{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T06:45:23Z","timestamp":1747205123437,"version":"3.40.5"},"posted":{"date-parts":[[2024,3,21]]},"group-title":"In Review","reference-count":85,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,3,20]]},"abstract":"<title>Abstract<\/title>\n        <p>Bioprinting approaches are of great promise for tissue engineering (TE) applications, given that they allow the fabrication of constructs able to mimic native tissues' mechanical and topographical features. In this study, a novel bioink comprising \u03ba-carrageenan (\u03bac), collagen, and magnetic nanoparticles (MNPs) was designed for 3D bioprinting applications. \u03bac is suitable for use in bioprinting due to its gelation and mechanical properties. Combining this polysaccharide with collagen and MNPs for remote stimulation of the printed scaffold, we successfully achieved a 3D-printed functional structure. Mechanical compressive tests yielded Young\u2019s moduli ranging from 8.25 to 18.4 kPa. The addition of collagen caused this value to decrease, as expected, while the addition of MNPs had an opposing effect. The hydrogels also exhibited water contents over 97% in all formulations. Rheological assessments indicated a sol-gel transition temperature at 23-25\u00baC, making these bioinks suitable for extrusion-based bioprinting at room temperature. Printability analyses demonstrated excellent fidelity and structural integrity of the printed constructs, in addition to a high mesenchymal stem\/stromal cell (MSC) viability after bioprinting. Finally, as proof-of-concept, it was observed that bioprinted MSCs stimulated with an external magnetic field of 80 mT were able to increase the number of tubes formed by human umbilical vein endothelial cells. In conclusion, this study constitutes a valuable approach for 3D bioprinting of multifunctional materials using novel bioink compositions, thus advancing TE technologies while creating new paths for future research in regenerative medicine applications.<\/p>","DOI":"10.21203\/rs.3.rs-4138126\/v1","type":"posted-content","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T11:51:34Z","timestamp":1711021894000},"source":"Crossref","is-referenced-by-count":1,"title":["Design of Magnetic \u03ba-Carrageenan-Collagen Bioinks for 3D Bioprinting"],"prefix":"10.21203","author":[{"given":"Duarte","family":"Almeida","sequence":"first","affiliation":[{"name":"Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}]},{"given":"Freya","family":"K\u00fcppers","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}]},{"given":"Afonso","family":"Gusm\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}]},{"given":"Ana C.","family":"Manjua","sequence":"additional","affiliation":[{"name":"Biosensors and Devices Lab, Biomedical Engineering Department, Institute for Complex Molecular Systems, Eindhoven Artificial Intelligence Systems Institute, Eindhoven University of Technology, Eindhoven, 5600 MB, The Netherlands"}]},{"given":"Catarina F.R.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}]},{"given":"Carla A.M.","family":"Portugal","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, Campus da Caparica, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4773-6771","authenticated-orcid":false,"given":"Jo\u00e3o C.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2079-2864","authenticated-orcid":false,"given":"Paola","family":"Sanjuan-Alberte","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5177-6237","authenticated-orcid":false,"given":"Frederico Castelo","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior T\u00e9cnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal"}]}],"member":"297","reference":[{"issue":"Elsevier","key":"ref1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/B978-0-12-816806-6.00010-8","article-title":"Hydrogels","author":"Wang W","year":"2020","unstructured":"Wang W, Narain R, Zeng H (2020) Hydrogels. Polym Sci Nanatechnol Elsevier203\u2013244. 10.1016\/B978-0-12-816806-6.00010-8","journal-title":"Polym Sci Nanatechnol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4161\/org.23395","article-title":"Biomimicry in biomedical research","volume":"8","author":"Zhang G","year":"2012","unstructured":"Zhang G (2012) Biomimicry in biomedical research. Organogenesis 8:101\u2013102","journal-title":"Organogenesis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"5409","DOI":"10.1016\/j.biomaterials.2009.06.045","article-title":"Naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineering","volume":"30","author":"Singelyn JM","year":"2009","unstructured":"Singelyn JM et al (2009) Naturally derived myocardial matrix as an injectable scaffold for cardiac tissue engineering. Biomaterials 30:5409\u20135416","journal-title":"Biomaterials"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jss.2015.11.012","article-title":"Chitosan hydrogels significantly limit left ventricular infarction and remodeling and preserve myocardial contractility","volume":"201","author":"Henning RJ","year":"2016","unstructured":"Henning RJ, Khan A, Jimenez E (2016) Chitosan hydrogels significantly limit left ventricular infarction and remodeling and preserve myocardial contractility. J Surg Res 201:490\u2013497","journal-title":"J Surg Res"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1016\/j.biomaterials.2008.03.016","article-title":"Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: Systematic modulation of a synthetic cell-responsive PEG-hydrogel","volume":"29","author":"Kraehenbuehl TP","year":"2008","unstructured":"Kraehenbuehl TP et al (2008) Three-dimensional extracellular matrix-directed cardioprogenitor differentiation: Systematic modulation of a synthetic cell-responsive PEG-hydrogel. Biomaterials 29:2757\u20132766","journal-title":"Biomaterials"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1600734","DOI":"10.1002\/biot.201600734","article-title":"X. 3D bioprinting and the current applications in tissue engineering","volume":"12","author":"Huang Y","year":"2017","unstructured":"Huang Y, Zhang X-F, Gao G, Yonezawa T, Cui (2017) X. 3D bioprinting and the current applications in tissue engineering. Biotechnol J 12:1600734","journal-title":"Biotechnol J"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.biotechadv.2015.12.011","article-title":"D.-H. 3D bioprinting for engineering complex tissues","volume":"34","author":"Mandrycky C","year":"2016","unstructured":"Mandrycky C, Wang Z, Kim K, Kim (2016) D.-H. 3D bioprinting for engineering complex tissues. Biotechnol Adv 34:422\u2013434","journal-title":"Biotechnol Adv"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3390\/bioengineering9030109","article-title":"3D Bioprinting of Novel \u03ba-Carrageenan Bioinks: An Algae-Derived Polysaccharide","volume":"9","author":"Marques DMC","year":"2022","unstructured":"Marques DMC et al (2022) 3D Bioprinting of Novel \u03ba-Carrageenan Bioinks: An Algae-Derived Polysaccharide. Bioengineering 9:109","journal-title":"Bioengineering"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s10811-018-1562-7","article-title":"Harvest optimization to assess sustainable growth and carrageenan yield of cultivated Kappaphycus alvarezii (Doty) Doty in Indian waters","volume":"31","author":"Periyasamy C","year":"2019","unstructured":"Periyasamy C, Subba Rao PV, Anantharaman P (2019) Harvest optimization to assess sustainable growth and carrageenan yield of cultivated Kappaphycus alvarezii (Doty) Doty in Indian waters. J Appl Phycol 31:587\u2013597","journal-title":"J Appl Phycol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/adhm.201200317","article-title":"Photocrosslinkable Kappa -Carrageenan Hydrogels for Tissue Engineering Applications","volume":"2","author":"Mihaila SM","year":"2013","unstructured":"Mihaila SM et al (2013) Photocrosslinkable Kappa -Carrageenan Hydrogels for Tissue Engineering Applications. Adv Healthc Mater 2:895\u2013907","journal-title":"Adv Healthc Mater"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s10719-019-09858-2","article-title":"Compositional and structural analysis of glycosaminoglycans in cell-derived extracellular matrices","volume":"36","author":"Silva JC","year":"2019","unstructured":"Silva JC et al (2019) Compositional and structural analysis of glycosaminoglycans in cell-derived extracellular matrices. Glycoconj J 36:141\u2013154","journal-title":"Glycoconj J"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1088\/1748-605X\/ace0ec","article-title":"Kappa-carrageenan based hybrid hydrogel for soft tissue engineering applications","author":"Safarpour F","year":"2023","unstructured":"Safarpour F et al (2023) Kappa-carrageenan based hybrid hydrogel for soft tissue engineering applications. Biomed Mater. 10.1088\/1748-605X\/ace0ec","journal-title":"Biomed Mater"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.colsurfb.2013.08.049","article-title":"Gelatin\u2013carrageenan hydrogels: Role of pore size distribution on drug delivery process","volume":"113","author":"Varghese JS","year":"2014","unstructured":"Varghese JS, Chellappa N, Fathima NN (2014) Gelatin\u2013carrageenan hydrogels: Role of pore size distribution on drug delivery process. Colloids Surf B Biointerfaces 113:346\u2013351","journal-title":"Colloids Surf B Biointerfaces"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"560","DOI":"10.3390\/polym12030560","article-title":"Physically Crosslinked Poly (Vinyl Alcohol)\/Kappa-Carrageenan Hydrogels: Structure and Applications","volume":"12","author":"Croitoru C","year":"2020","unstructured":"Croitoru C et al (2020) Physically Crosslinked Poly (Vinyl Alcohol)\/Kappa-Carrageenan Hydrogels: Structure and Applications. Polymers 12:560","journal-title":"Polymers"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1039\/C7BM00765E","article-title":"Bioinks for 3D bioprinting: an overview","volume":"6","author":"Gungor-Ozkerim PS","year":"2018","unstructured":"Gungor-Ozkerim PS, Inci I, Zhang YS, Khademhosseini A, Dokmeci MR (2018) Bioinks for 3D bioprinting: an overview. Biomater Sci 6:915\u2013946","journal-title":"Biomater Sci"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.3390\/biomedicines9091137","article-title":"Collagen Bioinks for Bioprinting: A Systematic Review of Hydrogel Properties, Bioprinting Parameters, Protocols, and Bioprinted Structure Characteristics","volume":"9","author":"Stepanovska J","year":"2021","unstructured":"Stepanovska J, Supova M, Hanzalek K, Broz A, Matejka R (2021) Collagen Bioinks for Bioprinting: A Systematic Review of Hydrogel Properties, Bioprinting Parameters, Protocols, and Bioprinted Structure Characteristics. Biomedicines 9:1137","journal-title":"Biomedicines"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.biomaterials.2017.04.019","article-title":"Del Campo, A. 3D bioprinting of structural proteins","volume":"134","author":"W\u0142odarczyk-Biegun MK","year":"2017","unstructured":"W\u0142odarczyk-Biegun MK (2017) Del Campo, A. 3D bioprinting of structural proteins. Biomaterials 134:180\u2013201","journal-title":"Biomaterials"},{"key":"ref18","article-title":"Petrovich Domogatskiy, S. Collagen as Bioink for Bioprinting: A Comprehensive Review","volume":"6","author":"Olegovich Osidak E","year":"2020","unstructured":"Olegovich Osidak E, Kozhukhov I, Sergeevna Osidak V (2020) M. & Petrovich Domogatskiy, S. Collagen as Bioink for Bioprinting: A Comprehensive Review. Int J Bioprinting 6","journal-title":"Int J Bioprinting"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"12010","DOI":"10.1021\/acsami.9b21713","article-title":"Dual pH-Responsive Hydrogel Actuator for Lipophilic Drug Delivery","volume":"12","author":"Han Z","year":"2020","unstructured":"Han Z et al (2020) Dual pH-Responsive Hydrogel Actuator for Lipophilic Drug Delivery. ACS Appl Mater Interfaces 12:12010\u201312017","journal-title":"ACS Appl Mater Interfaces"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3390\/gels7030077","article-title":"Thermo-Responsive Hydrogels: From Recent Progress to Biomedical Applications","volume":"7","author":"Zhang K","year":"2021","unstructured":"Zhang K, Xue K, Loh XJ (2021) Thermo-Responsive Hydrogels: From Recent Progress to Biomedical Applications. Gels 7:77","journal-title":"Gels"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jconrel.2020.08.051","article-title":"Conducting polymer hydrogels for electrically responsive drug delivery","volume":"328","author":"Bansal M","year":"2020","unstructured":"Bansal M et al (2020) Conducting polymer hydrogels for electrically responsive drug delivery. J Controlled Release 328:192\u2013209","journal-title":"J Controlled Release"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.3390\/polym13111883","article-title":"Magnetic Field Dynamic Strategies for the Improved Control of the Angiogenic Effect of Mesenchymal Stromal Cells","volume":"13","author":"Manjua AC","year":"2021","unstructured":"Manjua AC, Cabral JMS, Ferreira FC, Portugal CAM (2021) Magnetic Field Dynamic Strategies for the Improved Control of the Angiogenic Effect of Mesenchymal Stromal Cells. Polymers 13:1883","journal-title":"Polymers"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/gels6020014","article-title":"Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery","volume":"6","author":"Askari E","year":"2020","unstructured":"Askari E et al (2020) Stimuli-Responsive Hydrogels for Local Post-Surgical Drug Delivery. Gels 6:14","journal-title":"Gels"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"120299","DOI":"10.1016\/j.biomaterials.2020.120299","article-title":"Injectable ferrimagnetic silk fibroin hydrogel for magnetic hyperthermia ablation of deep tumor","volume":"259","author":"Qian K-Y","year":"2020","unstructured":"Qian K-Y et al (2020) Injectable ferrimagnetic silk fibroin hydrogel for magnetic hyperthermia ablation of deep tumor. Biomaterials 259:120299","journal-title":"Biomaterials"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"9908","DOI":"10.1021\/acsami.3c18877","article-title":"M. Heparinized Acellular Hydrogels for Magnetically Induced Wound Healing Applications","volume":"16","author":"Pires F","year":"2024","unstructured":"Pires F, Silva JC, Ferreira FC, Portugal CA (2024) M. Heparinized Acellular Hydrogels for Magnetically Induced Wound Healing Applications. ACS Appl Mater Interfaces 16:9908\u20139924","journal-title":"ACS Appl Mater Interfaces"},{"key":"ref26","doi-asserted-by":"crossref","DOI":"10.36922\/ijb.0965","article-title":"C. 3D (bio)printing of magnetic hydrogels: Formulation and applications in tissue engineering","author":"Almeida D","year":"2023","unstructured":"Almeida D, Sanjuan-Alberte P, Silva JC, Ferreira F (2023) C. 3D (bio)printing of magnetic hydrogels: Formulation and applications in tissue engineering. Int J Bioprinting","journal-title":"Int J Bioprinting"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1002\/pi.5170","article-title":"Recent advances in magnetic hydrogels: Recent advances in magnetic hydrogels","volume":"65","author":"Zhang J","year":"2016","unstructured":"Zhang J, Huang Q, Du J (2016) Recent advances in magnetic hydrogels: Recent advances in magnetic hydrogels. Polym Int 65:1365\u20131372","journal-title":"Polym Int"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1080\/14686996.2021.1927834","article-title":"Magnetic stimulation of the angiogenic potential of mesenchymal stromal cells in vascular tissue engineering","volume":"22","author":"Manjua AC","year":"2021","unstructured":"Manjua AC, Cabral JMS, Portugal CAM, Ferreira FC (2021) Magnetic stimulation of the angiogenic potential of mesenchymal stromal cells in vascular tissue engineering. Sci Technol Adv Mater 22:461\u2013480","journal-title":"Sci Technol Adv Mater"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e115202","DOI":"10.1371\/journal.pone.0115202","article-title":"Magnetic Cross-Linked Enzyme Aggregates (mCLEAs) of Candida antarctica Lipase: An Efficient and Stable Biocatalyst for Biodiesel Synthesis","volume":"9","author":"Cruz-Izquierdo \u00c1","year":"2014","unstructured":"Cruz-Izquierdo \u00c1, Pic\u00f3 EA, L\u00f3pez C, Serra JL, Llama MJ (2014) Magnetic Cross-Linked Enzyme Aggregates (mCLEAs) of Candida antarctica Lipase: An Efficient and Stable Biocatalyst for Biodiesel Synthesis. PLoS ONE 9:e115202","journal-title":"PLoS ONE"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/jbm.b.33894","article-title":"Bone extracellular matrix hydrogel enhances osteogenic differentiation of C2C12 myoblasts and mouse primary calvarial cells: Bone ECM Hydrogel and Osteogenic Differentiation","volume":"106","author":"Alom N","year":"2018","unstructured":"Alom N, Peto H, Kirkham GR, Shakesheff KM, White LJ (2018) Bone extracellular matrix hydrogel enhances osteogenic differentiation of C2C12 myoblasts and mouse primary calvarial cells: Bone ECM Hydrogel and Osteogenic Differentiation. J Biomed Mater Res B Appl Biomater 106:900\u2013908","journal-title":"J Biomed Mater Res B Appl Biomater"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.31224\/2916","author":"Gusm\u00e3o A","year":"2023","unstructured":"Gusm\u00e3o A (2023) Designing and Prototyping a 3D Printer for Multi-Extrusion of Thermo- and Photocurable Hydrogels: Enabling Affordable and Wider Access to Bioprinting. https:\/\/engrxiv.org\/preprint\/view\/2916\/version\/4158 10.31224\/2916"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1007\/s10719-020-09911-5","article-title":"Glycosaminoglycan remodeling during chondrogenic differentiation of human bone marrow\u2013\/synovial-derived mesenchymal stem\/stromal cells under normoxia and hypoxia","volume":"37","author":"Silva JC","year":"2020","unstructured":"Silva JC et al (2020) Glycosaminoglycan remodeling during chondrogenic differentiation of human bone marrow\u2013\/synovial-derived mesenchymal stem\/stromal cells under normoxia and hypoxia. Glycoconj J 37:345\u2013360","journal-title":"Glycoconj J"},{"year":"2012","author":"Carpentier G","key":"ref33","unstructured":"Carpentier G (2012) Angiogenesis Analyzer for ImageJ. http:\/\/imagej.nih.gov\/ij\/macros\/toolsets\/Angiogenesis%20Analyzer.txt"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1021\/ar200113c","article-title":"Nanoparticle \u03b6 -Potentials","volume":"45","author":"Doane TL","year":"2012","unstructured":"Doane TL, Chuang C-H, Hill RJ, Burda C (2012) Nanoparticle \u03b6 -Potentials. Acc Chem Res 45:317\u2013326","journal-title":"Acc Chem Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.3390\/molecules26061744","article-title":"The Synthesis Methodology of PEGylated Fe3O4@Ag Nanoparticles Supported by Their Physicochemical Evaluation","volume":"26","author":"K\u0119dzierska M","year":"2021","unstructured":"K\u0119dzierska M et al (2021) The Synthesis Methodology of PEGylated Fe3O4@Ag Nanoparticles Supported by Their Physicochemical Evaluation. Molecules 26:1744","journal-title":"Molecules"},{"year":"2015","author":"Darwish MSA","key":"ref36","unstructured":"Darwish MSA, Nguyen NHA, \u0160evc\u016f A, Stibor I (2015) Functionalized Magnetic Nanoparticles and Their Effect on Escherichia coli and Staphylococcus aureus. J. Nanomater. 1\u201310 (2015)"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.3390\/nano11112888","article-title":"Influence of Coating and Size of Magnetic Nanoparticles on Cellular Uptake for In Vitro MRI","volume":"11","author":"Cort\u00e9s-Llanos B","year":"2021","unstructured":"Cort\u00e9s-Llanos B et al (2021) Influence of Coating and Size of Magnetic Nanoparticles on Cellular Uptake for In Vitro MRI. Nanomaterials 11:2888","journal-title":"Nanomaterials"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.colsurfb.2012.02.022","article-title":"Probing nanoparticle interactions in cell culture media","volume":"95","author":"Sabuncu AC","year":"2012","unstructured":"Sabuncu AC et al (2012) Probing nanoparticle interactions in cell culture media. Colloids Surf B Biointerfaces 95:96\u2013102","journal-title":"Colloids Surf B Biointerfaces"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12951-015-0090-8","article-title":"Bioactive magnetic near Infra-Red fluorescent core-shell iron oxide\/human serum albumin nanoparticles for controlled release of growth factors for augmentation of human mesenchymal stem cell growth and differentiation","volume":"13","author":"Levy I","year":"2015","unstructured":"Levy I et al (2015) Bioactive magnetic near Infra-Red fluorescent core-shell iron oxide\/human serum albumin nanoparticles for controlled release of growth factors for augmentation of human mesenchymal stem cell growth and differentiation. J Nanobiotechnol 13:34","journal-title":"J Nanobiotechnol"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.5772\/46121","author":"Ankamwar B","year":"2012","unstructured":"Ankamwar B (2012) Size and Shape Effect on Biomedical Applications of Nanomaterials. in Biomedical Engineering - Technical Applications in Medicine (ed. Hudak, R.)InTech, 10.5772\/46121"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"15631","DOI":"10.1039\/D1NR03484G","article-title":"How size, shape and assembly of magnetic nanoparticles give rise to different hyperthermia scenarios","volume":"13","author":"Gavil\u00e1n H","year":"2021","unstructured":"Gavil\u00e1n H et al (2021) How size, shape and assembly of magnetic nanoparticles give rise to different hyperthermia scenarios. Nanoscale 13:15631\u201315646","journal-title":"Nanoscale"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1002\/smll.200500006","article-title":"Properties, and Applications of Iron Nanoparticles","volume":"1","author":"Huber DL","year":"2005","unstructured":"Huber DL, Synthesis (2005) Properties, and Applications of Iron Nanoparticles. Small 1:482\u2013501","journal-title":"Small"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s13287-022-02808-0","article-title":"Application of magnetic nanoparticles in cell therapy","volume":"13","author":"Chen Y","year":"2022","unstructured":"Chen Y, Hou S (2022) Application of magnetic nanoparticles in cell therapy. Stem Cell Res Ther 13:135","journal-title":"Stem Cell Res Ther"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"101574","DOI":"10.1016\/j.progpolymsci.2022.101574","article-title":"3D printed magnetic polymer composite hydrogels for hyperthermia and magnetic field driven structural manipulation","volume":"131","author":"Ganguly S","year":"2022","unstructured":"Ganguly S, Margel S (2022) 3D printed magnetic polymer composite hydrogels for hyperthermia and magnetic field driven structural manipulation. Prog Polym Sci 131:101574","journal-title":"Prog Polym Sci"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.msec.2016.09.039","article-title":"Super-paramagnetic responsive silk fibroin\/chitosan\/magnetite scaffolds with tunable pore structures for bone tissue engineering applications","volume":"70","author":"Aliramaji S","year":"2017","unstructured":"Aliramaji S, Zamanian A, Mozafari M (2017) Super-paramagnetic responsive silk fibroin\/chitosan\/magnetite scaffolds with tunable pore structures for bone tissue engineering applications. Mater Sci Eng C 70:736\u2013744","journal-title":"Mater Sci Eng C"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1177\/0883911517693635","article-title":"Magnetic silk fibroin e-gel scaffolds for bone tissue engineering applications","volume":"32","author":"Karahalilo\u011flu Z","year":"2017","unstructured":"Karahalilo\u011flu Z, Yal\u00e7\u0131n E, Demirbilek M, Denkba\u015f EB (2017) Magnetic silk fibroin e-gel scaffolds for bone tissue engineering applications. J Bioact Compat Polym 32:596\u2013614","journal-title":"J Bioact Compat Polym"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.jallcom.2016.09.234","article-title":"A novel composite of collagen-hydroxyapatite\/kappa-carrageenan","volume":"693","author":"Feng W","year":"2017","unstructured":"Feng W et al (2017) A novel composite of collagen-hydroxyapatite\/kappa-carrageenan. J Alloys Compd 693:482\u2013489","journal-title":"J Alloys Compd"},{"key":"ref48","first-page":"361","article-title":"Young\u2019s modulus of collagen at slow displacement rates","volume":"20","author":"Lopez-Garcia MDC","year":"2010","unstructured":"Lopez-Garcia MDC, Beebe DJ, Crone WC (2010) Young\u2019s modulus of collagen at slow displacement rates. Biomed Mater Eng 20:361\u2013369","journal-title":"Biomed Mater Eng"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1021\/acsbiomaterials.6b00288","article-title":"J. 3D Bioprinting of Spatially Heterogeneous Collagen Constructs for Cartilage Tissue Engineering","volume":"2","author":"Rhee S","year":"2016","unstructured":"Rhee S, Puetzer JL, Mason BN, Reinhart-King CA, Bonassar L (2016) J. 3D Bioprinting of Spatially Heterogeneous Collagen Constructs for Cartilage Tissue Engineering. ACS Biomater Sci Eng 2:1800\u20131805","journal-title":"ACS Biomater Sci Eng"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1007\/s10237-016-0763-8","article-title":"Biomechanical properties of breast tissue, a state-of-the-art review","volume":"15","author":"Rami\u00e3o NG","year":"2016","unstructured":"Rami\u00e3o NG et al (2016) Biomechanical properties of breast tissue, a state-of-the-art review. Biomech Model Mechanobiol 15:1307\u20131323","journal-title":"Biomech Model Mechanobiol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1109\/86.788463","article-title":"T. Effective elastic properties for lower limb soft tissues from manual indentation experiment","volume":"7","author":"Yongping Z","year":"1999","unstructured":"Yongping Z, Mak AF (1999) T. Effective elastic properties for lower limb soft tissues from manual indentation experiment. IEEE Trans Rehabil Eng 7:257\u2013267","journal-title":"IEEE Trans Rehabil Eng"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"8483","DOI":"10.1038\/s41598-022-12143-2","article-title":"Human induced mesenchymal stem cells display increased sensitivity to matrix stiffness","volume":"12","author":"Gultian KA","year":"2022","unstructured":"Gultian KA et al (2022) Human induced mesenchymal stem cells display increased sensitivity to matrix stiffness. Sci Rep 12:8483","journal-title":"Sci Rep"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"166395","DOI":"10.1016\/j.jmmm.2020.166395","article-title":"Determination of the Young\u2019s modulus for alginate-based hydrogel with magnetite-particles depending on storage conditions and particle concentration","volume":"501","author":"Czichy C","year":"2020","unstructured":"Czichy C, Spangenberg J, G\u00fcnther S, Gelinsky M, Odenbach S (2020) Determination of the Young\u2019s modulus for alginate-based hydrogel with magnetite-particles depending on storage conditions and particle concentration. J Magn Magn Mater 501:166395","journal-title":"J Magn Magn Mater"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"10292","DOI":"10.1021\/acsami.8b20937","article-title":"Adhesive Tough Magnetic Hydrogels with High Fe 3 O 4 Content","volume":"11","author":"Hu X","year":"2019","unstructured":"Hu X et al (2019) Adhesive Tough Magnetic Hydrogels with High Fe 3 O 4 Content. ACS Appl Mater Interfaces 11:10292\u201310300","journal-title":"ACS Appl Mater Interfaces"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"034102","DOI":"10.1088\/1758-5090\/abfaee","article-title":"A digital light processing 3D printed magnetic bioreactor system using silk magnetic bioink","volume":"13","author":"Ajiteru O","year":"2021","unstructured":"Ajiteru O et al (2021) A digital light processing 3D printed magnetic bioreactor system using silk magnetic bioink. Biofabrication 13:034102","journal-title":"Biofabrication"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1021\/acsbiomaterials.0c01371","article-title":"Bioprinting of Magnetically Deformable Scaffolds","volume":"7","author":"Spangenberg J","year":"2021","unstructured":"Spangenberg J et al (2021) Bioprinting of Magnetically Deformable Scaffolds. ACS Biomater Sci Eng 7:648\u2013662","journal-title":"ACS Biomater Sci Eng"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1039\/c3sm27413f","article-title":"I. H. Ionic-covalent entanglement hydrogels from gellan gum, carrageenan and an epoxy-amine","volume":"9","author":"Stevens L","year":"2013","unstructured":"Stevens L, Calvert P, Wallace GG, Panhuis M (2013) I. H. Ionic-covalent entanglement hydrogels from gellan gum, carrageenan and an epoxy-amine. Soft Matter 9:3009","journal-title":"Soft Matter"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.3390\/polym12051128","article-title":"The Ophthalmic Performance of Hydrogel Contact Lenses Loaded with Silicone Nanoparticles","volume":"12","author":"Tran N-P-D","year":"2020","unstructured":"Tran N-P-D, Yang M-C (2020) The Ophthalmic Performance of Hydrogel Contact Lenses Loaded with Silicone Nanoparticles. Polymers 12:1128","journal-title":"Polymers"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"6861","DOI":"10.1007\/s10570-019-02572-0","article-title":"Smart cellulose-derived magnetic hydrogel with rapid swelling and deswelling properties for remotely controlled drug release","volume":"26","author":"Lin F","year":"2019","unstructured":"Lin F et al (2019) Smart cellulose-derived magnetic hydrogel with rapid swelling and deswelling properties for remotely controlled drug release. Cellulose 26:6861\u20136877","journal-title":"Cellulose"},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.5772\/64301","author":"Bahram M","year":"2016","unstructured":"Bahram M, Mohseni N, Moghtader M (2016) An Introduction to Hydrogels and Some Recent Applications. in Emerging Concepts in Analysis and Applications of Hydrogels (ed. Majee, S. B.)InTech, 10.5772\/64301"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.3390\/ma12203323","article-title":"Smart Hydrogels in Tissue Engineering and Regenerative Medicine","volume":"12","author":"Mantha S","year":"2019","unstructured":"Mantha S et al (2019) Smart Hydrogels in Tissue Engineering and Regenerative Medicine. Materials 12:3323","journal-title":"Materials"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"1900203","DOI":"10.1002\/adhm.201900203","article-title":"Magnetic Hydrogel with Optimally Adaptive Functions for Breast Cancer Recurrence Prevention","volume":"8","author":"Gao F","year":"2019","unstructured":"Gao F et al (2019) Magnetic Hydrogel with Optimally Adaptive Functions for Breast Cancer Recurrence Prevention. Adv Healthc Mater 8:1900203","journal-title":"Adv Healthc Mater"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"111555","DOI":"10.1016\/j.msec.2020.111555","article-title":"Preparation of a recombinant collagen-peptide (RHC)-conjugated chitosan thermosensitive hydrogel for wound healing","volume":"119","author":"Deng A","year":"2021","unstructured":"Deng A et al (2021) Preparation of a recombinant collagen-peptide (RHC)-conjugated chitosan thermosensitive hydrogel for wound healing. Mater Sci Eng C 119:111555","journal-title":"Mater Sci Eng C"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"11051","DOI":"10.1021\/acsami.1c19889","article-title":"Angiogenic Hyaluronic Acid Hydrogels with Curcumin-Coated Magnetic Nanoparticles for Tissue Repair","volume":"14","author":"Daya R","year":"2022","unstructured":"Daya R, Xu C, Nguyen N-YT, Liu HH (2022) Angiogenic Hyaluronic Acid Hydrogels with Curcumin-Coated Magnetic Nanoparticles for Tissue Repair. ACS Appl Mater Interfaces 14:11051\u201311067","journal-title":"ACS Appl Mater Interfaces"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s40820-023-01043-3","article-title":"Self-Healing Liquid Metal Magnetic Hydrogels for Smart Feedback Sensors and High-Performance Electromagnetic Shielding","volume":"15","author":"Zhao B","year":"2023","unstructured":"Zhao B et al (2023) Self-Healing Liquid Metal Magnetic Hydrogels for Smart Feedback Sensors and High-Performance Electromagnetic Shielding. Nano-Micro Lett 15:79","journal-title":"Nano-Micro Lett"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"2000186","DOI":"10.1002\/aisy.202000186","article-title":"Magnetically Controlled Soft Robotics Utilizing Elastomers and Gels in Actuation: A Review","volume":"3","author":"Chung H","year":"2021","unstructured":"Chung H, Parsons AM, Zheng L (2021) Magnetically Controlled Soft Robotics Utilizing Elastomers and Gels in Actuation: A Review. Adv Intell Syst 3:2000186","journal-title":"Adv Intell Syst"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"1804647","DOI":"10.1002\/adfm.201804647","article-title":"A Stimuli-Responsive Nanocomposite for 3D Anisotropic Cell\u2010Guidance and Magnetic Soft Robotics","volume":"29","author":"Tognato R","year":"2019","unstructured":"Tognato R et al (2019) A Stimuli-Responsive Nanocomposite for 3D Anisotropic Cell\u2010Guidance and Magnetic Soft Robotics. Adv Funct Mater 29:1804647","journal-title":"Adv Funct Mater"},{"key":"ref68","first-page":"102506","article-title":"4D printing of patterned multimaterial magnetic hydrogel actuators","volume":"49","author":"Simi\u0144ska-Stanny J","year":"2022","unstructured":"Simi\u0144ska-Stanny J et al (2022) 4D printing of patterned multimaterial magnetic hydrogel actuators. Addit Manuf 49:102506","journal-title":"Addit Manuf"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1177\/0883911503018001004","article-title":"Hysteresis During Sol-Gel and Gel-Sol Phase Transitions of k-Carrageenan: A Photon Transmission Study","volume":"18","author":"Kara S","year":"2003","unstructured":"Kara S, Tamerler C, Bermek H, Pekcan \u00d6 (2003) Hysteresis During Sol-Gel and Gel-Sol Phase Transitions of k-Carrageenan: A Photon Transmission Study. J Bioact Compat Polym 18:33\u201344","journal-title":"J Bioact Compat Polym"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"111316","DOI":"10.1016\/j.jfoodeng.2022.111316","article-title":"Correlating 3D printing performance with sol-gel transition based on thermo-responsive k-carrageenan affected by fructose","volume":"340","author":"Zhu Y","year":"2023","unstructured":"Zhu Y, Di W, Song M, Chitrakar B, Liu Z (2023) Correlating 3D printing performance with sol-gel transition based on thermo-responsive k-carrageenan affected by fructose. J Food Eng 340:111316","journal-title":"J Food Eng"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jcis.2008.04.051","article-title":"Effects of magnetite nanoparticles on the thermorheological properties of carrageenan hydrogels","volume":"324","author":"Daniel-da-Silva AL","year":"2008","unstructured":"Daniel-da-Silva AL et al (2008) Effects of magnetite nanoparticles on the thermorheological properties of carrageenan hydrogels. J Colloid Interface Sci 324:205\u2013211","journal-title":"J Colloid Interface Sci"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1021\/bm0610065","article-title":"Rheological Characterization of in Situ Crosslinkable Hydrogels Formulated from Oxidized Dextran and N -Carboxyethyl Chitosan","volume":"8","author":"Weng L","year":"2007","unstructured":"Weng L, Chen X, Chen W (2007) Rheological Characterization of in Situ Crosslinkable Hydrogels Formulated from Oxidized Dextran and N -Carboxyethyl Chitosan. Biomacromolecules 8:1109\u20131115","journal-title":"Biomacromolecules"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.procir.2015.07.037","article-title":"Viscoelastic Properties of Rapid Prototyped Magnetic Nanocomposite Scaffolds for Osteochondral Tissue Regeneration","volume":"49","author":"Santis R","year":"2016","unstructured":"De Santis R et al (2016) Viscoelastic Properties of Rapid Prototyped Magnetic Nanocomposite Scaffolds for Osteochondral Tissue Regeneration. Procedia CIRP 49:76\u201382","journal-title":"Procedia CIRP"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.jpha.2021.02.001","article-title":"Printability\u2013A key issue in extrusion-based bioprinting","volume":"11","author":"Naghieh S","year":"2021","unstructured":"Naghieh S, Chen X (2021) Printability\u2013A key issue in extrusion-based bioprinting. J Pharm Anal 11:564\u2013579","journal-title":"J Pharm Anal"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"1900971","DOI":"10.1002\/adfm.201900971","article-title":"3D Printing of Multifunctional Hydrogels","volume":"29","author":"Chen Z","year":"2019","unstructured":"Chen Z et al (2019) 3D Printing of Multifunctional Hydrogels. Adv Funct Mater 29:1900971","journal-title":"Adv Funct Mater"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.msec.2019.04.030","article-title":"Engineering microenvironments towards harnessing pro-angiogenic potential of mesenchymal stem cells","volume":"102","author":"Nasser M","year":"2019","unstructured":"Nasser M, Wu Y, Danaoui Y, Ghosh G (2019) Engineering microenvironments towards harnessing pro-angiogenic potential of mesenchymal stem cells. Mater Sci Eng C 102:75\u201384","journal-title":"Mater Sci Eng C"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"8758","DOI":"10.1038\/s41598-018-27098-6","article-title":"Regulation of Mesenchymal Stem Cell Differentiation by Nanopatterning of Bulk Metallic Glass","volume":"8","author":"Loye AM","year":"2018","unstructured":"Loye AM et al (2018) Regulation of Mesenchymal Stem Cell Differentiation by Nanopatterning of Bulk Metallic Glass. Sci Rep 8:8758","journal-title":"Sci Rep"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"035010","DOI":"10.1088\/1758-5090\/ab0692","article-title":"Wood-based nanocellulose and bioactive glass modified gelatin\u2013alginate bioinks for 3D bioprinting of bone cells","volume":"11","author":"Ojansivu M","year":"2019","unstructured":"Ojansivu M et al (2019) Wood-based nanocellulose and bioactive glass modified gelatin\u2013alginate bioinks for 3D bioprinting of bone cells. Biofabrication 11:035010","journal-title":"Biofabrication"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"15976","DOI":"10.1021\/acsami.9b19037","article-title":"Nanoengineered Osteoinductive Bioink for 3D Bioprinting Bone Tissue","volume":"12","author":"Chimene D","year":"2020","unstructured":"Chimene D et al (2020) Nanoengineered Osteoinductive Bioink for 3D Bioprinting Bone Tissue. ACS Appl Mater Interfaces 12:15976\u201315988","journal-title":"ACS Appl Mater Interfaces"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1039\/c2sm06994f","article-title":"New suitable for tissue reconstruction injectable chitosan\/collagen-based hydrogels","volume":"8","author":"Li X","year":"2012","unstructured":"Li X, Ma X, Fan D, Zhu C (2012) New suitable for tissue reconstruction injectable chitosan\/collagen-based hydrogels. Soft Matter 8:3781","journal-title":"Soft Matter"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1016\/j.nano.2017.06.002","article-title":"Multifunctional magnetic-responsive hydrogels to engineer tendon-to-bone interface","volume":"14","author":"Silva ED","year":"2018","unstructured":"Silva ED et al (2018) Multifunctional magnetic-responsive hydrogels to engineer tendon-to-bone interface. Nanomed Nanotechnol Biol Med 14:2375\u20132385","journal-title":"Nanomed Nanotechnol Biol Med"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S1000-1948(07)60023-9","article-title":"Effects of static magnetic field on human umbilical vessel endothelial cell","volume":"22","author":"Li F","year":"2007","unstructured":"Li F et al (2007) Effects of static magnetic field on human umbilical vessel endothelial cell. J Med Coll PLA 22:106\u2013110","journal-title":"J Med Coll PLA"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/bem.20246","article-title":"Effects of a moderate-intensity static magnetic field on VEGF\u2010A stimulated endothelial capillary tubule formation in vitro","volume":"27","author":"Okano H","year":"2006","unstructured":"Okano H, Onmori R, Tomita N, Ikada Y (2006) Effects of a moderate-intensity static magnetic field on VEGF\u2010A stimulated endothelial capillary tubule formation in vitro. Bioelectromagnetics 27:628\u2013640","journal-title":"Bioelectromagnetics"},{"year":"1995","author":"Paper DH","key":"ref84","unstructured":"Paper DH, Vogl H, Franz G, Hoffman R (1995) Defined carrageenan derivatives as angiogenesis inhibitors. Macromol. Symp. 99, 219\u2013225"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1177\/0885328218795569","article-title":"Carrageenan hydrogel as a scaffold for skin-derived multipotent stromal cells delivery","volume":"33","author":"Rode MP","year":"2018","unstructured":"Rode MP et al (2018) Carrageenan hydrogel as a scaffold for skin-derived multipotent stromal cells delivery. J Biomater Appl 33:422\u2013434","journal-title":"J Biomater Appl"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4138126\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4138126\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T11:52:07Z","timestamp":1711021927000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-4138126\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,21]]},"references-count":85,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-4138126\/v1","relation":{},"subject":[],"published":{"date-parts":[[2024,3,21]]},"subtype":"preprint"}}