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

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.

SUBMITTER: Doench I

PROVIDER: S-EPMC6290636 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Doench Ingo I Torres-Ramos Maria E W MEW Montembault Alexandra A Nunes de Oliveira Paula P Halimi Celia C Viguier Eric E Heux Laurent L Siadous Robin R Thiré Rossana M S M RMSM Osorio-Madrazo Anayancy A

Polymers 20181027 11

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 s ...[more]

PMID: 30961127

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Project description:Extremely high mechanical performance spun bionanocomposite fibers of chitosan (CHI), and cellulose nanofibers (CNFs) were successfully achieved by gel spinning of CHI aqueous viscous formulations filled with CNFs. The microstructural characterization of the fibers by X-ray diffraction revealed the crystallization of the CHI polymer chains into anhydrous chitosan allomorph. The spinning process combining acidic-basic-neutralization-stretching-drying steps allowed obtaining CHI/CNF composite fibers of high crystallinity, with enhanced effect at incorporating the CNFs. Chitosan crystallization seems to be promoted by the presence of cellulose nanofibers, serving as nucleation sites for the growing of CHI crystals. Moreover, the preferential orientation of both CNFs and CHI crystals along the spun fiber direction was revealed in the two-dimensional X-ray diffraction patterns. By increasing the CNF amount up to the optimum concentration of 0.4 wt % in the viscous CHI/CNF collodion, Young's modulus of the spun fibers significantly increased up to 8 GPa. Similarly, the stress at break and the yield stress drastically increased from 115 to 163 MPa, and from 67 to 119 MPa, respectively, by adding only 0.4 wt % of CNFs into a collodion solution containing 4 wt % of chitosan. The toughness of the CHI-based fibers thereby increased from 5 to 9 MJ.m-3. For higher CNFs contents like 0.5 wt %, the high mechanical performance of the CHI/CNF composite fibers was still observed, but with a slight worsening of the mechanical parameters, which may be related to a minor disruption of the CHI matrix hydrogel network constituting the collodion and gel fiber, as precursor state for the dry fiber formation. Finally, the rheological behavior observed for the different CHI/CNF viscous collodions and the obtained structural, thermal and mechanical properties results revealed an optimum matrix/filler compatibility and interface when adding 0.4 wt % of nanofibrillated cellulose (CNF) into 4 wt % CHI formulations, yielding functional bionanocomposite fibers of outstanding mechanical properties.

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Dataset Information

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

Publications

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

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