{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T03:42:08Z","timestamp":1776483728019,"version":"3.51.2"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/145455\/2019"],"award-info":[{"award-number":["SFRH\/BD\/145455\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BPD\/121526\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/121526\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/FIS\/04650\/2020"],"award-info":[{"award-number":["UID\/FIS\/04650\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/BIO\/04469\/2020"],"award-info":[{"award-number":["UID\/BIO\/04469\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/QUI\/50006\/2020"],"award-info":[{"award-number":["UID\/QUI\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BTM-MAT\/28237\/2017"],"award-info":[{"award-number":["PTDC\/BTM-MAT\/28237\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-106099RB-C43\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["PID2019-106099RB-C43\/AEI\/10.13039\/501100011033"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Basque Government Industry and Education Departments under the ELKARTEK and PIBA","award":["PIBA-2018-06"],"award-info":[{"award-number":["PIBA-2018-06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Scaffolds play an essential role in the success of tissue engineering approaches. Their intrinsic properties are known to influence cellular processes such as adhesion, proliferation and differentiation. Hydrogel-based matrices are attractive scaffolds due to their high-water content resembling the native extracellular matrix. In addition, polymer-based magnetoelectric materials have demonstrated suitable bioactivity, allowing to provide magnetically and mechanically activated biophysical electrical stimuli capable of improving cellular processes. The present work reports on a responsive scaffold based on poly (L-lactic acid) (PLLA) microspheres and magnetic microsphere nanocomposites composed of PLLA and magnetostrictive cobalt ferrites (CoFe2O4), combined with a hydrogel matrix, which mimics the tissue\u2019s hydrated environment and acts as a support matrix. For cell proliferation evaluation, two different cell culture conditions (2D and 3D matrices) and two different strategies, static and dynamic culture, were applied in order to evaluate the influence of extracellular matrix-like confinement and the magnetoelectric\/magneto-mechanical effect on cellular behavior. MC3T3-E1 proliferation rate is increased under dynamic conditions, indicating the potential use of hydrogel matrices with remotely stimulated magnetostrictive biomaterials for bone tissue engineering.<\/jats:p>","DOI":"10.3390\/nano10122421","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T20:09:40Z","timestamp":1607026180000},"page":"2421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Biodegradable Hydrogels Loaded with Magnetically Responsive Microspheres as 2D and 3D Scaffolds"],"prefix":"10.3390","volume":"10","author":[{"given":"Estela O.","family":"Carvalho","sequence":"first","affiliation":[{"name":"Centre of Physics, University of Minho, 4710-057 Braga, Portugal"},{"name":"Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9120-4847","authenticated-orcid":false,"given":"Clarisse","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Centre of Physics, University of Minho, 4710-057 Braga, Portugal"},{"name":"Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3118-4717","authenticated-orcid":false,"given":"Daniela M.","family":"Correia","sequence":"additional","affiliation":[{"name":"Centre of Physics, University of Minho, 4710-057 Braga, Portugal"},{"name":"Departamento de Qu\u00edmica e CQ-VR, Universidade de Tr\u00e1s-os-Montes e Alto Douro, 5001-801 Vila Real, Portugal"}]},{"given":"Gabriela","family":"Botelho","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica, Universidade do Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6791-7620","authenticated-orcid":false,"given":"Senentxu","family":"Lanceros-Mendez","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":[[2020,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bone.2018.07.012","article-title":"Impact of aging on bone, marrow and their interactions","volume":"119","author":"Hoffman","year":"2019","journal-title":"Bone"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1038\/s41598-018-24892-0","article-title":"Combining electrical stimulation and tissue engineering to treat large bone defects in a rat model","volume":"8","author":"Leppik","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"216","DOI":"10.4248\/BR201303002","article-title":"Bone regeneration based on tissue engineering conceptions-a 21st Century perspective","volume":"1","author":"Henkel","year":"2013","journal-title":"Bone Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1021\/acsabm.9b00020","article-title":"Tuning myoblast and preosteoblast cell adhesion site, orientation, and elongation through electroactive micropatterned scaffolds","volume":"2","author":"Cardoso","year":"2019","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Dimitriou, R., Jones, E., McGonagle, D., and Giannoudis, P.V. (2011). Bone regeneration: Current concepts and future directions. BMC Med., 9.","DOI":"10.1186\/1741-7015-9-66"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/nprot.2017.157","article-title":"Electroactive poly(vinylidene fluoride)-based structures for advanced applications","volume":"13","author":"Ribeiro","year":"2018","journal-title":"Nat. Protoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/elsc.201400144","article-title":"Piezoelectric poly(vinylidene fluoride) microstructure and poling state in active tissue engineering","volume":"15","author":"Ribeiro","year":"2015","journal-title":"Eng. Life Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nmat2614","article-title":"Emerging applications of stimuli-responsive polymer materials","volume":"9","author":"Stuart","year":"2010","journal-title":"Nat. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17014","DOI":"10.1038\/boneres.2017.14","article-title":"Injectable hydrogels for cartilage and bone tissue engineering","volume":"5","author":"Liu","year":"2017","journal-title":"Bone Res."},{"key":"ref_10","first-page":"1","article-title":"Bisphosphonate nanoclay edge-site interactions facilitate hydrogel self-assembly and sustained growth factor localization","volume":"11","author":"Kim","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.colsurfb.2019.06.023","article-title":"Hydrogel-based magnetoelectric microenvironments for tissue stimulation","volume":"181","author":"Hermenegildo","year":"2019","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rapino, M., Di Valerio, V., Zara, S., Gallorini, M., Marconi, G.D., Sancilio, S., Marsich, E., Ghinassi, B., Di Giacomo, V., and Cataldi, A. (2019). Chitlac-coated thermosets enhance osteogenesis and angiogenesis in a co-culture of dental pulp stem cells and endothelial cells. Nanomaterials, 9.","DOI":"10.3390\/nano9070928"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/nmat4051","article-title":"Interplay of matrix stiffness and protein tethering in stem cell differentiation","volume":"13","author":"Wen","year":"2014","journal-title":"Nat. Mater."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/nm.3464","article-title":"Rejuvenation of the muscle stem cell population restores strength to injured aged muscles","volume":"20","author":"Cosgrove","year":"2014","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/ncomms1792","article-title":"Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics","volume":"3","author":"Guvendiren","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1152\/physiol.00036.2016","article-title":"Modeling physiological events in 2D vs. 3D cell culture","volume":"32","author":"Duval","year":"2017","journal-title":"Physiology"},{"key":"ref_17","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":"Karahaliloglu","year":"2017","journal-title":"J. Bioact. Compat. Polym."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.colsurfb.2015.12.055","article-title":"Proving the suitability of magnetoelectric stimuli for tissue engineering applications","volume":"140","author":"Ribeiro","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"118","DOI":"10.5796\/electrochemistry.67.118","article-title":"Electrically Stimulated Modulation of Cellular Function in Proliferation, Differentiation, and Gene Expression","volume":"67","author":"Aizawa","year":"1999","journal-title":"Electrochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"45265","DOI":"10.1021\/acsami.9b14001","article-title":"Bioinspired Three-Dimensional Magnetoactive Scaffolds for Bone Tissue Engineering","volume":"11","author":"Fernandes","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.colsurfb.2015.08.043","article-title":"Piezoelectric polymers as biomaterials for tissue engineering applications","volume":"136","author":"Ribeiro","year":"2015","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.msec.2018.07.044","article-title":"Electroactive biomaterial surface engineering effects on muscle cells differentiation","volume":"92","author":"Ribeiro","year":"2018","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zheng, T., Yue, Z., Wallace, G.G., Du, Y., and Higgins, M.J. (2020). Nanoscale piezoelectric effect of biodegradable PLA-based composite fibers by piezoresponse force microscopy. Nanotechnology, 31.","DOI":"10.1088\/1361-6528\/ab96e3"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jcis.2016.05.012","article-title":"Processing and size range separation of pristine and magnetic poly(l-lactic acid) based microspheres for biomedical applications","volume":"476","author":"Correia","year":"2016","journal-title":"J. Colloid Interface Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4294","DOI":"10.3390\/ijms12074294","article-title":"Controlled delivery of gentamicin using poly(3-hydroxybutyrate) microspheres","volume":"12","author":"Francis","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6520","DOI":"10.1021\/ma050739z","article-title":"Crystallization behavior of poly(L-lactic acid) nanocomposites: Nucleation and growth probed by infrared spectroscopy","volume":"38","author":"Krikorian","year":"2005","journal-title":"Macromolecules"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/1521-3900(200208)185:1<35::AID-MASY35>3.0.CO;2-F","article-title":"Influence of physical cross-links in amorphous PET on room temperature ageing","volume":"185","author":"Kiflie","year":"2002","journal-title":"Macromol. Symp."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6445","DOI":"10.1021\/ma0504668","article-title":"Structure, dispersibility, and crystallinity of poly(hydroxybutyrate)\/poly(L-lactic acid) blends studied by FT-IR microspectroscopy and differential scanning calorimetry","volume":"38","author":"Furukawa","year":"2005","journal-title":"Macromolecules"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5590","DOI":"10.1039\/C4AY01289E","article-title":"Attenuated total reflectance\/Fourier transform infrared (ATR\/FTIR) mapping coupled with principal component analysis for the study of in vitro degradation of porous polylactide\/hydroxyapatite composite material","volume":"6","author":"Jing","year":"2014","journal-title":"Anal. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1023\/A:1020200822435","article-title":"A literature review of poly(lactic acid)","volume":"9","author":"Garlotta","year":"2001","journal-title":"J. Polym. Environ."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2174\/157341311795542435","article-title":"Biocompatibility studies of functionalized CoFe2O4 magnetic nanoparticles","volume":"7","author":"Prabhakar","year":"2011","journal-title":"Curr. Nanosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.aquatox.2015.07.003","article-title":"An in vivo evaluation of acute toxicity of cobalt ferrite (CoFe2O4) nanoparticles in larval-embryo Zebrafish (Danio rerio)","volume":"166","author":"Ahmad","year":"2015","journal-title":"Aquat. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.addr.2010.02.001","article-title":"Therapeutic cell delivery and fate control in hydrogels and hydrogel hybrids","volume":"62","author":"Wang","year":"2010","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Varaprasad, K., Vimala, K., Raghavendra, G.M., Jayaramudu, T., Sadiku, E.R., and Ramam, K. (2015). Cell Encapsulation in Polymeric Self-Assembled Hydrogels. Nanotechnology Applications for Tissue Engineering, Elsevier.","DOI":"10.1016\/B978-0-323-32889-0.00010-8"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.biomaterials.2016.01.035","article-title":"Magnetic nanocomposite scaffolds combined with static magnetic field in the stimulation of osteoblastic differentiation and bone formation","volume":"85","author":"Yun","year":"2016","journal-title":"Biomaterials"}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/10\/12\/2421\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:41:18Z","timestamp":1760179278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/10\/12\/2421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,3]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["nano10122421"],"URL":"https:\/\/doi.org\/10.3390\/nano10122421","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,3]]}}}