{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:20:07Z","timestamp":1780536007524,"version":"3.54.1"},"reference-count":50,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-093512-B-C21"],"award-info":[{"award-number":["RTI2018-093512-B-C21"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>Three-dimensional printing technologies have been recently proposed to monitor cell cultures and implement cell bioreactors for different biological applications. In tissue engineering, the control of tissue formation is crucial to form tissue constructs of clinical relevance, and 3D printing technologies can also play an important role for this purpose. In this work, we study 3D-printed sensors that have been recently used in cell culture and tissue engineering applications in biological laboratories, with a special focus on the technique of electrical impedance spectroscopy. Furthermore, we study new 3D-printed actuators used for the stimulation of stem cells cultures, which is of high importance in the process of tissue formation and regenerative medicine. Key challenges and open issues, such as the use of 3D printing techniques in implantable devices for regenerative medicine, are also discussed.<\/jats:p>","DOI":"10.3390\/s20195617","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T09:04:12Z","timestamp":1601543052000},"page":"5617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["3D-Printed Sensors and Actuators in Cell Culture and Tissue Engineering: Framework and Research Challenges"],"prefix":"10.3390","volume":"20","author":[{"given":"Pablo","family":"P\u00e9rez","sequence":"first","affiliation":[{"name":"Instituto de Microelectr\u00f3nica de Sevilla, IMSE-CNM (CSIC, Universidad de Sevilla), Av. Am\u00e9rico Vespucio, sn, 41092 Sevilla, Spain"},{"name":"Escuela T\u00e9cnica Superior de Ingenier\u00eda Inform\u00e1tica, Departamento de Tecnolog\u00eda Electr\u00f3nica, Universidad de Sevilla, Av. Reina Mercedes sn, 41012 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9881-0148","authenticated-orcid":false,"given":"Juan Alfonso","family":"Serrano","sequence":"additional","affiliation":[{"name":"Instituto de Microelectr\u00f3nica de Sevilla, IMSE-CNM (CSIC, Universidad de Sevilla), Av. Am\u00e9rico Vespucio, sn, 41092 Sevilla, Spain"},{"name":"Escuela T\u00e9cnica Superior de Ingenier\u00eda Inform\u00e1tica, Departamento de Tecnolog\u00eda Electr\u00f3nica, Universidad de Sevilla, Av. Reina Mercedes sn, 41012 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6388-4462","authenticated-orcid":false,"given":"Alberto","family":"Olmo","sequence":"additional","affiliation":[{"name":"Instituto de Microelectr\u00f3nica de Sevilla, IMSE-CNM (CSIC, Universidad de Sevilla), Av. Am\u00e9rico Vespucio, sn, 41092 Sevilla, Spain"},{"name":"Escuela T\u00e9cnica Superior de Ingenier\u00eda Inform\u00e1tica, Departamento de Tecnolog\u00eda Electr\u00f3nica, Universidad de Sevilla, Av. Reina Mercedes sn, 41012 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1089\/3dp.2017.0103","article-title":"3D-Printed Reusable Cell Culture Chamber with Integrated Electrodes for Electrical Stimulation and Parallel Microscopic Evaluation","volume":"5","author":"Schneidereit","year":"2018","journal-title":"3D Print. Addit. Manuf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1118\/1.1995712","article-title":"Electrical Impedance Tomography: Methods, History and Applications","volume":"32","author":"Djajaputra","year":"2005","journal-title":"Med. Phys."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.snb.2012.09.083","article-title":"Monitoring living cell assays with bio-impedance sensors","volume":"176","author":"Daza","year":"2013","journal-title":"Sens. Actuators B Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7896","DOI":"10.1073\/pnas.88.17.7896","article-title":"Micromotion of mammalian cells measured electrically","volume":"88","author":"Giaever","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.bios.2014.02.079","article-title":"Silicon nanograss based impedance biosensor for label free detection of rare metastatic cells among primary cancerous colon cells, suitable for more accurate cancer staging","volume":"59","author":"Abdolahad","year":"2014","journal-title":"Biosens. Bioelectron."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Olmo, A., Yuste, Y., Serrano, J.A., Maldonado-Jacobi, A., P\u00e9rez, P., Huertas, G., Pereira, S., Y\u00fafera, A., and De La Portilla, F. (2020). Electrical Modeling of the Growth and Differentiation of Skeletal Myoblasts Cell Cultures for Tissue Engineering. Sensors, 20.","DOI":"10.3390\/s20113152"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.bios.2012.01.013","article-title":"Electric impedance sensing in cell-substrates for rapid and selective multipotential differentiation capacity monitoring of human mesenchymal stem cells","volume":"34","author":"Reitinger","year":"2012","journal-title":"Biosens. Bioelectron."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhang, X., Wang, W., and Jang, S. (2018). The Modeling, Design, Fabrication, and Application of Biosensor Based on Electric Cell-Substrate Impedance Sensing (ECIS) Technique in Environmental Monitoring. Biosensors for Environmental Monitoring, Intechopen.","DOI":"10.5772\/intechopen.81178"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Xu, Y., Wu, X., Guo, X., Kong, B., Zhang, M., Qian, X., Mi, S., and Sun, W. (2017). The Boom in 3D-Printed Sensor Technology. Sensors, 17.","DOI":"10.3390\/s17051166"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.bios.2018.09.046","article-title":"3D cell-based biosensor for cell viability and drug assessment by 3D electric cell\/matrigel-substrate impedance sensing","volume":"130","author":"Pan","year":"2019","journal-title":"Biosens. Bioelectron."},{"key":"ref_11","unstructured":"Rodr\u00edguez, F. (2020). Dise\u00f1o de Biorreactores Para Cultivos Celulares Basados en Impresi\u00f3n 3D, Departamento de Tecnolog\u00eda Electr\u00f3nica, Universidad de Sevilla. Available online: http:\/\/institucional.us.es\/sinergia\/."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"012017","DOI":"10.1088\/1742-6596\/1272\/1\/012017","article-title":"PCB-3D-Printed, Reliable and Reusable Wells for Impedance Spectroscopy of Aqueous Solutions","volume":"1272","author":"Campo","year":"2019","journal-title":"J. Phys. Conf. Ser."},{"key":"ref_13","unstructured":"(2020, September 25). Applied Biophysics, USA. Available online: https:\/\/www.biophysics.com\/."},{"key":"ref_14","unstructured":"(2020, September 25). Roche Diagnostics, USA. Available online: https:\/\/diagnostics.roche.com\/."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1038\/s41467-020-15316-7","article-title":"3D printing of conducting polymers","volume":"11","author":"Yuk","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1557\/mrs.2011.270","article-title":"Selective laser sintering and its application in biomedical engineering","volume":"36","author":"Duan","year":"2011","journal-title":"MRS Bull."},{"key":"ref_17","unstructured":"Arum, H., Moss, E.Y., and Frazier, A.B. (2005, January 5\u20139). Whole cell electrical impedance spectroscopy for studying ion channel activity. Proceedings of the 13th International Conference on Solid-State Sensors, Actuators and Microsystems, Seoul, Korea. Digest of Technical Papers; TRANSDUCERS\u201805."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"45009","DOI":"10.1088\/1748-6041\/4\/4\/045009","article-title":"Toxicity evaluation of PEDOT\/biomolecular composites intended for neural communication electrodes","volume":"4","author":"Asplund","year":"2009","journal-title":"Biomed. Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"172001","DOI":"10.1088\/1361-6528\/ab5f29","article-title":"3D printed nanomaterial-based electronic, biomedical, and bioelectronic devices","volume":"31","author":"Hales","year":"2020","journal-title":"Nanotechnology"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gulyas, M., Csiszer, M., Mehes, E., and Czirok, A. (2018). Software tools for cell culture-related 3D printed structures. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0203203"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Han, T., Kundu, S., Nag, A., and Xu, Y. (2019). 3D Printed Sensors for Biomedical Applications: A Review. Sensors, 19.","DOI":"10.3390\/s19071706"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"041109","DOI":"10.1063\/1.5046087","article-title":"3D printing in cell culture systems and medical applications","volume":"5","author":"Lerman","year":"2018","journal-title":"Appl. Phys. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.snb.2015.07.017","article-title":"New perspectives in shake flask pH control using a 3D-printed control unit based on pH online measurement","volume":"221","author":"Ude","year":"2015","journal-title":"Sens. Actuators B Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1016\/j.msec.2017.02.094","article-title":"Metallic powder-bed based 3D printing of cellular scaffolds for orthopaedic implants: A state-of-the-art review on manufacturing, topological design, mechanical properties and biocompatibility","volume":"76","author":"Tan","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1039\/b201230h","article-title":"UV-induced DNA damage and repair: A review","volume":"1","author":"Sinha","year":"2002","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_26","unstructured":"Alzate, J.V., and Saavedra, S. (2020). Caracterizaci\u00f3n El\u00e9ctrica de un Cultivo Celular Utilizando Espectroscop\u00eda de Impedancia, Universidad Aut\u00f3noma de Occidente. Available online: http:\/\/red.uao.edu.co\/bitstream\/10614\/12417\/5\/T09268.pdf."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Joshi, K., and Esfandyarpour, R. (2020, January 5). An inkjet-printed and reusable platform for single cell impedance cytometry. Proceedings of the SPIE 11235, Microfluidics, BioMEMS, and Medical Microsystems XVIII, San Francisco, CA, USA.","DOI":"10.1117\/12.2543160"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.proeng.2016.11.218","article-title":"Preliminary Study of Inkjet Printed Sensors for Monitoring Cell Cultures","volume":"168","author":"Tonello","year":"2016","journal-title":"Procedia Eng."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Paivana, G., Apostolou, T., Mavrikou, S., Barmpakos, D., Kaltsas, G., and Kintzios, S. (2019). Impedance Study of Dopamine Effects after Application on 2D and 3D Neuroblastoma Cell Cultures Developed on a 3D-Printed Well. Chemosensors, 7.","DOI":"10.3390\/chemosensors7010006"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jneumeth.2015.05.001","article-title":"Low cost production of 3D-printed devices and electrostimulation chambers for the culture of primary neurons","volume":"251","author":"Wardyn","year":"2015","journal-title":"J. Neurosci. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2634","DOI":"10.1021\/nl4007744","article-title":"3D Printed Bionic Ears","volume":"13","author":"Mannoor","year":"2013","journal-title":"Nano Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1038\/ncomms4329","article-title":"3Dmultifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium","volume":"5","author":"Xu","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_33","first-page":"1265","article-title":"Electrical pulse stimulation of skeletal myoblasts cell cultures with simulated action potentials","volume":"13","author":"Villanueva","year":"2019","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/apha.12830","article-title":"Electrical pulse stimulation of cultured skeletal muscle cells as a model for in vitro exercise\u2014Possibilities and limitations","volume":"220","author":"Nikolic","year":"2017","journal-title":"Acta Physiol."},{"key":"ref_35","first-page":"1015","article-title":"Electrical stimulation-induced cell clustering in cultured neural networks","volume":"45","author":"Jun","year":"2007","journal-title":"Med. Boil. Eng."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1152\/japplphysiol.00855.2016","article-title":"Neuromuscular electrical stimulation improves skeletal muscle regeneration through satellite cell fusion with myofibers in healthy elderly subjects","volume":"123","author":"Mancinelli","year":"2017","journal-title":"J. Appl. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.bios.2017.11.039","article-title":"A novel 3D bioprinted flexible and biocompatible hydrogel bioelectronic platform","volume":"102","author":"Agarwala","year":"2018","journal-title":"Biosens. Bioelectron."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3957931","DOI":"10.1155\/2019\/3957931","article-title":"Application of 3D Printing Technology for Design and Manufacturing of Customized Components for a Mechanical Stretching Bioreactor","volume":"2019","author":"Putame","year":"2019","journal-title":"J. Healthc. Eng."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhou, Y. (2016). The Application of Ultrasound in 3D Bio-Printing. Molecules, 21.","DOI":"10.3390\/molecules21050590"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.bprint.2017.04.003","article-title":"Integrated 3D printed scaffolds and electrical stimulation for enhancing primary human cardiomyocyte cultures","volume":"6","author":"Adams","year":"2017","journal-title":"Bioprinting"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.msec.2019.03.047","article-title":"Engineered 3D printed poly(\u025b-caprolactone)\/graphene scaffolds for bone tissue engineering","volume":"100","author":"Wang","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Cheng, J., Chen, Y., Wu, J.-W., Ji, X., and Wu, S. (2019). 3D Printing of BaTiO3 Piezoelectric Ceramics for a Focused Ultrasonic Array. Sensors, 19.","DOI":"10.3390\/s19194078"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.nanoen.2019.02.073","article-title":"Self-powered implantable electrical stimulator for osteoblasts\u2019 proliferation and differentiation","volume":"59","author":"Tian","year":"2019","journal-title":"Nano Energy"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.protcy.2015.07.026","article-title":"3D Printed Biocompatible Enclosures for an Implantable DBS Microdevice","volume":"20","author":"Adams","year":"2015","journal-title":"Procedia Technol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sigurdsson, S.A., Yu, Z., Lee, J.-H., and Nurmikko, A.V. (2020). Method for Large Scale Implantation of 3D Microdevice Ensembles into Brain and Soft Tissue. bioRxiv.","DOI":"10.1101\/2020.03.06.979294"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/nmat4782","article-title":"Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing","volume":"16","author":"Lind","year":"2016","journal-title":"Nat. Mater."},{"key":"ref_47","first-page":"7167186","article-title":"Evaluation of Implanted Stent Occlusion Status Based on Neointimal Tissue Bioimpedance Simulations","volume":"2019","author":"Olmo","year":"2019","journal-title":"J. Sens."},{"key":"ref_48","unstructured":"P\u00e9rez, A. (2020). Estudio de Diferentes Tecnolog\u00edas de Fabricaci\u00f3n de Electrodos Para Stents Inteligentes, Departamento de Tecnolog\u00eda Electr\u00f3nica, Universidad de Sevilla."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Miguel, J.A., Lechuga, Y., and Mart\u00ednez, M. (2018). AFM-Based Characterization Method of Capacitive MEMS Pressure Sensors for Cardiological Applications. Micromachines, 9.","DOI":"10.3390\/mi9070342"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"eaba5575","DOI":"10.1126\/sciadv.aba5575","article-title":"3D printed deformable sensors","volume":"6","author":"Zhu","year":"2020","journal-title":"Sci. Adv."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/20\/19\/5617\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:15:36Z","timestamp":1760177736000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/20\/19\/5617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,1]]},"references-count":50,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["s20195617"],"URL":"https:\/\/doi.org\/10.3390\/s20195617","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,1]]}}}