{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:52:04Z","timestamp":1760143924713,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Great Ormond Street Hospital for Children Charity","award":["12SG15","17DS18","17DD46","ERC-2017-StG-757923"],"award-info":[{"award-number":["12SG15","17DS18","17DD46","ERC-2017-StG-757923"]}]},{"name":"NIHR Biomedical Research Centre Advanced Therapies for Structural Malformations and Tissue Damage pump-prime funding call","award":["12SG15","17DS18","17DD46","ERC-2017-StG-757923"],"award-info":[{"award-number":["12SG15","17DS18","17DD46","ERC-2017-StG-757923"]}]},{"name":"Great Ormond Street Hospital Charity Clinical Research Starter Grant","award":["12SG15","17DS18","17DD46","ERC-2017-StG-757923"],"award-info":[{"award-number":["12SG15","17DS18","17DD46","ERC-2017-StG-757923"]}]},{"name":"European Research Council","award":["12SG15","17DS18","17DD46","ERC-2017-StG-757923"],"award-info":[{"award-number":["12SG15","17DS18","17DD46","ERC-2017-StG-757923"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Spring-assisted surgery is a popular option for the treatment of non-syndromic craniosynostosis. The main drawback of this procedure is the need for a second surgery for spring removal, which could be avoided if a distractor material could be metabolised over time. Iron\u2013Manganese alloys (FeMn) have a good trade-off between degradation rate and strength; however, their biocompatibility is still debated. Materials and Methods: In this study, the neuro-compatibility of Fe-20Mn (wt.%) was assessed using standard assays. PC-12 cells were exposed to Fe-20Mn (wt.%) and stainless steel via indirect contact. To examine the cytotoxicity, a Cell Tox Green assay was carried out after 1, 2, and 3 days of incubation. Following differentiation, a neurite morphological examination after 1 and 7 days of incubation time was carried out. The degradation response in modified Hank\u2019s solution at 1, 3, and 7 days was investigated, too. Results: The cytotoxicity assay showed a higher toxicity of Fe-20Mn than stainless steel at earlier time points; however, at the latest time point, no differences were found. Neurite morphology was similar for cells exposed to Fe-20Mn and stainless steel. Conclusions: In conclusion, the Fe-20Mn alloy shows promising neuro-compatibility. Future studies will focus on in vivo studies to confirm the cellular response to Fe-20Mn.<\/jats:p>","DOI":"10.3390\/medicina60030440","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T08:59:37Z","timestamp":1709801977000},"page":"440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Vitro Assessment of the Neuro-Compatibility of Fe-20Mn as a Potential Bioresorbable Material for Craniofacial Surgery"],"prefix":"10.3390","volume":"60","author":[{"given":"Sara","family":"Ajami","sequence":"first","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Kraaneveld","sequence":"additional","affiliation":[{"name":"Erasmus Medical College, Erasmus University Rotterdam, 3015 CN Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten","family":"Koudstaal","sequence":"additional","affiliation":[{"name":"Oral Maxillo-Facial Surgery, Erasmus MC, 3015 CN Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Dunaway","sequence":"additional","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noor Ul Owase","family":"Jeelani","sequence":"additional","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Schievano","sequence":"additional","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-0038","authenticated-orcid":false,"given":"Chiara","family":"Bregoli","sequence":"additional","affiliation":[{"name":"National Research Council, Institute of Condensed Matter Chemistry and Technology for Energy, CNR ICMATE Unit of Lecco, 23900 Lecco, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7646-4595","authenticated-orcid":false,"given":"Jacopo","family":"Fiocchi","sequence":"additional","affiliation":[{"name":"National Research Council, Institute of Condensed Matter Chemistry and Technology for Energy, CNR ICMATE Unit of Lecco, 23900 Lecco, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5876-6007","authenticated-orcid":false,"given":"Carlo Alberto","family":"Biffi","sequence":"additional","affiliation":[{"name":"National Research Council, Institute of Condensed Matter Chemistry and Technology for Energy, CNR ICMATE Unit of Lecco, 23900 Lecco, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ausonio","family":"Tuissi","sequence":"additional","affiliation":[{"name":"National Research Council, Institute of Condensed Matter Chemistry and Technology for Energy, CNR ICMATE Unit of Lecco, 23900 Lecco, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1514-1979","authenticated-orcid":false,"given":"Alessandro","family":"Borghi","sequence":"additional","affiliation":[{"name":"UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK"},{"name":"Department of Engineering, Durham University, Durham DH1 3LE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.jcms.2016.07.007","article-title":"Increase of prevalence of craniosynostosis","volume":"44","author":"Cornelissen","year":"2016","journal-title":"J. Cranio-Maxillo-Facial Surg. Off. Publ. Eur. Assoc. Cranio-Maxillo-Facial Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.2147\/EB.S234075","article-title":"Neuro-Ophthalmological Manifestations of Craniosynostosis: Current Perspectives","volume":"13","author":"Duan","year":"2021","journal-title":"Eye Brain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/ejhg.2010.235","article-title":"Craniosynostosis","volume":"19","author":"Johnson","year":"2011","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"170e","DOI":"10.1097\/01.prs.0000304441.99483.97","article-title":"Cranial sutures: A brief review","volume":"121","author":"Slater","year":"2008","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1097\/SCS.0b013e3181ebcd27","article-title":"Intracranial and extracranial malformations in patients with craniofacial anomalies","volume":"21","author":"Alanay","year":"2010","journal-title":"J. Craniofacial Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e391","DOI":"10.1542\/peds.2009-3491","article-title":"Prevalence and complications of single-gene and chromosomal disorders in craniosynostosis","volume":"126","author":"Wilkie","year":"2010","journal-title":"Pediatrics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1002\/(SICI)1096-8628(19960329)62:3<282::AID-AJMG15>3.0.CO;2-G","article-title":"Genetic study of scaphocephaly","volume":"62","author":"Lajeunie","year":"1996","journal-title":"Am. J. Med. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1097\/SCS.0000000000003950","article-title":"Surgical Treatment of Nonsyndromic Craniosynostosis","volume":"28","author":"Klement","year":"2017","journal-title":"J. Craniofacial Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/scs.0b013e31815c94c8","article-title":"Spring-assisted cranioplasty vs pi-plasty for sagittal synostosis\u2014A long term follow-up study","volume":"19","author":"Windh","year":"2008","journal-title":"J. Craniofacial Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3189","DOI":"10.1007\/s00381-021-05330-5","article-title":"Spring-assisted posterior vault expansion-a single-centre experience of 200 cases","volume":"37","author":"Breakey","year":"2021","journal-title":"Child\u2019s Nerv. Syst. ChNS Off. J. Int. Soc. Pediatr. Neurosurg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/PRS.0000000000003465","article-title":"Spring-Assisted Cranioplasty for the Correction of Nonsyndromic Scaphocephaly: A Quantitative Analysis of 100 Consecutive Cases","volume":"140","author":"Rodgers","year":"2017","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1007\/s00381-012-1850-5","article-title":"Spring-assisted correction of sagittal suture synostosis","volume":"28","author":"Mathijssen","year":"2012","journal-title":"Child\u2019s Nerv. Syst. ChNS Off. J. Int. Soc. Pediatr. Neurosurg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1097\/SCS.0000000000001651","article-title":"Operative Management of Nonsyndromic Sagittal Synostosis: A Head-to-Head Meta-analysis of Outcomes Comparing 3 Techniques","volume":"26","author":"Gerety","year":"2015","journal-title":"J. Craniofacial Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/s00381-023-06221-7","article-title":"Posterior cranial vault distraction in children with syndromic craniosynostosis: The era of biodegradable materials-a comprehensive review of the literature and proposed novel global application","volume":"40","author":"Fouda","year":"2023","journal-title":"Child\u2019s Nerv. Syst. ChNS Off. J. Int. Soc. Pediatr. Neurosurg."},{"key":"ref_15","unstructured":"Heiden, M., Walker, E., and Stanciu, L. (2015). Magnesium, Iron and Zinc Alloys, the Trifecta of Bioresorbable Orthopaedic and Vascular Implantation\u2014A Review. J. Biotechnol. Biomater."},{"key":"ref_16","first-page":"4186","article-title":"Research status of biodegradable metals designed for oral and maxillofacial applications: A review","volume":"6","author":"Xia","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mser.2014.01.001","article-title":"Biodegradable metals","volume":"77","author":"Zheng","year":"2014","journal-title":"Mater. Sci. Eng. R Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1136\/heart.86.5.563","article-title":"A novel approach to temporary stenting: Degradable cardiovascular stents produced from corrodible metal-results 6-18 months after implantation into New Zealand white rabbits","volume":"86","author":"Peuster","year":"2001","journal-title":"Heart"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1016\/j.msec.2008.12.019","article-title":"Biocompatibility of pure iron: In vitro assessment of degradation kinetics and cytotoxicity on endothelial cells","volume":"29","author":"Zhu","year":"2009","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Carnicer-Lombarte, A., Chen, S.-T., Malliaras, G.G., and Barone, D.G. (2021). Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics. Front. Bioeng. Biotechnol., 9.","DOI":"10.3389\/fbioe.2021.622524"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1179\/174329008X284868","article-title":"Iron\u2013manganese: New class of metallic degradable biomaterials prepared by powder metallurgy","volume":"51","author":"Hermawan","year":"2008","journal-title":"Powder Metall."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jbm.a.32224","article-title":"Degradable metallic biomaterials: Design and development of Fe-Mn alloys for stents","volume":"93","author":"Hermawan","year":"2010","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1080\/10408390500466174","article-title":"The role of nutrients in bone health, from A to Z","volume":"46","author":"Palacios","year":"2006","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.taap.2007.03.001","article-title":"Manganese: Recent advances in understanding its transport and neurotoxicity","volume":"221","author":"Aschner","year":"2007","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1021\/acsbiomaterials.8b01497","article-title":"Exploring the Role of Manganese on the Microstructure, Mechanical Properties, Biodegradability, and Biocompatibility of Porous Iron-Based Scaffolds","volume":"5","author":"Dargusch","year":"2019","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1016\/j.actbio.2009.11.025","article-title":"Fe-Mn alloys for metallic biodegradable stents: Degradation and cell viability studies","volume":"6","author":"Hermawan","year":"2010","journal-title":"Acta Biomater."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.matlet.2010.10.068","article-title":"In vitro investigation of Fe30Mn6Si shape memory alloy as potential biodegradable metallic material","volume":"65","author":"Liu","year":"2011","journal-title":"Mater. Lett."},{"key":"ref_28","unstructured":"(2021). Standard Guide for Laboratory Immersion Corrosion Testing of Metals. Standard No. ASTM-G31."},{"key":"ref_29","unstructured":"(2009). Biological Evaluation of Medical Devices\u2014Part 5: Tests for In Vitro cytotoxicity. Standard No. ISO 10993-5."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.ntt.2004.02.006","article-title":"Assessment of PC12 cell differentiation and neurite growth: A comparison of morphological and neurochemical measures","volume":"26","author":"Das","year":"2004","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wiatrak, B., Kubis-Kubiak, A., Piwowar, A., and Barg, E. (2020). PC12 Cell Line: Cell Types, Coating of Culture Vessels, Differentiation and Other Culture Conditions. Cells, 9.","DOI":"10.3390\/cells9040958"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1021\/acsbiomaterials.1c00365","article-title":"Six-Month Long In Vitro Degradation Tests of Biodegradable Twinning-Induced Plasticity Steels Alloyed with Ag for Stent Applications","volume":"7","author":"Loffredo","year":"2021","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.matlet.2016.06.017","article-title":"CO2-rich atmosphere strongly affects the degradation of Fe-21Mn-1C for biodegradable metallic implants","volume":"181","author":"Mouzou","year":"2016","journal-title":"Mater. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"102250","DOI":"10.1016\/j.mtcomm.2021.102250","article-title":"Mechanical and degradation behavior of three Fe-Mn-C alloys for potential biomedical applications","volume":"27","author":"Gambaro","year":"2021","journal-title":"Mater. Today Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102447","DOI":"10.1016\/j.mtcomm.2021.102447","article-title":"The effect of Si addition and thermomechanical processing in an Fe-Mn alloy for biodegradable implants: Mechanical performance and degradation behavior","volume":"27","author":"Fiocchi","year":"2021","journal-title":"Mater. Today Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.jallcom.2018.07.206","article-title":"Design and characterization of nano and bimodal structured biodegradable Fe-Mn-Ag alloy with accelerated corrosion rate","volume":"767","author":"Khakbiz","year":"2018","journal-title":"J. Alloys Compd."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.matdes.2018.01.005","article-title":"S and B microalloying of biodegradable Fe-30Mn-1C\u2014Effects on microstructure, tensile properties, in vitro degradation and cytotoxicity","volume":"142","author":"Hufenbach","year":"2018","journal-title":"Mater. Des."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8593","DOI":"10.1016\/j.actbio.2013.04.016","article-title":"Novel processing of iron-manganese alloy-based biomaterials by inkjet 3-D printing","volume":"9","author":"Chou","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.msec.2012.11.002","article-title":"On the cytocompatibility of biodegradable Fe-based alloys","volume":"33","author":"Schinhammer","year":"2013","journal-title":"Mater. Sci. Engineering. C Mater. Biol. Appl."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Scarcello, E., Herpain, A., Tomatis, M., Turci, F., Jacques, P.J., and Lison, D. (2020). Hydroxyl radicals and oxidative stress: The dark side of Fe corrosion. Colloids Surfaces. B Biointerfaces, 185.","DOI":"10.1016\/j.colsurfb.2019.110542"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1002\/jbm.b.33234","article-title":"In vitro and in vivo corrosion properties of new iron-manganese alloys designed for cardiovascular applications","volume":"103","author":"Drynda","year":"2015","journal-title":"J. Biomed. Mater. Research. Part B Appl. Biomater."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1093\/toxsci\/kfn114","article-title":"Assessment of chemical effects on neurite outgrowth in PC12 cells using high content screening","volume":"105","author":"Radio","year":"2008","journal-title":"Toxicol. Sci. Off. J. Soc. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0166-4328(96)02251-6","article-title":"Behavioral consequences of abnormal cortical development: Insights into developmental disabilities","volume":"86","year":"1997","journal-title":"Behav. Brain Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0166-2236(00)02118-4","article-title":"Rho proteins, mental retardation and the cellular basis of cognition","volume":"25","author":"Ramakers","year":"2002","journal-title":"Trends Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.neuro.2008.02.011","article-title":"Developmental neurotoxicity testing in vitro: Models for assessing chemical effects on neurite outgrowth","volume":"29","author":"Radio","year":"2008","journal-title":"Neurotoxicology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Boulan, B., Beghin, A., Ravanello, C., Deloulme, J.-C., Gory-Faur\u00e9, S., Andrieux, A., Brocard, J., and Denarier, E. (2020). AutoNeuriteJ: An ImageJ plugin for measurement and classification of neuritic extensions. PLoS ONE, 15.","DOI":"10.1101\/2020.05.29.123000"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/3\/440\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:10:23Z","timestamp":1760105423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/3\/440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,7]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["medicina60030440"],"URL":"https:\/\/doi.org\/10.3390\/medicina60030440","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2024,3,7]]}}}