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Polymers 2018, 10(11), 1202; https://doi.org/10.3390/polym10111202

Injectable and Gellable Chitosan Formulations Filled with Cellulose Nanofibers for Intervertebral Disc Tissue Engineering

1
Institute of Microsystems Engineering IMTEK, Laboratory for Sensors, University of Freiburg, 79110 Freiburg, Germany
2
Freiburg Materials Research Center FMF, University of Freiburg, 79104 Freiburg, Germany
3
Ingénierie des Matériaux Polymères (IMP), CNRS UMR 5223, Université Claude Bernard Lyon 1, Université de Lyon, 69622 Villeurbanne Cedex, France
4
VetAgro Sup, Veterinary School, University of Lyon, 69280 Marcy l’Etoile, France
5
Centre de Recherches sur les Macromolécules Végétales (CERMAV)-CNRS UPR 5301 Université Grenoble-Alpes, 38041 Grenoble, France
6
INSERM U1026 Bioingénierie tissulaire, Université Bordeaux, 33000 Bordeaux, France
7
COPPE/Program of Metallurgical and Materials Engineering, Federal University of Rio de Janeiro, P.O. Box 68505, 21941-972 Rio de Janeiro, Brazil
*
Author to whom correspondence should be addressed.
Received: 5 September 2018 / Revised: 21 October 2018 / Accepted: 22 October 2018 / Published: 27 October 2018
(This article belongs to the Special Issue Chitin and Chitosan: Properties and Applications)
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Abstract

The development of non-cellularized injectable suspensions of viscous chitosan (CHI) solutions (1.7–3.3% (w/w)), filled with cellulose nanofibers (CNF) (0.02–0.6% (w/w)) of the type nanofibrillated cellulose, was proposed for viscosupplementation of the intervertebral disc nucleus pulposus tissue. The achievement of CNF/CHI formulations which can gel in situ at the disc injection site constitutes a minimally-invasive approach to restore damaged/degenerated discs. We studied physico-chemical aspects of the sol and gel states of the CNF/CHI formulations, including the rheological behavior in relation to injectability (sol state) and fiber mechanical reinforcement (gel state). CNF-CHI interactions could be evidenced by a double flow behavior due to the relaxation of the CHI polymer chains and those interacting with the CNFs. At high shear rates resembling the injection conditions with needles commonly used in surgical treatments, both the reference CHI viscous solutions and those filled with CNFs exhibited similar rheological behavior. The neutralization of the flowing and weakly acidic CNF/CHI suspensions yielded composite hydrogels in which the nanofibers reinforced the CHI matrix. We performed evaluations in relation to the biomedical application, such as the effect of the intradiscal injection of the CNF/CHI formulation in pig and rabbit spine models on disc biomechanics. We showed that the injectable formulations became hydrogels in situ after intradiscal gelation, due to CHI neutralization occurring in contact with the body fluids. No leakage of the injectate through the injection canal was observed and the gelled formulation restored the disc height and loss of mechanical properties, which is commonly related to disc degeneration. View Full-Text
Keywords: chitosan; cellulose nanofibers; composite hydrogel; injectable biomaterial; rheological behavior; intervertebral disc; tissue engineering chitosan; cellulose nanofibers; composite hydrogel; injectable biomaterial; rheological behavior; intervertebral disc; tissue engineering
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Doench, I.; Torres-Ramos, M.E.W.; Montembault, A.; Nunes de Oliveira, P.; Halimi, C.; Viguier, E.; Heux, L.; Siadous, R.; Thiré, R.M.S.M.; Osorio-Madrazo, A. Injectable and Gellable Chitosan Formulations Filled with Cellulose Nanofibers for Intervertebral Disc Tissue Engineering. Polymers 2018, 10, 1202.

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