{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:40:58Z","timestamp":1792723258933,"version":"4.5.0"},"reference-count":74,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,10,27]],"date-time":"2018-10-27T00:00:00Z","timestamp":1540598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>The development of non-cellularized injectable suspensions of viscous chitosan (CHI) solutions (1.7\u20133.3% (w\/w)), filled with cellulose nanofibers (CNF) (0.02\u20130.6% (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.<\/jats:p>","DOI":"10.3390\/polym10111202","type":"journal-article","created":{"date-parts":[[2018,10,29]],"date-time":"2018-10-29T11:10:41Z","timestamp":1540811441000},"page":"1202","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Injectable and Gellable Chitosan Formulations Filled with Cellulose Nanofibers for Intervertebral Disc Tissue Engineering"],"prefix":"10.3390","volume":"10","author":[{"given":"Ingo","family":"Doench","sequence":"first","affiliation":[{"name":"Institute of Microsystems Engineering IMTEK, Laboratory for Sensors, University of Freiburg, 79110 Freiburg, Germany"},{"name":"Freiburg Materials Research Center FMF, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Torres-Ramos","sequence":"additional","affiliation":[{"name":"Institute of Microsystems Engineering IMTEK, Laboratory for Sensors, University of Freiburg, 79110 Freiburg, Germany"},{"name":"Freiburg Materials Research Center FMF, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1820-5832","authenticated-orcid":false,"given":"Alexandra","family":"Montembault","sequence":"additional","affiliation":[{"name":"Ing\u00e9nierie des Mat\u00e9riaux Polym\u00e8res (IMP), CNRS UMR 5223, Universit\u00e9 Claude Bernard Lyon 1, Universit\u00e9 de Lyon, 69622 Villeurbanne Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Nunes de Oliveira","sequence":"additional","affiliation":[{"name":"Ing\u00e9nierie des Mat\u00e9riaux Polym\u00e8res (IMP), CNRS UMR 5223, Universit\u00e9 Claude Bernard Lyon 1, Universit\u00e9 de Lyon, 69622 Villeurbanne Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Halimi","sequence":"additional","affiliation":[{"name":"Ing\u00e9nierie des Mat\u00e9riaux Polym\u00e8res (IMP), CNRS UMR 5223, Universit\u00e9 Claude Bernard Lyon 1, Universit\u00e9 de Lyon, 69622 Villeurbanne Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3137-5457","authenticated-orcid":false,"given":"Eric","family":"Viguier","sequence":"additional","affiliation":[{"name":"VetAgro Sup, Veterinary School, University of Lyon, 69280 Marcy l\u2019Etoile, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Heux","sequence":"additional","affiliation":[{"name":"Centre de Recherches sur les Macromol\u00e9cules V\u00e9g\u00e9tales (CERMAV)-CNRS UPR 5301 Universit\u00e9 Grenoble-Alpes, 38041 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Siadous","sequence":"additional","affiliation":[{"name":"INSERM U1026 Bioing\u00e9nierie tissulaire, Universit\u00e9 Bordeaux, 33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0026-5431","authenticated-orcid":false,"given":"Rossana","family":"Thir\u00e9","sequence":"additional","affiliation":[{"name":"COPPE\/Program of Metallurgical and Materials Engineering, Federal University of Rio de Janeiro, P.O. Box 68505, 21941-972 Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anayancy","family":"Osorio-Madrazo","sequence":"additional","affiliation":[{"name":"Institute of Microsystems Engineering IMTEK, Laboratory for Sensors, University of Freiburg, 79110 Freiburg, Germany"},{"name":"Freiburg Materials Research Center FMF, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sharifi, S., Bulstra, S.K., Grijpma, D.W., and Kuijer, R. (2015). Treatment of the degenerated intervertebral disc; closure, repair and regeneration of the annulus fibrosus. J. Tissue Eng. Regen. Med.","DOI":"10.1002\/term.1866"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E668","DOI":"10.1097\/BRS.0b013e318241e5de","article-title":"The burden of chronic low back pain: Clinical comorbidities, treatment patterns, and health care costs in usual care settings","volume":"37","author":"Gore","year":"2012","journal-title":"Spine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1097\/00024720-200308000-00009","article-title":"Complications of artificial disc replacement: A report of 27 patients with the SB Charit\u00e9 disc","volume":"16","author":"Oner","year":"2003","journal-title":"J. Spinal Disord. Tech."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1097\/01.brs.0000146499.97948.52","article-title":"Nutrition of the intervertebral disc","volume":"29","author":"Urban","year":"2004","journal-title":"Spine"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Chan, S.C.W., and Gantenbein-Ritter, B. (2012). Intervertebral disc regeneration or repair with biomaterials and stem cell therapy\u2014Feasible or fiction?. Swiss Med. Wkly.","DOI":"10.4414\/smw.2012.13598"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.msec.2011.10.011","article-title":"Intervertebral disc (IVD): Structure, degeneration, repair and regeneration","volume":"32","author":"Whatley","year":"2012","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yoganandan, N., Pintar, F.A., Larson, S.J., and Sances, A.J. (1998). Biomechanical models of the cervical spine. Frontiers in Head and Neck Trauma: Clinical and Biomechanical, IOS Press.","DOI":"10.1037\/e454782006-001"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.1097\/00007632-199912010-00008","article-title":"In Vivo Intradiscal Pressure Measurement in Healthy Individuals and in Patients With Ongoing Back Problems","volume":"24","author":"Sato","year":"1999","journal-title":"Spine"},{"key":"ref_9","first-page":"42","article-title":"Relationship Between Structure and Mechanical Function of the Tissues of the Intervertebral Joint","volume":"40","author":"Hukins","year":"2000","journal-title":"Am. Zool."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1302\/0301-620X.78B6.0780965","article-title":"\u2018Stress\u2019 distributions inside intervertebral discs. The effects of age and degeneration","volume":"78","author":"Adams","year":"1996","journal-title":"J. Bone Jt. Surg. Br. Vol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.biomaterials.2005.06.037","article-title":"The potential of chitosan-based gels containing intervertebral disc cells for nucleus pulposus supplementation","volume":"27","author":"Roughley","year":"2006","journal-title":"Biomaterials"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1002\/jbm.a.32191","article-title":"Characterization of photocrosslinked alginate hydrogels for nucleus pulposus cell encapsulation","volume":"91A","author":"Chou","year":"2009","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.carbpol.2015.07.071","article-title":"Macro-hydrogels versus nanoparticles by the controlled assembly of polysaccharides","volume":"134","author":"Costalat","year":"2015","journal-title":"Carbohydr. Polym."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8556","DOI":"10.1016\/j.biomaterials.2010.07.100","article-title":"Human macrophage activation triggered by chitotriosidase-mediated chitin and chitosan degradation","volume":"31","author":"Gorzelanny","year":"2010","journal-title":"Biomaterials"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/(SICI)1097-4636(199701)34:1<21::AID-JBM4>3.0.CO;2-P","article-title":"Use of chitosan as a biomaterial: Studies on its safety and hemostatic potential","volume":"34","author":"Rao","year":"1997","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0142-9612(00)00183-6","article-title":"Influence of the degree of acetylation on some biological properties of chitosan films","volume":"22","author":"Chatelet","year":"2001","journal-title":"Biomaterials"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/j.1365-2184.2011.00788.x","article-title":"Chitosan enhances mineralization during osteoblast differentiation of human bone marrow-derived mesenchymal stem cells, by upregulating the associated genes","volume":"44","author":"Mathews","year":"2011","journal-title":"Cell Prolif."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1038\/s41598-017-02962-z","article-title":"Injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for abdominal tissue regeneration","volume":"7","author":"Deng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5354","DOI":"10.1016\/j.biomaterials.2011.04.012","article-title":"Multi-membrane chitosan hydrogels as chondrocytic cell bioreactors","volume":"32","author":"Ladet","year":"2011","journal-title":"Biomaterials"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.biochi.2006.03.002","article-title":"A material decoy of biological media based on chitosan physical hydrogels: Application to cartilage tissue engineering","volume":"88","author":"Montembault","year":"2006","journal-title":"Biochimie"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/nature06619","article-title":"Multi-membrane hydrogels","volume":"452","author":"Ladet","year":"2008","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1021\/bm201764y","article-title":"Reorientation of cellulose nanowhiskers in agarose hydrogels under tensile loading","volume":"13","author":"Eder","year":"2012","journal-title":"Biomacromolecules"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.carbpol.2015.05.011","article-title":"Fine microstructure of processed chitosan nanofibril networks preserving directional packing and high molecular weight","volume":"131","author":"David","year":"2015","journal-title":"Carbohydr. Polym."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1016\/j.carbpol.2010.10.035","article-title":"Highly crystalline chitosan produced by multi-steps acid hydrolysis in the solid-state","volume":"83","author":"David","year":"2011","journal-title":"Carbohydr. Polym."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dufresne, A., Thomas, S., and Pothen, L.A. (2013). Morphological and Thermal Investigations of Cellulosic Bionanocomposites. Biopolymer Nanocomposites, John Wiley & Sons, Inc.","DOI":"10.1002\/9781118609958"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Barhoum, A., Bechelany, M., and Makhlouf, A. (2018). Native Crystalline Polysaccharide Nanofibers: Processing and Properties. Handbook of Nanofibers, Springer International Publishing.","DOI":"10.1007\/978-3-319-53655-2"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1007\/s10570-013-9942-2","article-title":"Preparation of cellulose I nanowhiskers with a mildly acidic aqueous ionic liquid: Reaction efficiency and whiskers attributes","volume":"20","author":"Mao","year":"2013","journal-title":"Cellulose"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6365","DOI":"10.1021\/ma00122a053","article-title":"Polymer nanocomposites reinforced by cellulose whiskers","volume":"28","author":"Favier","year":"1995","journal-title":"Macromolecules"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5438","DOI":"10.1002\/anie.201001273","article-title":"Nanocelluloses: A New Family of Nature-Based Materials","volume":"50","author":"Klemm","year":"2011","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1021\/bm049291k","article-title":"Elastic Modulus and Stress-Transfer Properties of Tunicate Cellulose Whiskers","volume":"6","author":"Davies","year":"2005","journal-title":"Biomacromolecules"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Choo, K., Ching, Y., Chuah, C., Julai, S., and Liou, N.-S. (2016). Preparation and Characterization of Polyvinyl Alcohol-Chitosan Composite Films Reinforced with Cellulose Nanofiber. Materials, 9.","DOI":"10.3390\/ma9080644"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.ijbiomac.2016.09.010","article-title":"Evaluation of mixing efficiency in elaborating of chitosan\/cellulose nanocomposite via statistical analyses","volume":"93","author":"Ghazanfari","year":"2016","journal-title":"Int. J. Boil. Macromol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1021\/bm9011985","article-title":"Biobased Nanocomposites from Layer-by-Layer Assembly of Cellulose Nanowhiskers with Chitosan","volume":"11","author":"Donnici","year":"2010","journal-title":"Biomacromolecules"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"42004","DOI":"10.1002\/app.42004","article-title":"Bio-nanocomposite films based on cellulose nanocrystals filled polyvinyl alcohol\/chitosan polymer blend","volume":"132","author":"Abdelouahdi","year":"2015","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.compscitech.2015.05.004","article-title":"Preparation and characterization of nanocomposites of polyvinyl alcohol\/cellulose nanowhiskers\/chitosan","volume":"115","author":"Li","year":"2015","journal-title":"Compos. Sci. Technol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.carbpol.2016.05.028","article-title":"A review on chitosan-cellulose blends and nanocellulose reinforced chitosan biocomposites: Properties and their applications","volume":"150","author":"Khalil","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.carbpol.2015.07.007","article-title":"Effects of processing on the properties of chitosan\/cellulose nanocrystal films","volume":"133","author":"Celebi","year":"2015","journal-title":"Carbohydr. Polym."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.carbpol.2016.07.042","article-title":"Chitosan-chitin nanocrystal composite scaffolds for tissue engineering","volume":"152","author":"Liu","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"255","DOI":"10.3109\/17435391003628713","article-title":"An ecotoxicological characterization of nanocrystalline cellulose (NCC)","volume":"4","author":"Kovacs","year":"2010","journal-title":"Nanotoxicology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1163\/092050611X581516","article-title":"Bacterial Cellulose: Long-Term Biocompatibility Studies","volume":"23","author":"Moreira","year":"2012","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_41","unstructured":"Pitk\u00e4nen, M., Honkalampi, U., von Wright, A., Sneck, A., Hentze, H-P., Siev\u00e4nen, J., Hiltunen, J., and Hell\u00e9n, E.K.O. (2010). Nanofibrillar Cellulose. In Vitro Study of Cytotoxic and Genotoxic Properties, TAPPI."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1021\/bm101131b","article-title":"Biocomposite Hydrogels with Carboxymethylated, Nanofibrillated Cellulose Powder for Replacement of the Nucleus Pulposus","volume":"12","author":"Eyholzer","year":"2011","journal-title":"Biomacromolecules"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1016\/j.actbio.2011.05.029","article-title":"Nanofibrillated cellulose composite hydrogel for the replacement of the nucleus pulposus","volume":"7","author":"Borges","year":"2011","journal-title":"Acta Biomater."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1021\/acs.chemmater.7b00531","article-title":"Review of Hydrogels and Aerogels Containing Nanocellulose","volume":"29","author":"Hoare","year":"2017","journal-title":"Chem. Mater."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.carbpol.2017.10.032","article-title":"In vitro and in vivo acute response towards injectable thermosensitive chitosan\/TEMPO-oxidized cellulose nanofiber hydrogel","volume":"180","author":"Nguyen","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1021\/acs.biomac.6b00075","article-title":"Chitosan Hydrogels for the Regeneration of Infarcted Myocardium: Preparation, Physicochemical Characterization, and Biological Evaluation","volume":"17","author":"Fiamingo","year":"2016","journal-title":"Biomacromolecules"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1021\/bm061215p","article-title":"Enzymatic Hydrolysis Combined with Mechanical Shearing and High-Pressure Homogenization for Nanoscale Cellulose Fibrils and Strong Gels","volume":"8","author":"Ankerfors","year":"2007","journal-title":"Biomacromolecules"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/0095-8522(65)90022-X","article-title":"Rheology of non-Newtonian fluids: A new flow equation for pseudoplastic systems","volume":"20","author":"Cross","year":"1965","journal-title":"J. Colloid Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.foodhyd.2010.03.009","article-title":"Flow behaviour, linear viscoelasticity and surface properties of chitosan aqueous solutions","volume":"24","author":"Calero","year":"2010","journal-title":"Food Hydrocoll."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Halimi, C., Montembault, A., Guerry, A., Delair, T., Viguier, E., Fulchiron, R., and David, L. (2015, January 25\u201329). Chitosan solutions as injectable systems for dermal filler applications: Rheological characterization and biological evidence. Proceedings of the 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Milano, Italy.","DOI":"10.1109\/EMBC.2015.7318923"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1119\/1.16328","article-title":"Generalization of the Hagen-Poiseuille velocity profile to non-Newtonian fluids and measurement of their viscosity","volume":"58","author":"Eu","year":"1990","journal-title":"Am. J. Phys."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1021\/i160016a011","article-title":"Power-Law Flow through a Packed Tube","volume":"4","author":"Christopher","year":"1965","journal-title":"Ind. Eng. Chem. Fundam."},{"key":"ref_53","unstructured":"Schramm, G. (1998). A Practical Approach to Rheology and Rheometry, Gebrueder HAAKE GmbH."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1002\/app.38389","article-title":"Influence of particle size and fluid fraction on rheological and extrusion properties of crosslinked hyaluronic acid hydrogel dispersions","volume":"128","author":"Martins","year":"2013","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_55","unstructured":"ISO10993-5 (1992). Biological Evaluation of Medical Devices. Test for Cytotoxicity: In Vitro Methods, ISO."},{"key":"ref_56","unstructured":"AFNOR6NF EN 30993-5 (1994). Evaluation Biologique des Dispositifs M\u00e9dicaux. Partie 5: Essais Concernant la Cytotoxicit\u00e9: M\u00e9thodes In Vitro, ISO 10993-10."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0022-1759(83)90277-6","article-title":"Automated colorimetric assay for T cell cytotoxicity","volume":"58","author":"Parish","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1177\/0023677214558103","article-title":"Coil optimization for low-field MRI: A dedicated process for small animal preclinical studies","volume":"49","author":"Feuillet","year":"2015","journal-title":"Lab. Anim."},{"key":"ref_60","unstructured":"Halimi, C., David, L., Viguier, E., Delair, T., and Montembault, A. (2017). Chitosan Aqueous Solution for Injection for the Prevention or the Treatment of Intervertebral Disc Degeneration. (FR3039402B1), France Patent."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1016\/j.biomaterials.2004.06.029","article-title":"Rheometric study of the gelation of chitosan in a hydroalcoholic medium","volume":"26","author":"Montembault","year":"2005","journal-title":"Biomaterials"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1021\/bm049593m","article-title":"Rheometric Study of the Gelation of Chitosan in Aqueous Solution without Cross-Linking Agent","volume":"6","author":"Montembault","year":"2005","journal-title":"Biomacromolecules"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1745-4603.2004.tb00822.x","article-title":"Steady-Shear Rheology of Concentrated Chitosan Solutions","volume":"35","author":"Martinez","year":"2004","journal-title":"J. Texture Stud."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.carbpol.2013.04.070","article-title":"Spinning of hydroalcoholic chitosan solutions","volume":"98","author":"Desorme","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_65","first-page":"1","article-title":"Flow behavior of a cationic biopolymer: Chitosan","volume":"13","author":"Rha","year":"1985","journal-title":"Polym. Bull."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1039\/C6CS00895J","article-title":"Current characterization methods for cellulose nanomaterials","volume":"47","author":"Foster","year":"2018","journal-title":"Chem. Soc. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.carbpol.2014.08.047","article-title":"Basic effects of pulp refining on fiber properties\u2014A review","volume":"115","author":"Gharehkhani","year":"2015","journal-title":"Carbohydr. Polym."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3725","DOI":"10.1007\/s10570-017-1401-z","article-title":"Quantification of a tightly adsorbed monolayer of xylan on cellulose surface","volume":"24","author":"Ogawa","year":"2017","journal-title":"Cellulose"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1021\/acs.biomac.5b00145","article-title":"Water-Resistant, Transparent Hybrid Nanopaper by Physical Cross-Linking with Chitosan","volume":"16","author":"Toivonen","year":"2015","journal-title":"Biomacromolecules"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1021\/acs.biomac.5b00539","article-title":"Influence of Flexibility and Dimensions of Nanocelluloses on the Flow Properties of Their Aqueous Dispersions","volume":"16","author":"Tanaka","year":"2015","journal-title":"Biomacromolecules"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1007\/s00586-012-2291-2","article-title":"Injection of a polymerized hyaluronic acid\/collagen hydrogel matrix in an in vivo porcine disc degeneration model","volume":"21","author":"Omlor","year":"2012","journal-title":"Eur. Spine J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1007\/s10856-007-3013-x","article-title":"The controlling biodegradation of chitosan fibers by N-acetylation in vitro and in vivo","volume":"18","author":"Yang","year":"2007","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1017\/S1462399410001481","article-title":"The molecular mediators of type 2 epithelial to mesenchymal transition (EMT) and their role in renal pathophysiology","volume":"12","author":"Burns","year":"2010","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1089\/ten.tea.2014.0174","article-title":"Dose-Dependent Response of Tissue-Engineered Intervertebral Discs to Dynamic Unconfined Compressive Loading","volume":"21","year":"2015","journal-title":"Tissue Eng. Part A"}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/10\/11\/1202\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:26:34Z","timestamp":1760196394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/10\/11\/1202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,27]]},"references-count":74,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2018,11]]}},"alternative-id":["polym10111202"],"URL":"https:\/\/doi.org\/10.3390\/polym10111202","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,27]]}}}