{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:24:32Z","timestamp":1777569872703,"version":"3.51.4"},"reference-count":62,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology (FCT)","doi-asserted-by":"publisher","award":["PD\/BD\/143044\/2018"],"award-info":[{"award-number":["PD\/BD\/143044\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology (FCT)","doi-asserted-by":"publisher","award":["SFRH\/BPD\/94277\/2013"],"award-info":[{"award-number":["SFRH\/BPD\/94277\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology (FCT)","doi-asserted-by":"publisher","award":["EAPA_151\/2016"],"award-info":[{"award-number":["EAPA_151\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ERDF under the scope of the Atlantic Area Program","award":["PD\/BD\/143044\/2018"],"award-info":[{"award-number":["PD\/BD\/143044\/2018"]}]},{"name":"ERDF under the scope of the Atlantic Area Program","award":["SFRH\/BPD\/94277\/2013"],"award-info":[{"award-number":["SFRH\/BPD\/94277\/2013"]}]},{"name":"ERDF under the scope of the Atlantic Area Program","award":["EAPA_151\/2016"],"award-info":[{"award-number":["EAPA_151\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Marine origin polymers represent a sustainable and natural alternative to mammal counterparts regarding the biomedical application due to their similarities with proteins and polysaccharides present in extracellular matrix (ECM) in humans and can reduce the risks associated with zoonosis and overcoming social- and religious-related constraints. In particular, collagen-based biomaterials have been widely explored in tissue engineering scaffolding applications, where cryogels are of particular interest as low temperature avoids protein denaturation. However, little is known about the influence of the parameters regarding their behavior, i.e., how they can influence each other toward improving their physical and chemical properties. Factorial design of experiments (DoE) and response surface methodology (RSM) emerge as tools to overcome these difficulties, which are statistical tools to find the most influential parameter and optimize processes. In this work, we hypothesized that a design of experiments (DoE) model would be able to support the optimization of the collagen-chitosan-fucoidan cryogel manufacturing. Therefore, the parameters temperature (A), collagen concentration (B), and fucoidan concentration (C) were carefully considered to be applied to the Box\u2013Behnken design (three factors and three levels). Data obtained on rheological oscillatory measurements, as well as on the evaluation of antioxidant concentration and adenosine triphosphate (ATP) concentration, showed that fucoidan concentration could significantly influence collagen-chitosan-fucoidan cryogel formation, creating a stable internal polymeric network promoted by ionic crosslinking bonds. Additionally, the effect of temperature significantly contributed to rheological oscillatory properties. Overall, the condition that allowed us to have better results, from an optimization point of view according to the DoE, were the gels produced at \u221280 \u00b0C and composed of 5% of collagen, 3% of chitosan, and 10% fucoidan. Therefore, the proposed DoE model was considered suitable for predicting the best parameter combinations needed to develop these cryogels.<\/jats:p>","DOI":"10.3390\/polym14102026","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T21:36:06Z","timestamp":1652736966000},"page":"2026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Design of Experiments (DoE) Approach to Optimize Cryogel Manufacturing for Tissue Engineering Applications"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3115-0012","authenticated-orcid":false,"given":"Duarte Nuno","family":"Carvalho","sequence":"first","affiliation":[{"name":"3B\u2019s Research Group, I3B\u2019s\u2014Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2014P.T. Government Associate Laboratory, Braga, 4805-017 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-1310","authenticated-orcid":false,"given":"Cristiana","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3B\u2019s\u2014Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2014P.T. Government Associate Laboratory, Braga, 4805-017 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7052-8837","authenticated-orcid":false,"given":"Joaquim Miguel","family":"Oliveira","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3B\u2019s\u2014Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2014P.T. Government Associate Laboratory, Braga, 4805-017 Guimar\u00e3es, Portugal"}]},{"given":"David S.","family":"Williams","sequence":"additional","affiliation":[{"name":"Jellagen Limited, Unit G6, Capital Business Park, Parkway, St. Mellons, Cardiff CF3 2PY, UK"}]},{"given":"Andrew","family":"Mearns-Spragg","sequence":"additional","affiliation":[{"name":"Jellagen Limited, Unit G6, Capital Business Park, Parkway, St. Mellons, Cardiff CF3 2PY, UK"}]},{"given":"Rui L.","family":"Reis","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3B\u2019s\u2014Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2014P.T. Government Associate Laboratory, Braga, 4805-017 Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8520-603X","authenticated-orcid":false,"given":"Tiago H.","family":"Silva","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3B\u2019s\u2014Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Barco, 4805-017 Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2014P.T. Government Associate Laboratory, Braga, 4805-017 Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Zhou, D., Chen, J., Zhang, X., Li, X., Zhao, W., and Xu, T. (2019). Biomaterials Based on Marine Resources for 3D Bioprinting Applications. Mar. 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