{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T01:15:24Z","timestamp":1771722924991,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese government, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["PTDC\/BTM-SAL\/29335\/2017"],"award-info":[{"award-number":["PTDC\/BTM-SAL\/29335\/2017"]}]},{"name":"Portuguese government, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["UIDB\/04138\/2020"],"award-info":[{"award-number":["UIDB\/04138\/2020"]}]},{"name":"Portuguese government, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["UIDP\/04138\/2020"],"award-info":[{"award-number":["UIDP\/04138\/2020"]}]},{"name":"Portuguese government, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["IPL\/2022\/3DWounDres_ESELx"],"award-info":[{"award-number":["IPL\/2022\/3DWounDres_ESELx"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chitosan is an interesting polymer to produce hydrogels suitable for the 3D printing of customized drug delivery systems. This study aimed at the achievement of chitosan-based scaffolds suitable for the incorporation of active components in the matrix or loaded into the pores. Several scaffolds were printed using different chitosan-based hydrogels. To understand which parameters would have a greater impact on printability, an optimization study was conducted. The scaffolds with the highest printability were obtained with a chitosan hydrogel at 2.5 wt%, a flow speed of 0.15 mm\/s and a layer height of 0.41 mm. To improve the chitosan hydrogel printability, starch was added, and a design of experiments with three factors and two responses was carried out to find out the optimal starch supplementation. It was possible to conclude that the addition of starch (13 wt%) to the chitosan hydrogel improved the structural characteristics of the chitosan-based scaffolds. These scaffolds showed potential to be tested in the future as drug-delivery systems.<\/jats:p>","DOI":"10.3390\/ijms24020973","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T03:12:15Z","timestamp":1672888335000},"page":"973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Improving Chitosan Hydrogels Printability: A Comprehensive Study on Printing Scaffolds for Customized Drug Delivery"],"prefix":"10.3390","volume":"24","author":[{"given":"Sara","family":"Cardoso","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Avenida Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3449-2571","authenticated-orcid":false,"given":"Francisco","family":"Narciso","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Avenida Prof. Gama Pinto, 1649-003 Lisboa, Portugal"},{"name":"Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal"}]},{"given":"Nuno","family":"Monge","sequence":"additional","affiliation":[{"name":"Centro Interdisciplinar de Estudos Educacionais (CIED), Escola Superior de Educa\u00e7\u00e3o de Lisboa, Instituto Polit\u00e9cnico de Lisboa, Campus de Benfica do IPL, 1549-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-5892","authenticated-orcid":false,"given":"Ana","family":"Bettencourt","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Avenida Prof. Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7110-6393","authenticated-orcid":false,"given":"Isabel A. 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Technol."},{"key":"ref_4","first-page":"704","article-title":"Medical Applications for 3D Printing: Current and Projected Uses","volume":"39","author":"Ventola","year":"2014","journal-title":"Pharm. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S1369-7021(04)00233-0","article-title":"Scaffolds for tissue fabrication","volume":"7","author":"Ma","year":"2004","journal-title":"Mater. Today"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s13346-022-01191-w","article-title":"Management of bone diseases: Looking at scaffold-based strategies for drug delivery","volume":"13","author":"Bordone","year":"2022","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Malekpour, A., and Chen, X. (2022). Printability and Cell Viability in Extrusion-Based Bioprinting from Experimental, Computational, and Machine Learning Views. J. Funct. Biomater., 13.","DOI":"10.3390\/jfb13020040"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1016\/j.cclet.2021.03.073","article-title":"3D printing hydrogels for actuators: A review","volume":"32","author":"Zhang","year":"2021","journal-title":"Chin. Chem. Lett."},{"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","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_11","doi-asserted-by":"crossref","first-page":"117433","DOI":"10.1016\/j.carbpol.2020.117433","article-title":"Exploring the potential of chitosan-based particles as delivery-carriers for promising antimicrobial glycolipid biosurfactants","volume":"254","author":"Bettencourt","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3390\/md13031519","article-title":"Chitin and chitosan as direct compression excipients in pharmaceutical applications","volume":"13","author":"Badwan","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.ijbiomac.2017.07.087","article-title":"Chitosan as a bioactive polymer: Processing, properties and applications","volume":"105","author":"Muxika","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kravanja, G., Primo\u017ei\u010d, M., Knez, \u017d., and Leitgeb, M. (2019). Chitosan-Based (Nano)Materials for Novel Biomedical Applications. Molecules, 24.","DOI":"10.3390\/molecules24101960"},{"key":"ref_16","first-page":"1","article-title":"An Overview on Materials and 56 Techniques in 3D Bioprinting Toward Biomedical Application","volume":"2","author":"Vanaei","year":"2021","journal-title":"Eng. Regen."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jobab.2021.04.002","article-title":"New Ulva lactuca Algae Based Chitosan Bio-composites for Bioremediation of Cd(II) Ions","volume":"6","author":"Saad","year":"2021","journal-title":"J. Bioresour. Bioprod."},{"key":"ref_18","first-page":"2214","article-title":"Development of cranberry extract films for the enhancement of food packaging antimicrobial properties","volume":"28","author":"Severo","year":"2021","journal-title":"Food Packag. Shelf Life"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Chatterjee, R., Maity, M., Hasnain, M.S., and Nayak, A.K. (2022). Chitosan: Source, Chemistry, and Properties, Elvesier. Chapter 1.","DOI":"10.1016\/B978-0-12-819336-5.00001-7"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0939-6411(03)00160-7","article-title":"Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications","volume":"57","author":"Berger","year":"2004","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mora-Boza1, A., W\u0142odarczyk-Biegun, M.K., del Campo, A., V\u00e1zquez-Lasa, B., and San Rom\u00e1n, J. (2019). Chitosan-based inks: 3D printing and bioprinting strategies to improve shape fidelity, mechanical properties, and biocompatibility of 3D scaffolds. Biomec\u00e1nica, 27, 7\u201316.","DOI":"10.5821\/sibb.27.1.9199"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10856-019-6318-7","article-title":"Overview of natural hydrogels for regenerative medicine applications","volume":"30","author":"Catoira","year":"2019","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yang, W., Tu, A., Ma, Y., Li, Z., Xu, J., Lin, M., Zhang, K., Jing, L., Fu, C., and Jiao, Y. (2021). Chitosan and Whey Protein Bio-Inks for 3D and 4D Printing Applications with Particular Focus on Food Industry. Molecules, 27.","DOI":"10.3390\/molecules27010173"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1211\/0022357011776441","article-title":"Chitosan: Some pharmaceutical and biological aspects\u2014An update","volume":"53","author":"Singla","year":"2001","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100737","DOI":"10.1016\/j.mtla.2020.100737","article-title":"Optimization of starch- and chitosan-based bio-inks for 3D bioprinting of scaffolds for neural cell growth","volume":"12","author":"Butler","year":"2020","journal-title":"Materialia"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lazaridou, M., Bikiaris, D.N., and Lamprou, D.A. (2022). 3D Bioprinted Chitosan-Based Hydrogel Scaffolds in Tissue Engineering and Localised Drug Delivery. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14091978"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Liu, Q., Li, Q., Xu, S., Zheng, Q., and Cao, X. (2018). Preparation and Properties of 3D Printed Alginate\u207bChitosan Polyion Complex Hydrogels for Tissue Engineering. Polymers, 10.","DOI":"10.3390\/polym10060664"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Michailidou, G., Terzopoulou, Z., Kehagia, A., Michopoulou, A., and Bikiaris, D.N. (2021). Preliminary Evaluation of 3D Printed Chitosan\/Pectin Constructs for Biomedical Applications. Mar. Drugs, 19.","DOI":"10.3390\/md19010036"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"111963","DOI":"10.1016\/j.msec.2021.111963","article-title":"Low-temperature 3D printing of collagen and chitosan composite for tissue engineering","volume":"123","author":"Suo","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jfoodeng.2018.09.011","article-title":"Effect of rheological properties of potato, rice and corn starches on their hot-extrusion 3D printing behaviors","volume":"244","author":"Chen","year":"2019","journal-title":"J. Food. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19508","DOI":"10.1039\/D1RA03410C","article-title":"3D printed chitosan\/polycaprolactone scaffold for lung tissue engineering: Hope to be useful for COVID-19 studies","volume":"11","author":"Rezaei","year":"2021","journal-title":"RSC Adv."},{"key":"ref_32","first-page":"270","article-title":"Nozzle Problem Analysis and Optimization of FDM 3D Printer","volume":"Volume 75","author":"Li","year":"2017","journal-title":"Proceedings of the 7th International Conference on Mechatronics, Computer and Education Informationization (MCEI 2017)"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"102808","DOI":"10.1016\/j.ifset.2021.102808","article-title":"Designing and utilizing 3D printed chitosan\/halloysite nanotubes\/tea polyphenol composites to maintain the quality of fresh blueberries","volume":"74","author":"Liu","year":"2021","journal-title":"Innov. Food Sci. Emerg. Technol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mora-Casta\u00f1o, G., Mill\u00e1n-Jim\u00e9nez, M., Linares, V., and Caraballo, I. (2022). Assessment of the Extrusion Process and Printability of Suspension-Type Drug-Loaded AffinisolTM Filaments for 3D Printing. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14040871"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100149","DOI":"10.1016\/j.sintl.2021.100149","article-title":"Analyzing the Impact of Print Parameters on Dimensional Variation of ABS specimens printed using Fused Deposition Modelling (FDM)","volume":"3","author":"Agarwal","year":"2022","journal-title":"Sens. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jfoodeng.2017.05.015","article-title":"Application of 3D printing for customized food. A case on the development of a fruit-based snack for children","volume":"220","author":"Derossi","year":"2018","journal-title":"J. Food Eng."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Pahlevanzadeh, F., Emadi, R., Valiani, A., Kharaziha, M., Poursamar, S.A., Bakhsheshi-Rad, H.R., Ismail, A.F., RamaKrishna, S., and Berto, F. (2020). Three-dimensional printing constructs based on the chitosan for tissue regeneration: State of the art, developing directions and prospect trends. Materials, 13.","DOI":"10.3390\/ma13112663"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zarandona, I., Bengoechea, C., \u00c1lvarez-Castillo, E., de la Caba, K., Guerrero, A., and Guerrero, P. (2021). 3D Printed Chitosan-Pectin Hydrogels: From Rheological Characterization to Scaffold Development and Assessment. Gels, 7.","DOI":"10.3390\/gels7040175"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mandal, S.C., Mandal, V., and Das, A.K. (2015). Chapter 7\u2014Innovative Extraction Process Design and Optimization Using Design of Experimental Approach. Essentials of Botanical Extraction, Academic Press.","DOI":"10.1016\/B978-0-12-802325-9.00007-0"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lloyd, D.K., and Bergum, J. (2014). Chapter 3\u2014Application of Quality by Design (QbD) to the Development and Validation of Analytical Methods. Specification of Drug Substances and Products, Elsevier.","DOI":"10.1016\/B978-0-08-098350-9.00003-5"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"132180","DOI":"10.1016\/j.foodchem.2022.132180","article-title":"Starch concentration is an important factor for controlling its digestibility during hot-extrusion 3D printing","volume":"379","author":"Zhang","year":"2022","journal-title":"Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.ijbiomac.2019.07.124","article-title":"Hydrogels based on ozonated cassava starch: Effect of ozone processing and gelatinization conditions on enhancing 3D-printing applications","volume":"138","author":"Maniglia","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"035001","DOI":"10.1088\/1758-5082\/5\/3\/035001","article-title":"Quantitative optimization of solid freeform deposition of aqueous hydrogels","volume":"5","author":"Kang","year":"2013","journal-title":"Biofabrication"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Sosa, A., Ram\u00edrez-Jim\u00e9nez, R.A., Rojo, L., Boulmedais, F., Aguilar, M.R., Criado-Gonzalez, M., and Hern\u00e1ndez, R. (2022). Optimization of the Rheological Properties of Self-Assembled Tripeptide\/Alginate\/Cellulose Hydrogels for 3D Printing. Polymers, 14.","DOI":"10.3390\/polym14112229"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Panaksri, A., and Tanadchangsaeng, N. (2021). Evaluation of 3D-printing scaffold fabrication on biosynthetic medium-chain-length polyhydroxyalkanoate terpolyester as biomaterial ink. Polymers, 13.","DOI":"10.3390\/polym13142222"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.polymer.2018.01.070","article-title":"Chemical modification and printability of shear thinning hydrogel inks for direct-write 3D printing","volume":"152","author":"Smith","year":"2018","journal-title":"Polymer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100011","DOI":"10.1016\/j.stlm.2021.100011","article-title":"Polymeric biomaterials for 3D printing in 711 medicine: An overview","volume":"2","author":"Pugliese","year":"2021","journal-title":"Ann. 3D Print. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jfoodeng.2016.01.025","article-title":"3D Printing Technologies Applied for Food Design: Status and Prospects","volume":"179","author":"Godoi","year":"2016","journal-title":"J. Food Eng."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jfoodeng.2017.04.017","article-title":"Impact of rheological properties of mashed potatoes on 3D printing","volume":"220","author":"Liu","year":"2018","journal-title":"J. Food Eng."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40824-021-00204-y","article-title":"3D printing PCL\/nHA bone scaffolds: Exploring the influence of material synthesis techniques","volume":"25","author":"Zimmerling","year":"2021","journal-title":"Biomater. Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/973\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:59:02Z","timestamp":1760119142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,4]]},"references-count":50,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24020973"],"URL":"https:\/\/doi.org\/10.3390\/ijms24020973","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,4]]}}}