SC scaffolds were capable of promoting axonal regeneration, remyelination, and functional recovery after sectioning of spinal cord (P < 0.05) |
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| Liao et al. 2012 [75] | CS in the form of conduits (DA 15–25%; MW: NA), either with or without SC impregnation | In vivo: implantation of scaffolds in sciatic nerve defects in adult Sprague-Dawley rats; evaluation of repair through magnetic resonance, functional evaluation, and HT analyses. Control group not specified Sample: n = 18 |
Nerves implanted with scaffolds impregnated with MSC demonstrated better functional recovery and better magnetic resonance results than acellular scaffolds | CS impregnated with SC promoted regeneration of nerve tissue; magnetic resonance was effective for evaluating regeneration of the sciatic nerve (P < 0.05) |
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| Xue et al. 2012 [76] | CS+PLGA (ratio NA) in the form of tubes, whether or not impregnated with SC (DA: NA; MW: NA) | In vivo: grafting of conduits on to sciatic nerve defects in adult Beagle dogs; functional and electroneuromyographic evaluations and neuron count; morphometric analysis and HT analysis of associated muscles Control groups: nongrafted and autogenous grafted defects Sample: n = 5 |
Better functional recovery in CS+PLGA+SC group; remyelination and recovery of nerve diameter; histologically, greater regeneration in the autogenic and CS+PLA+SC groups | CS+PLGA scaffold, either with or without stem cells, favored regeneration of extensive sciatic nerve lesion and showed viability of carrying out a clinical study with this material (P < 0.05) |
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| Xiao et al. 2013 [77] | CS+COL (ratio: 1 : 4) in the form of conduits, whether or not combined with RGD peptide (DA: NA; MW: NA) |
In vivo: implantation of scaffolds in segmental defects of adult Sprague-Dawley rats sciatic nerves; functional evaluation via electroneuromyography, neuron markers, and histology Control groups: untreated defects and autogenous grafted defects Sample: n = 8 |
CS+COL scaffolds showed better functional recovery than negative control; CS+COL+RGD showed greater management of nerve stimuli than negative control, but lower than the autogenous control. Scaffolds demonstrated greater tissue regeneration than negative control but less than the positive control | CS+COL+RGD was capable of accelerating the regeneration of the sciatic nerve, obtaining satisfactory results in 2 months (P < 0.05) |
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| Biazar and Keshel 2013 [78] | CS (medium MW; DA 15–25%) in the form of conduits, whether or not crosslinked with PHBV | In vitro: CC in Schwann cell culture In vivo: implantation of scaffolds in sciatic nerve defects of 4–8-week-old Wistar rats; macroscopic and microscopic analyses via HT and IHC Control groups: untreated defects and autogenous grafted defects Sample: n = 5 |
In vitro: CS+PHBV was found to exhibit greater cell viability and proliferation In vivo: CS (crosslinked or not with PHBV), produced regeneration results far superior to the negative control, though inferior to the autogenous control |
CS+PHBV demonstrated capacity to regenerate lesions of the sciatic nerve in rats (P < 0.05), having potential for application in tissue engineering and clinical studies |
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| Gu et al. 2014 [30] | CS+SF (ratio NA) in the form of conduits impregnated with EMC (DA: NA; MW: NA) | In vitro: isolation of Schwann cell EMC derived from rats In vivo: implantation in sciatic nerve defects in adult Sprague-Dawley rats; HT and IHC analyses; electrophysiological tests Control group: acellular xenogeneic nerve graft Sample: not specified |
In vivo: better nerve tissue regeneration and density in the CS+SF+EMC group after 12 weeks. The electrophysiological tests got a response in all groups, though to a lesser extent in the CS+SF group | The CS+SF+EMC scaffold was effective in regenerating nerve tissue (P < 0.05) |
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| Wang et al. 2016 [79] | CS conduits (DD 92.3%; MW 250 kDa) or chitooligosaccharides (COS) in silicon conduits | In vitro: CS biodegradation and CC in Schwann cell culture In vivo: implantation of scaffolds in lesions of the sciatic nerves of adult Sprague-Dawley rats; HT and IHC analyses Control: saline group Sample: not specified |
In vitro: COS promoted greater cell proliferation and differentiation In vivo: greater expression of nerve cell markers in the chitooligosaccharide groups |
Chitooligosaccharides promote nerve cell proliferation and differentiation, stimulating regeneration of nerve tissue (P < 0.05/P < 0.01) |
BMMSCs: bone marrow mesenchymal stem cells; CC: cytocompatibility; COL: collagen; COS: chitooligosaccharides; CS: chitosan; DA: degree of acetylation; ECM: extracellular matrix; GPTMS: glycidoxypropyltrimethoxysilane; HT: histological; IHC: immunohistochemical; kDa: kilodaltons; MW: molecular weight; PLGA: polylactic-co-glycolic acid; RGD: cell-adhesive peptide; SC/BMSC: stem cells/bone marrow stem cells; SF: silk fibroin.