Thermogelling chitosan lactate hydrogel improves functional recovery after a C2 spinal cord hemisection in rat.
The present study was designed to provide an appropriate micro-environment for regenerating axotomized neurons and proliferating/migrating cells. Because of its intrinsic permissive properties, biocompatibility and biodegradability, we chose to evaluate the therapeutic effectiveness of a chitosan-based biopolymer. The biomaterial toxicity was measured through in vitro test based on fibroblast cell survival on thermogelling chitosan lactate hydrogel substrate and then polymer was implanted into a C2 hemisection of the rat spinal cord. Animals were randomized into three experimental groups (Control, Lesion and Lesion + Hydrogel) and functional tests (ladder walking and forelimb grip strength tests, respiratory assessment by whole-body plethysmography measurements) were used, once a week during 10 weeks, to evaluate post-traumatic recoveries. Then, electrophysiological examinations (reflexivity of the sub-lesional region, ventilatory adjustments to muscle fatigue known to elicit the muscle metaboreflex and phrenic nerve recordings during normoxia and temporary hypoxia) were performed. In vitro results indicated that the chitosan matrix is a non-toxic biomaterial that allowed fibroblast survival. Furthermore, implanted animals showed improvements of their ladder walking scores from the 4th week post-implantation. Finally, electrophysiological recordings indicated that animals receiving the chitosan matrix exhibited recovery of the H-reflex rate sensitive depression, the ventilatory response to repetitive muscle stimulation and an increase of the phrenic nerve activity to asphyxia compared to lesioned and nonimplanted animals. This study indicates that hydrogel based on chitosan constitute a promising therapeutic approach to repair damaged spinal cord or may be used as an adjuvant with other treatments to enhance functional recovery after a central nervous system damage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2004-2019, 2017.
Faculty of Process and Environmental Engineering, Department of Chemical Engineering, Lodz University of Technology, Wolczanska 175 Street, Lodz, 90-924, Poland.
Katarzyna
K
Nawrotek
Aix-Marseille Université (AMU) and Centre National de la Recherche Scientifique (CNRS), Institut des Sciences du Mouvement (UMR 7287), Equipe « Plasticité des Systèmes Nerveux et Musculaire », Parc Scientifique et Technologique de Luminy, CC910-163, Avenue de Luminy, F-13288, Marseille Cedex 09, France.
Tanguy
T
Marqueste
Faculty of Process and Environmental Engineering, Department of Chemical Engineering, Lodz University of Technology, Wolczanska 175 Street, Lodz, 90-924, Poland.
Zofia
Z
Modrzejewska
Faculty of Process and Environmental Engineering, Department of Chemical Engineering, Lodz University of Technology, Wolczanska 175 Street, Lodz, 90-924, Poland.
Roman
R
Zarzycki
Department of Experimental Surgery and Biomaterials Research, Wroclaw Medical University, Medico-Dental Faculty, Krakowska 26 Street, Wroclaw, Poland, 50-425.
Agnieszka
A
Rusak
Aix-Marseille Université (AMU) and Centre National de la Recherche Scientifique (CNRS), Institut des Sciences du Mouvement (UMR 7287), Equipe « Plasticité des Systèmes Nerveux et Musculaire », Parc Scientifique et Technologique de Luminy, CC910-163, Avenue de Luminy, F-13288, Marseille Cedex 09, France.
Patrick
P
Decherchi
D000818:Animals; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy
D020100:Hydrogels; D019344:Lactic Acid; D048271:Chitosan
biomaterial; monosynaptic Ia afferent reflex; motoneuron recruitment; phrenic nerve; spasticity