{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T19:45:24Z","timestamp":1775072724292,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003086","name":"Basque Government","doi-asserted-by":"publisher","award":["ELKARTEK program (KK-2021\/00040 and KK-2021\/00082)"],"award-info":[{"award-number":["ELKARTEK program (KK-2021\/00040 and KK-2021\/00082)"]}],"id":[{"id":"10.13039\/501100003086","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish State Research Agency (AEI)","award":["PID2019-106099RB-C43\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2019-106099RB-C43\/AEI\/10.13039\/501100011033"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Three-dimensional (3D) printing represents a suitable technology for the development of biomimetic scaffolds for biomedical and tissue engineering applications. However, hydrogel-based inks\u2019 printability remains a challenge due to their restricted print accuracy, mechanical properties, swelling or even cytotoxicity. Chitosan is a natural-derived polysaccharide that has arisen as a promising bioink due to its biodegradability, biocompatibility, sustainability and antibacterial properties, among others, as well as its ability to form hydrogels under the influence of a wide variety of mechanisms (thermal, ionic, pH, covalent, etc.). Its poor solubility at physiological pH, which has traditionally restricted its use, represents, on the contrary, the simplest way to induce chitosan gelation. Accordingly, herein a NaOH strong base was employed as gelling media for the direct 3D printing of chitosan structures. The obtained hydrogels were characterized in terms of morphology, chemical interactions, swelling and mechanical and rheological properties in order to evaluate the influence of the gelling solution\u2019s ionic strength on the hydrogel characteristics. Further, the influence of printing parameters, such as extrusion speed (300, 600 and 800 mm\/min) and pressure (20\u201335 kPa) and the cytocompatibility were also analyzed. In addition, printed gels show an electro-induced motion due to their polycationic nature, which highlights their potential as soft actuators and active scaffolds.<\/jats:p>","DOI":"10.3390\/polym14030650","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T23:42:20Z","timestamp":1644363740000},"page":"650","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["pH-Induced 3D Printable Chitosan Hydrogels for Soft Actuation"],"prefix":"10.3390","volume":"14","author":[{"given":"Sheila","family":"Maiz-Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"BCMaterials (Basque Center for Materials), Applications and Nanostructures, UPV\/EHU Science Park, 48940 Leioa, Spain"},{"name":"Macromolecular Chemistry Group (LABQUIMAC), Department of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country, UPV\/EHU, Barrio Sarriena, s\/n, 48940 Leioa, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0543-4134","authenticated-orcid":false,"given":"Leyre","family":"P\u00e9rez-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"BCMaterials (Basque Center for Materials), Applications and Nanostructures, UPV\/EHU Science Park, 48940 Leioa, Spain"},{"name":"Macromolecular Chemistry Group (LABQUIMAC), Department of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country, UPV\/EHU, Barrio Sarriena, s\/n, 48940 Leioa, Spain"}]},{"given":"Unai","family":"Silv\u00e1n","sequence":"additional","affiliation":[{"name":"BCMaterials (Basque Center for Materials), Applications and Nanostructures, UPV\/EHU Science Park, 48940 Leioa, Spain"},{"name":"Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-4579","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Vilas-Vilela","sequence":"additional","affiliation":[{"name":"BCMaterials (Basque Center for Materials), Applications and Nanostructures, UPV\/EHU Science Park, 48940 Leioa, Spain"},{"name":"Macromolecular Chemistry Group (LABQUIMAC), Department of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country, UPV\/EHU, Barrio Sarriena, s\/n, 48940 Leioa, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6791-7620","authenticated-orcid":false,"given":"Senentxu","family":"Lanceros-M\u00e9ndez","sequence":"additional","affiliation":[{"name":"BCMaterials (Basque Center for Materials), Applications and Nanostructures, UPV\/EHU Science Park, 48940 Leioa, Spain"},{"name":"Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18338","DOI":"10.1021\/acsami.8b04116","article-title":"Fabrication of Multiple-Layered Hydrogel Scaffolds with Elaborate Structure and Good Mechanical Properties via 3D Printing and Ionic Reinforcement","volume":"10","author":"Wang","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1002\/adhm.201500168","article-title":"3D Printing of Scaffolds for Tissue Regeneration Applications","volume":"4","author":"Do","year":"2015","journal-title":"Adv. Healthc. Mater."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.eng.2018.07.021","article-title":"A Review of 3D Printing Technology for Medical Applications","volume":"4","author":"Yan","year":"2018","journal-title":"Engineering"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1002\/ar.1115","article-title":"Injectable gels for tissue engineering","volume":"263","author":"Gutowska","year":"2001","journal-title":"Anat. Rec."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1021\/bm200083n","article-title":"Biopolymer-Based Hydrogels as Scaffolds for Tissue Engineering Applications: A Review","volume":"12","author":"Dubruel","year":"2011","journal-title":"Biomacromolecules"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.addr.2015.11.019","article-title":"ECM and ECM-like materials\u2014Biomaterials for applications in regenerative medicine and cancer therapy","volume":"97","author":"Hinderer","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/nature21001","article-title":"Sustainable polymers from renewable resources","volume":"540","author":"Zhu","year":"2016","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1910606","DOI":"10.1002\/adfm.201910606","article-title":"4D Printing of Hydrogels: A Review","volume":"30","author":"Champeau","year":"2020","journal-title":"Adv. Funct. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40824-018-0122-1","article-title":"Recent trends in bioinks for 3D printing","volume":"22","author":"Gopinathan","year":"2018","journal-title":"Biomater. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Collado-Gonz\u00e1lez, M., Espinosa, Y.G., and Goycoolea, F.M. (2019). Interaction between Chitosan and Mucin: Fundamentals and applications. Biomimetics, 4.","DOI":"10.3390\/biomimetics4020032"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"552","DOI":"10.3390\/polym7030552","article-title":"Chitosan: Gels and interfacial properties","volume":"7","author":"Strand","year":"2015","journal-title":"Polymers"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41598-018-36613-8","article-title":"Study of 3D-printed chitosan scaffold features after different post-printing gelation processes","volume":"9","author":"Bergonzi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_13","first-page":"154","article-title":"Utility of Chitosan for 3D Printing and Bioprinting","volume":"Volume 3","author":"Crini","year":"2019","journal-title":"Sustainable Agriculture Reviews"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"117768","DOI":"10.1016\/j.carbpol.2021.117768","article-title":"Chitosan hydrogels in 3D printing for biomedical applications","volume":"260","author":"Rajabi","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0939-6411(02)00052-8","article-title":"The influence of multivalent phosphate structure on the properties of ionically cross-linked chitosan films for controlled drug release","volume":"54","author":"Shu","year":"2002","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.ijbiomac.2021.08.022","article-title":"3D printable self-healing hyaluronic acid\/chitosan polycomplex hydrogels with drug release capability","volume":"188","author":"Barroso","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13036-015-0001-4","article-title":"Recent advances in 3D printing of biomaterials","volume":"9","author":"Chia","year":"2015","journal-title":"J. Biol. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.actbio.2013.10.035","article-title":"Impact of 3-D printed PLA- and chitosan-based scaffolds on human monocyte\/macrophage responses: Unraveling the effect of 3-D structures on inflammation","volume":"10","author":"Almeida","year":"2014","journal-title":"Acta Biomater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1021\/acsbiomaterials.8b00415","article-title":"Processing and Properties of Chitosan Inks for 3D Printing of Hydrogel Microstructures","volume":"4","author":"Wu","year":"2018","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1021\/acsbiomaterials.8b00804","article-title":"3D Printing of Silk Particle-Reinforced Chitosan Hydrogel Structures and Their Properties","volume":"4","author":"Zhang","year":"2018","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1089\/3dp.2017.0054","article-title":"Polyelectrolyte Soft Actuators: 3D Printed Chitosan and Cast Gelatin","volume":"5","author":"Zolfagharian","year":"2018","journal-title":"3D Print. Addit. Manuf."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jmbbm.2017.12.018","article-title":"Mechanical behaviour of alginate-gelatin hydrogels for 3D bioprinting","volume":"79","author":"Law","year":"2018","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"035020","DOI":"10.1088\/1758-5090\/8\/3\/035020","article-title":"Effect of bioink properties on printability and cell viability for 3D bioplotting of embryonic stem cells","volume":"8","author":"Ouyang","year":"2016","journal-title":"Biofabrication"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1021\/bm0156431","article-title":"Sol-Gel transition temperature of PLGA-g-PEG aqueous solutions","volume":"3","author":"Chung","year":"2002","journal-title":"Biomacromolecules"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mohammed, M.A., Syeda, J.T.M., Wasan, K.M., and Wasan, E.K. (2017). An overview of chitosan nanoparticles and its application in non-parenteral drug delivery. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9040053"},{"key":"ref_27","first-page":"7","article-title":"Chitosan-based inks: 3D printing and bioprinting strategies to improve shape fidelity, mechanical properties, and biocompatibility of 3D scaffolds","volume":"27","year":"2019","journal-title":"Biomec\u00e1nica"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0939-6411(03)00161-9","article-title":"Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications","volume":"57","author":"Berger","year":"2004","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"30071","DOI":"10.1021\/acsami.6b16183","article-title":"Enhanced Release of Molecules upon Ultraviolet (UV) Light Irradiation from Photoresponsive Hydrogels Prepared from Bifunctional Azobenzene and Four-Arm Poly(ethylene glycol)","volume":"10","author":"Rastogi","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.colsurfb.2014.03.002","article-title":"Effects of genipin cross-linking of chitosan hydrogels on cellular adhesion and viability","volume":"117","author":"Gao","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.carbpol.2016.08.007","article-title":"Polyelectrolyte complexes via desalting mixtures of hyaluronic acid and chitosan\u2014Physicochemical study and structural analysis","volume":"154","author":"Sudre","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s10971-006-9007-1","article-title":"Gelation time and degradation rate of chitosan-based injectable hydrogel","volume":"42","author":"Ganji","year":"2007","journal-title":"J. Sol-Gel Sci. Technol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.ijbiomac.2020.12.011","article-title":"3D-printed bioactive and biodegradable hydrogel scaffolds of alginate\/gelatin\/cellulose nanocrystals for tissue engineering","volume":"167","author":"Dutta","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"17162","DOI":"10.1039\/C8NJ03482F","article-title":"The chitosan hydrogels: From structure to function","volume":"42","author":"Fu","year":"2018","journal-title":"New J. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/app.12541","article-title":"Electrical response characterization of chitosan\/polyacrylonitrile hydrogel in NaCl solutions","volume":"90","author":"Kim","year":"2003","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5520","DOI":"10.1016\/j.polymer.2008.09.067","article-title":"Chitosan-based electroactive hydrogel","volume":"49","author":"Shang","year":"2008","journal-title":"Polymer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2000138","DOI":"10.1002\/aisy.202000138","article-title":"Intelligent Polymer-Based Bioinspired Actuators: From Monofunction to Multifunction","volume":"2","author":"Cui","year":"2020","journal-title":"Adv. Intell. Syst."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/14\/3\/650\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:16:27Z","timestamp":1760134587000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/14\/3\/650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,8]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["polym14030650"],"URL":"https:\/\/doi.org\/10.3390\/polym14030650","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,8]]}}}