Chitosan conduits for peripheral nerve repair: a systematic review of animal studies

Fagundes, T. P.; Caetano, G. A.; Ribas, V. T.; Calderaro, D. C.; Castro, U. B.

doi:10.1590/1519-6984.280569

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Original Article • Braz. J. Biol. 84 • 2024 • https://doi.org/10.1590/1519-6984.280569 linkcopy

Chitosan conduits for peripheral nerve repair: a systematic review of animal studies

Condutos de quitosana para reparo de nervos periféricos: uma revisão sistemática de estudos em animais

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Peripheral nerve injuries are major causes of disability worldwide. The current standard treatment, autologous nerve grafting, puts the donor region at risk and has limited availability. A systematic search of MEDLINE, EMBASE, and Web of Science databases for studies published between January 1, 2008, and September 04, 2024, was performed to compare interventions using chitosan tubes with non-intervention or autologous nerve grafts in rats with artificially injured sciatic nerves. Twenty-one experimental studies including 738 animals were selected. Nerve repair using chitosan conduits resulted in a higher sciatic functional index compared to non-intervention. Higher conduction velocity and a greater number of myelinated fibers were observed in nerve fibers treated with chitosan compared to the no intervention or primary repair groups. However, compound muscle action potentials and somatosensory evoked potentials were superior in the latter compared to nerves treated with the polymer.

Keywords:
nerve regeneration; biomaterials avaliability; animal model; suture; eletrical stimulation

Database	Search Strategy	Search Terms	Time Frame	Results
PubMed	((“Peripheral Nervous System Diseases”[Mesh]) AND “Chitosan”[Mesh]) AND “Models, Animal”[Mesh]	“Peripheral Nervous System Diseases”, “Chitosan”, “Models, Animal”	2008 - September 2024	12
Embase	#1 AND (2008:py OR 2010:py OR 2011:py OR 2012:py OR 2013:py OR 2014:py OR 2015:py OR 2016:py OR 2017:py OR 2018:py OR 2019:py OR 2020:py OR 2021:py OR 2022:py OR 2023:py OR 2024:py)	'chitosan'/exp OR chitosan AND 'peripheral nerve injury'/exp OR 'peripheral nerve injury' AND 'animal model'/exp OR 'animal model'	2008 - September 2024	79
Web of Science	chitosan AND “peripheral nerve injury” AND animal AND models	“Chitosan”, “Peripheral Nerve Injury”, “Animal”, “Models”	2008 - September 2024	10
Grey Literature	Repositório Institucional UFMG	“Chitosan”, “Peripheral Nerve Injury”, “Animal Models”	2008 - September 2024	-

T(s) and Year	N	Material and Intervention	Comparison/Control Group	Follow-up	Electromyographic Improvement	Histological Improvement	Walking Track (SFI)
Shapira et al. (2016)	21	CNC (11)	ANG (10)	0, 30, and 90 days	No statistically significant difference in latency (1.39 ms vs. 1.63 ms; p=0.48) and amplitude (6.28 mv vs. 6.43 mv; p=0.8)	No difference in number and size of myelinated fibers	No difference between groups (P = 0.177)
Azizi et al. (2014)	90	CNC + Vit E (15); CNC + PQQ (15); CNC + PQQ + Vit E (15); CNC (15)	TC (15); Sham (15)	4, 8, and 12 weeks	% of sciatic conduction velocity recovery: (A) 42% (B) 34% (C) 54%; 17% in group D (p < 0.05); <10% in control group	Groups A, B, and C presented greater nerve fiber, axon diameter, and myelin sheath thickness	Experimental groups had greater SFI than TC in all evaluations
Ilkhanizadeh et al. (2017)	60	CNC + BMMC (15)	Sham (15); nerve suture (15); CNC + saline (15)	4, 8, and 12 weeks	Not evaluated	Rats treated with BMMC had significantly greater nerve fiber, axon diameter, and myelin sheath thickness	At 12 weeks: mean SFI in CNC + BMMC: ~-17.5 versus –26 in CNC + saline group (p < 0.05)
Dietzmeyer et al. (2019)	32	Two-chambered CNC (8); Two-chambered corrugated CNC (8)	Standard CNC (8); ANG (8)	16 weeks	Full recovery in C2. CMAPs: no difference in treated rats compared to controls after 16 weeks. Higher amplitudes obtained in C2 group	C1 and C2 showed thicker tissue cables and higher number of regrown axons within the distal graft compared to groups A and B	Not evaluated
Liu et al. (2019)	150	Chitosan only (30); Chitosan + mPEG-PELG (30); Chitosan + NGF/IM (30); Chitosan/mPEG-PELG (30)	ANG (30)	12 and 24 weeks	ANG and group D association had higher CMAP amplitude and motor NCV than other groups	Group D showed greater number of regenerating fibers and thickness of myelin sheath than A, B, and C, but comparable results to ANG group	Rats in group D achieved a superior SFI. No statistical difference with the control group
Azizi et al. (2015)	45	CNC with alpha-lipoic acid (15)	CNC + saline solution (15); Sham (15)	4, 8, and 12 weeks	NCV at 12 weeks (group A vs B): 39% ± 1.8% vs 26.5% (P < 0.05); recovery index at 12 weeks: 0.29 ± 0.02 vs 0.25 ± 0.03 (p <0.05)	Group A showed greater nerve fibers and axon diameter, and myelin sheath thickness than control group (P < 0.05) at 8 and 12 weeks	Functional recovery assessed through SFI was faster in experimental group at 4 and 8 weeks after surgery
Raisi et al. (2012)	60	CNC (15)	Silicone conduit (15); Sham (15); TCI (15)	4, 8, and 12 weeks	NCV at 12 weeks in experimental groups were higher than in control. Group A: 28% vs 28.5% in group B. Transected control: 4% (p < 0.05)	The number of nerve fibers and mean diameter of fibers in experimental group were higher than in TC group	Better SFI for rats in group A than in control (p < 0.05)
Carvalho et al. (2018)	26	CNCs (19)	ANG (7)	12 weeks	ANG showed increased recovery with 100% and 71% evocable CMAPs from tibialis anterior and plantar muscles. Only 5 animals from CNC groups displayed evocable CMAPs	ANG displayed thick and complete nerve bridge. CNC 25:75 displayed thin but continuous nerve cable	Not evaluated
Duda et al. (2014)	36	COM (12); CNC (12)	ANG (12); ANG (long term) (17)	2 and 13 weeks	No statistically significant intergroup differences. ANG had highest CMAP amplitude followed by CNC and COM. NCV ratio significantly reduced for COM compared to ANG	Nerve fiber density significantly higher in ANG group. Artificial grafts comparable to ANG in myelin thickness	Not evaluated
Haastert-Talini et al. (2013)	141	DAI (17); DAII (17); DAIII (17)	ANG	13 weeks	No significant differences among amplitudes of evocable CMAPs between groups	Only total numbers of myelinated fibers distal from DAI significantly higher compared to ANG group (p<0.05). No statistical differences in axon and fiber diameters and myelin thickness	Not evaluated
Sun et al. (2024)	24	Curcumin in keratin-chitosan hydrogels (12)	ANG (12)	10, 30, and 90 days	Not evaluated	Increase in myelin sheath thickness, higher number of myelinated fibers	Significant improvement in SFI
Zhang et al. (2024)	30	Alginate microgels with VEGF and BDNF + chitosan conduits (15)	Control (15)	12 weeks	Significant increase in CMAP amplitude (p < 0.05)	Increase in myelin thickness and axon diameter	SFI improved at all evaluated times
Jafarisavari et al. (2024)	25	PCL-chitosan nanofibrous conduits with piracetam and vitamin B12 (15)	ANG (10)	4, 8, and 12 weeks	Not evaluated	Larger axonal diameter and myelin thickness compared to control	SFI significantly improved (p < 0.05)
Al-Haideri and Al-Timmemi (2024)	28	Chitosan conduits with nanoparticles (14)	Control (14)	56 and 112 days	Increase in NCV compared to control (p < 0.05)	Increase in myelin thickness and number of myelinated fibers	SFI improved compared to control
Xue et al. (2024)	40	Skin-derived precursors induced into Schwann cells + chitosan/silk conduits (20)	Control (20)	90 days	Not evaluated	Increase in axon number and myelin sheath thickness	SFI significantly improved compared to control (p < 0.05)
Li et al. (2024)	30	Chitosan conduits with BDNF (15)	ANG (15)	12 weeks	Increase in CMAP amplitude (p < 0.05)	Increase in myelin thickness and axon diameter compared to control	SFI significantly improved (p < 0.05)
Zhang et al. (2023)	35	Nanofibrous scaffolds containing chitosan, ADSCs, and NGF (20)	Control (15)	5 weeks	Increase in NCV and CMAP (p < 0.05)	Increase in myelin sheath thickness and axon diameter	SFI improved compared to control
Jiang et al. (2023)	25	O-carboxymethyl chitosan conduits (13)	ANG (12)	10, 30, and 90 days	Not evaluated	Increase in myelin sheath thickness, higher number of myelinated fibers	Significant improvement in SFI
Qi et al. (2023)	24	Bionic chitosan graft (12)	Control (12)	4, 8, and 12 weeks	Not evaluated	Larger axonal diameter and myelin thickness compared to control	SFI significantly improved (p < 0.05)
Wang et al. (2023)	28	Chitosan scaffold with esterase release (14)	Control (14)	56 and 112 days	Increase in NCV compared to control (p < 0.05)	Increase in myelin thickness and number of myelinated fibers	SFI improved compared to control
Li et al. (2023)	28	Sustained release microspheres of NGF and BDNF in chitosan conduits (14)	Control (14)	56 and 112 days	Increase in NCV compared to control (p < 0.05)	Increase in myelin thickness and number of myelinated fibers	SFI improved compared to control

Study	Was the allocation sequence adequately generated and applied?	Were the groups similar at baseline or adjusted for confounders?	Was the allocation adequately concealed?	Were the animals randomly housed during the experiment?	Were the caregivers and/or investigators blinded?	Were animals selected at random for outcome assessment?	Was the outcome assessor blinded?	Were incomplete outcome data adequately addressed?	Was the study free of other problems that could result in high risk of bias?
Shapira et al. (2016)	NO	YES	YES	YES	YES	YES	YES	NO	NO
Azizi et al., (2014)	NO	NO (RANDOMLY ASSIGNED, METHODS NOT DESCRIBED)	YES	YES	YES	YES	YES	NO	NO
Ilkhanizadeh et al. (2017)	NO	YES	YES	YES	YES	YES	YES	NO	NO
Dietzmeyer et al. (2019)	NO	YES	YES	YES	YES	YES	YES	NO	NO
Liu et al. (2019)	NO	YES	YES	YES	YES	YES	YES	NO	NO
Azizi et al. (2015)	NO	NO (RANDOMLY ASSIGNED, METHODS NOT DESCRIBED)	YES	YES	YES	YES	YES	NO	NO
Raisi et al. (2012)	NO	YES	YES	YES	YES	YES	YES	NO	NO
Carvalho et al. (2018)	NO	YES	YES	YES	YES	YES	YES	NO	NO
Duda et al. (2014)	NO	YES	YES	YES	YES	YES	YES	NO	NO
Haastert-Talini et al. (2013)	NO	YES	YES	YES	YES	YES	YES	NO	NO
Sun et al. (2024)	YES	YES	NO	YES	YES	YES	YES	YES	NO
Zhang et al. (2024)	YES	YES	YES	YES	YES	YES	YES	YES	YES
Jafarisavari et al. (2024)	NO	YES	YES	YES	NO	NO	NO	YES	YES
Xue et al. (2024)	NO	YES	YES	YES	NO	NO	YES	NO	YES
Al-Haideri and Al-Timmemi (2024)	Yes	Yes	No	Yes	Yes	Yes	Yes	No	No
Li et al. (2024)	YES	YES	YES	YES	YES	YES	NO	YES	YES
Zhang et al. (2023)	YES	YES	NO	YES	NO	NO	YES	YES	NO
Qi et al. (2023)	YES	YES	YES	YES	YES	YES	YES	YES	YES
Wang et al. (2023)	YES	YES	YES	YES	YES	YES	YES	YES	YES
Li et al. (2023)	YES	YES	YES	YES	YES	YES	YES	YES	YES

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[1] This table presents the databases searched, specific strategies and terms used, time frame, and total number of results found for studies on chitosan and peripheral nerve injuries in animal models.