Table 5.

Drugs used as antiscarring agents.

Reference	Method to Induce Scar Formation	Agent	Animal and Nerve model	Analyses	Results
Mekaj et al., 2017 [36]	Section + suture	Tacrolimus (FK506)	Male European Rabbit Sciatic nerve	-Gross evaluation (Petersen’s classification) (12 weeks) -Muscle wet weight (12 weeks) -Histology on nerve and surrounding tissue (H&E, Masson’s trichrome) -Fibroblast and inflammatory cell counts (12 weeks) -Nerve IHC (S100) (12 weeks)	Scar reduction around the nerve, both macroscopically and microscopically. Increased nerve diameter. Higher gastrocnemius mass. Improved microstructural organization. Higher expression of S100.
Zhu et al., 2017 [61]	Silicone tube around the nerve	Decompression and chondroitinase ABC (6 weeks after compression injury)	Male Sprague–Dawley Rat and Male C57BL/6 Mouse Sciatic nerve	-Electrophysiology (1 month) -RNA (neuron-glial antigen 2, phosphacan, brevican, versican, aggrecan, and decorin) and protein expression (decorin, aggrecan, laminina 2, collagen IV, and fibronectin) (1 month) -Nerve IHC (decorin, aggrecan, laminina 2, collagen IV, and fibronectin) (1 month)	Surgical decompression alone does not reverse the functional changes to the nerve, whereas the administration of chondroitinase-ABC, in addition to decompression, resulted in functional improvement.
Vural et al., 2016 [41]	Abrasion	Mitomycin C/ Daunorubicin	Male Wistar Rat Sciatic nerve	-Gross evaluation (Petersen’s classification) (8 weeks) -Histology on nerve and surrounding tissue (H&E and Masson’s trichrome—fibroblast count) (8 weeks)	Macroscopically, mitomycin C, and daunorubicin decreased adhesion. Scar tissue thickness and fibroblast/fibrocyte cell number were reduced.
Xue et al., 2016 [60]	Section + suture	Verapamil (calcium channel blockers)	Sprague–Dawley Rat Sciatic nerve	-Gross evaluation (qualitative evaluation) (4 and 12 weeks) -Nerve IHC (collagen I) (4 and 12 weeks) -Ultrastructural evaluation (TEM) (4 and 12 weeks) -Hydroxyproline and collagen assay (4 and 12 weeks)	The collagen content of nerve scar was apparently less than that of the control group; more cytoplasmic vesicles in the fibroblasts of the treated group were observed.
Kaplan et al., 2014 [78]	Section + suture	Citicoline	Female Wistar Albino Rat Sciatic nerve	-Functional evaluation (SFI) (4, 8, 12 weeks) -Electromyography (12 weeks) -Gross evaluation (Petersen’s classification) (12 weeks) -Histology on nerve and surrounding tissue (Masson’s trichrome and Toluidine Blue for morphometrical analysis) (12 weeks)	Improvement of SFI. Significant reduction in scarring. Significant increase in myelinated axons in C900 and reduction of scar in the treated group.
Que et al., 2013 [58]	Section + suture	Tacrolimus (FK506)	Male Sprague–Dawley Rat Sciatic nerve	-Nerve IHC (TGF-β) (4 weeks) -Histology on nerve and surrounding tissue (Masson’s trichrome) (4 weeks) -In vitro analysis	FK506 has a valid effect on scar formation reduction in sciatic nerve-injured rat by inducing fibroblast apoptosis.
Ngeow et al., 2011 [50]	Section + suture	Triamcinolone acetonide, Interleukin-10 (IL 10), mannose-6-phosphate (M6P)	C57 Black-6 Mouse Sciatic nerve	-Electrophysiological evaluation (6 and 12 weeks) -Functional evaluation (CatWalk) (1, 3, 6, 9, and 12 weeks -Histology on nerve and surrounding tissue (Picrosirius staining) (6 and 12 weeks)	The percentage of scarring was not significantly different between methods in microscopical analysis. Reduction of compound action potential in triamcinolone and M6P 200 was observed through EMG.
Ngeow et al., 2011 [51]	Section + suture	Mannose-6-phosphate	C57 Black-6 mice Sciatic nerve	-Electrophysiological evaluation (6 and 12 weeks) -Histology on nerve and surrounding tissue (Picrosirius staining) (6 and 12 weeks) -Functional evaluation (CatWalk) (1, 3, 6, 9 and 12 weeks	Larger compound action potential and better functional recovery in early evaluation. Reduction in collagen staining.
Aslan et al., 2011 [56]	Section + suture (immediate or 3 days later)	CDP-choline, cytidine, choline, or cytidine–choline (during nerve repair)	Female Sprague–Dawley Rat Sciatic nerve	-Functional evaluation (SFI) (4, 8, 12 weeks) -Gross evaluation (Petersen’s classification) (12 weeks) -Histology on nerve and surrounding tissue (H&E, Weil method for morphometrical analysis) (12 weeks)	Treatment with CDP-choline or cytidine–choline reduced scar formation and decreased nerve adherence.
Albayrak et al., 2010 [30]	Abrasion	Doxorubicin	Male Wistar Albino Rat Sciatic nerve	-Gross evaluation (Petersen’s classification) (12 weeks) -Histology on nerve and surrounding tissue (Toluidine Blue) (12 weeks) -Ultrastructural evaluation (TEM) (12 weeks)	Topical application of doxorubicin effectively reduced epineural scar formation.
Atkins et al., 2007 [53]	Section + suture	IL-10	C57 Black-6 MouseSciatic nerve	-Electrophysiological analysis (6 weeks) -Histology on nerve and surrounding tissue (Picrosirius staining and Toluidine Blue for morphometrical analysis) (6 weeks)	Compound action potential and area of staining for collagen not significantly different compared to controls. Higher number of myelinated fibers compared to control but no difference with the other groups.
Ozay et al., 2007 [31]	Section + suture	Citicoline	Female Sprague-Dawley Rat Sciatic nerve	-Functional evaluation (SFI) (4, 8, 12 weeks) -Electrophysiological analysis (4, 12 weeks) -Gross evaluation (Petersen’s classification) (4 weeks) -Histology on nerve and surrounding tissue (Masson’s trichrome, H&E, Weil method for morphometrical analysis) (4, 12 weeks)	Rats treated with citicoline showed significantly better SFI and improvement at 12 weeks of electromyography. Nerves were surrounded by only a very thin, lucent membrane and showed thin dark bands of connective tissue surrounding the nerve.
Ilbay et al., 2005 [32]	Scratch	Mitomycin C	Male Wistar Rat Sciatic nerve	-Gross evaluation (Petersen’s classification) (4 weeks) -Histology on nerve and surrounding tissue (H&E, Masson’s trichrome— fibroblasts/fibrocytes count) (4 weeks)	Macroscopical and microscopical reduction of perineural adhesions in the treated groups; lower number of fibroblast/fibrocytes.
Gorgulu et al., 1998 [33]	External neurolysis, abrasive injury, anastomosis	Aprotinin	Male Sprague-Dawley RatSciatic nerve	-Functional analysis (sciatic nerve function) (weekly) -Gross evaluation (Petersen’s classification) (4, 6 weeks) -Histology on nerve and surrounding tissue (Masson’s trichrome) (4, 6 weeks)	Scar reduction after aprotinin application. No differences in neurological tests were observed.