{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:37:24Z","timestamp":1793176644137,"version":"4.5.0"},"reference-count":70,"publisher":"American Chemical Society (ACS)","issue":"42","license":[{"start":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:00:00Z","timestamp":1792195200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:00:00Z","timestamp":1792195200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:00:00Z","timestamp":1792195200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"name":"Blazer Foundation"},{"name":"National Institutes of Health (NIH)","award":["R01AR084468"],"award-info":[{"award-number":["R01AR084468"]}]},{"name":"National Institutes of Health (NIH)","award":["R56AR070181"],"award-info":[{"award-number":["R56AR070181"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Total hip replacement (THR) remains a widely performed orthopedic procedure; however, degradation of cobalt-chromium-molybdenum (CoCrMo) alloy components can release leachates containing metallic ions and nanoparticles into the body over time. These metal degradation products (DPs) have been associated with local and systemic toxicity to the vital organs, including potential cardiac complications. This study investigated the biological effects of CoCrMo particles (CoCrMo P), cobalt ions (Co2+), and chromium ions (Cr3+) on cardiac tissue through a combination of in vitro and in vivo approaches focused on three primary aims: (i) in vitro toxicity evaluation using H9C2 myoblasts under static, dynamic, and all-trans retinoic acid (ATRA)-induced cardiac-like conditions; (ii) assessment of functional and structural toxicity in iPSC-derived cardiomyocytes; and (iii) evaluation of particle deposition and inflammation in cardiac tissues of a mouse model treated with DPs. From our investigation, we observed the following: (i) In vitro testing revealed that metal degradation products induced dose- and time-dependent cytotoxicity in H9C2 cells, with CoCrMo particles consistently producing the most severe effects. Dynamic culturing intensified these outcomes, suggesting that fluid shear may exacerbate DP toxicity compared with static conditions. ATRA-treated H9C2 cells expressed cTnT, thereby enabling cardiomyocyte-relevant observations of damage. (ii) In iPSC-derived cardiomyocytes, CoCrMo particle exposure disrupted calcium handling and increased contraction frequency, with accompanying morphological deterioration. (iii) In vivo testing revealed that mice injected with CoCrMo particles showed increased CD3-positive T-cell infiltration and signs of particle deposition in cardiac tissue. These findings support the hypothesis that long-term exposure to metal degradation products may contribute to adverse cardiac effects, demanding further investigation into implant biocompatibility and systemic impact.<\/jats:p>","DOI":"10.1021\/acsami.6c12704","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:06:07Z","timestamp":1792249567000},"page":"57091-57104","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating the Potential Cardiac Toxicity of Implant-Derived Metal Ions and Particles Using H9C2 and Stem Cell Model"],"prefix":"10.1021","volume":"18","author":[{"given":"Edgar","family":"Lopez","sequence":"first","affiliation":[{"name":"University of Illinois College of Medicine Rockford , , , ,","place":["Rockford, Illinois, United States, 61107"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puranjay","family":"Gupta","sequence":"additional","affiliation":[{"name":"University of Illinois College of Medicine Rockford , , , ,","place":["Rockford, Illinois, United States, 61107"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemalatha","family":"Kanniyappan","sequence":"additional","affiliation":[{"name":"University of Illinois College of Medicine Rockford , , , ,","place":["Rockford, Illinois, United States, 61107"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gitika","family":"Thakur","sequence":"additional","affiliation":[{"name":"University of Illinois College of Medicine Rockford , , , ,","place":["Rockford, Illinois, United States, 61107"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Fazle","family":"Alam","sequence":"additional","affiliation":[{"name":"University of Illinois College of Medicine Rockford , , , ,","place":["Rockford, Illinois, United States, 61107"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0813-0355","authenticated-orcid":true,"given":"Mareeswari","family":"Paramasivan","sequence":"additional","affiliation":[{"name":"University of Illinois College of Medicine Rockford , , , ,","place":["Rockford, Illinois, United States, 61107"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Li","sequence":"additional","affiliation":[{"name":"University of Illinois College of Medicine Rockford , , , ,","place":["Rockford, Illinois, United States, 61107"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Clements-Jewery","sequence":"additional","affiliation":[{"name":"University of Illinois College of Medicine , , , ,","place":["Rockford, Illinois, United States, 61107"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-7938","authenticated-orcid":true,"given":"Mathew T.","family":"Mathew","sequence":"additional","affiliation":[{"name":"University of Illinois College of Medicine Rockford , , , ,","place":["Rockford, Illinois, United States, 61107"]},{"name":"University of Illinois Chicago , , ,","place":["Chicago, Illinois, United States, 60612"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,17]]},"reference":[{"key":"2026102801064852200_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.artd.2023.101152","article-title":"Projections and Epidemiology of Revision Hip and Knee Arthroplasty in the United States to 2040-2060","volume":"21","author":"Shichman","year":"2040","journal-title":"Arthroplast. Today"},{"issue":"1","key":"2026102801064852200_cit2","doi-asserted-by":"publisher","first-page":"VII","DOI":"10.1590\/0100-3984.2020.53.1e2","article-title":"Hip Arthroplasty: Current Concepts and Potential Complications","volume":"53","author":"Serfaty","year":"2020","journal-title":"Radiol. Bras."},{"issue":"2","key":"2026102801064852200_cit3","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.ST.18.00078","article-title":"Direct Superior Approach to the Hip for Total Hip Arthroplasty","volume":"9","author":"Barrett","year":"2019","journal-title":"JBJS Essent. Surg. Tech."},{"key":"2026102801064852200_cit4","volume-title":"StatPearls","author":"Varacallo","year":"2023"},{"issue":"2","key":"2026102801064852200_cit5","doi-asserted-by":"publisher","first-page":"232","DOI":"10.26502\/josm.511500106","article-title":"Surgical Approaches in Total Hip Arthroplasty","volume":"5","author":"Supra","year":"2023","journal-title":"J. Orthop. Sports Med."},{"key":"2026102801064852200_cit6","article-title":"Hip Replacement Surgery","author":"Branch , N. S. C. and O","journal-title":"National Institute of Arthritis and Musculoskeletal and Skin Diseases"},{"issue":"6","key":"2026102801064852200_cit7","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1001\/jama.2020.22171","article-title":"Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review","volume":"325","author":"Katz","year":"2021","journal-title":"JAMA"},{"issue":"1","key":"2026102801064852200_cit8","first-page":"95","article-title":"Osteoarthritis of the Hip: An Overview","volume":"117","author":"Jotanovi\u0107","year":"2015","journal-title":"Period. Biol."},{"issue":"11","key":"2026102801064852200_cit9","doi-asserted-by":"publisher","DOI":"10.5435\/JAAOSGlobal-D-21-00014","article-title":"A Comparison of Risks and Benefits Regarding Hip Arthroplasty Fixation","volume":"5","author":"Matthias","year":"2021","journal-title":"JAAOS Glob. Res. Rev."},{"issue":"43","key":"2026102801064852200_cit10","doi-asserted-by":"publisher","first-page":"730","DOI":"10.3238\/arztebl.m2021.0323","article-title":"Total Hip Replacement for Osteoarthritis\u2014 Evidence-Based and Patient-Oriented Indications","volume":"118","author":"G\u00fcnther","year":"2021","journal-title":"Dtsch. Arztebl. Int."},{"issue":"15","key":"2026102801064852200_cit11","doi-asserted-by":"publisher","first-page":"3278","DOI":"10.3390\/polym15153278","article-title":"Updates on Biomaterials Used in Total Hip Arthroplasty (THA)","volume":"15","author":"Savin","year":"2023","journal-title":"Polymers"},{"key":"2026102801064852200_cit12","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1097\/01.blo.0000096810.78689.62","article-title":"Metal Degradation Products: A Cause for Concern in Metal-Metal Bearings?","volume":"417","author":"Jacobs","year":"2003","journal-title":"Clin. Orthop. Relat. Res."},{"issue":"3","key":"2026102801064852200_cit13","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.nano.2018.01.001","article-title":"Systemic and Local Toxicity of Metal Debris Released from Hip Prostheses: A Review of Experimental Approaches","volume":"14","author":"Bijukumar","year":"2018","journal-title":"Nanomedicine"},{"issue":"1","key":"2026102801064852200_cit14","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3390\/ma11010030","article-title":"Tribochemical Characterization and Tribocorrosive Behavior of CoCrMo Alloys: A Review","volume":"11","author":"Toh","year":"2017","journal-title":"Materials"},{"issue":"1","key":"2026102801064852200_cit15","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.rdc.2006.12.008","article-title":"Total Joint Arthroplasties: Current Concepts of Patient Outcomes after Surgery","volume":"33","author":"Jones","year":"2007","journal-title":"Rheum. Dis. Clin. North Am."},{"issue":"4","key":"2026102801064852200_cit16","doi-asserted-by":"publisher","first-page":"644","DOI":"10.3390\/cmd4040033","article-title":"Review on Corrosion, Tribocorrosion and Osseointegration of Titanium Alloys as Biomaterials","volume":"4","author":"Takadoum","year":"2023","journal-title":"Corros. Mater. Degrad."},{"key":"2026102801064852200_cit17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2024.106449","article-title":"Investigation of Cell-Accelerated Corrosion (CAC) on the CoCrMo Alloy with Segregation Banding: Hip Implant Applications","volume":"152","author":"Kanniyappan","year":"2024","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"2026102801064852200_cit18","doi-asserted-by":"crossref","unstructured":"Gilbert, J. L.\n          \n          2.4.3 - Metallic Degradation and the Biological Environment. In Biomaterials Science (Fourth Edition); Wagner, W. R., Sakiyama-Elbert, S. E., Zhang, G., Yaszemski, M. J., Eds.; Academic Press, 2020; pp 941\u2013954 10.1016\/B978-0-12-816137-1.00063-5.","DOI":"10.1016\/B978-0-12-816137-1.00063-5"},{"issue":"3","key":"2026102801064852200_cit19","doi-asserted-by":"publisher","first-page":"407","DOI":"10.3390\/ma12030407","article-title":"Corrosion of Metallic Biomaterials: A Review","volume":"12","author":"Eliaz","year":"2019","journal-title":"Materials"},{"issue":"2","key":"2026102801064852200_cit20","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s40496-022-00306-z","article-title":"Insight Into Corrosion of Dental Implants: From Biochemical Mechanisms to Designing Corrosion-Resistant Materials","volume":"9","author":"Nagay","year":"2022","journal-title":"Curr. Oral Health Rep."},{"key":"2026102801064852200_cit21","unstructured":"\u015awi\u0105tkowska, I.\n          Toxicity of Metal Debris From Hip Implants\n          University College London\n          https:\/\/discovery.ucl.ac.uk\/id\/eprint\/10085349\/1\/ILONA_SWIATKOWSKA_BLANK_FINAL_THESIS.pdf."},{"key":"2026102801064852200_cit22","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.toxlet.2021.07.004","article-title":"Systemic Toxicity Eliciting Metal Ion Levels from Metallic Implants and Orthopedic Devices \u2013 A Mini Review","volume":"350","author":"Badhe","year":"2021","journal-title":"Toxicol. Lett."},{"key":"2026102801064852200_cit23","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbiosy.2025.100113","article-title":"Evaluating the Potential Hepatotoxicity from Hip Implant Wear Products\u2014An in-Vitro and in-Vivo Study","volume":"18","author":"Thakur","year":"2025","journal-title":"Biomater. Biosyst."},{"issue":"8","key":"2026102801064852200_cit24","doi-asserted-by":"publisher","first-page":"392","DOI":"10.3390\/jfb14080392","article-title":"Corrosion Products from Metallic Implants Induce ROS and Cell Death in Human Motoneurons In Vitro","volume":"14","author":"Gla\u00df","year":"2023","journal-title":"J. Funct. Biomater."},{"key":"2026102801064852200_cit25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2025.161358","article-title":"Potential Pulmonary Toxicity Risks of Metal Products from Hip Implants: Using A549 Lung Cell and Animal Model","volume":"509","author":"Konety","year":"2025","journal-title":"Chem. Eng. J."},{"issue":"0","key":"2026102801064852200_cit26","doi-asserted-by":"publisher","first-page":"5","DOI":"10.21037\/aoj.2019.10.01","article-title":"Local and Systemic Consequences of Metal-on-Metal Hip Resurfacing Implants","volume":"5","author":"Campbell","year":"2020","journal-title":"Ann. Joint"},{"issue":"5","key":"2026102801064852200_cit27","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1042\/CS20130338","article-title":"Orthopaedic Implant Failure: Aseptic Implant Loosening\u2013the Contribution and Future Challenges of Mouse Models in Translational Research","volume":"127","author":"Cordova","year":"2014","journal-title":"Clin. Sci."},{"issue":"5","key":"2026102801064852200_cit28","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1302\/2046-3758.55.BJR-2016-0086","article-title":"The Pathobiology and Pathology of Aseptic Implant Failure","volume":"5","author":"Athanasou","year":"2016","journal-title":"Bone Joint Res."},{"key":"2026102801064852200_cit29","article-title":"Metal-on-Metal Hip Implants: The FDA\u2019s Activities FDA","author":"Health, C. for D. and R.","year":"2023"},{"key":"2026102801064852200_cit30","doi-asserted-by":"publisher","first-page":"241","DOI":"10.2174\/1874325001610010241","article-title":"Particle Disease: A Current Review of the Biological Mechanisms in Periprosthetic Osteolysis After Hip Arthroplasty","volume":"10","author":"Sukur","year":"2016","journal-title":"Open Orthop. J."},{"issue":"3","key":"2026102801064852200_cit31","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.artd.2017.01.005","article-title":"Cardiac Transplant Due to Metal Toxicity Associated with Hip Arthroplasty","volume":"3","author":"Moniz","year":"2017","journal-title":"Arthroplasty Today"},{"issue":"16","key":"2026102801064852200_cit32","doi-asserted-by":"publisher","first-page":"326","DOI":"10.21037\/atm.2017.06.27","article-title":"The Role of Reactive Oxygen Species in the Pathophysiology of Cardiovascular Diseases and the Clinical Significance of Myocardial Redox","volume":"5","author":"Moris","year":"2017","journal-title":"Ann. Transl. Med."},{"issue":"2","key":"2026102801064852200_cit33","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.jacc.2017.05.035","article-title":"Impact of Oxidative Stress on the Heart and Vasculature: Part 2 of a 3-Part Series","volume":"70","author":"M\u00fcnzel","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"2026102801064852200_cit34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.115784","article-title":"Patulin Induces ROS-Dependent Cardiac Cell Toxicity by Inducing DNA Damage and Activating Endoplasmic Reticulum Stress Apoptotic Pathway","volume":"269","author":"Zhang","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"2026102801064852200_cit35","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1308217","article-title":"iPSC-Cardiomyocytes in the Preclinical Prediction of Candidate Pharmaceutical Toxicity","volume":"15","author":"Lee","year":"2024","journal-title":"Front. Pharmacol."},{"issue":"1","key":"2026102801064852200_cit36","doi-asserted-by":"publisher","first-page":"5929","DOI":"10.1038\/s41467-024-50224-0","article-title":"Efficient and Reproducible Generation of Human iPSC-Derived Cardiomyocytes and Cardiac Organoids in Stirred Suspension Systems","volume":"15","author":"Prondzynski","year":"2024","journal-title":"Nat. Commun."},{"issue":"2","key":"2026102801064852200_cit37","doi-asserted-by":"publisher","first-page":"237","DOI":"10.3390\/bioengineering10020237","article-title":"The Exciting Realities and Possibilities of iPS-Derived Cardiomyocytes","volume":"10","author":"Takahashi","year":"2023","journal-title":"Bioengineering"},{"issue":"16","key":"2026102801064852200_cit38","doi-asserted-by":"publisher","first-page":"3871","DOI":"10.1113\/JP282562","article-title":"Advances in Induced Pluripotent Stem Cell-Derived Cardiac Myocytes: Technological Breakthroughs, Key Discoveries and New Applications","volume":"602","author":"Clancy","year":"2024","journal-title":"J. Physiol."},{"issue":"12","key":"2026102801064852200_cit39","doi-asserted-by":"publisher","first-page":"4829","DOI":"10.1002\/bit.27946","article-title":"Dynamic Microfluidic Bioreactor-Hip Simulator (DMBH) System for Implant Toxicity Monitoring","volume":"118","author":"Badhe","year":"2021","journal-title":"Biotechnol. Bioeng."},{"issue":"9","key":"2026102801064852200_cit40","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1080\/17435390.2018.1498929","article-title":"Differential Toxicity of Processed and Non-Processed States of CoCrMo Degradation Products Generated from a Hip Simulator on Neural Cells","volume":"12","author":"Bijukumar","year":"2018","journal-title":"Nanotoxicology"},{"issue":"5","key":"2026102801064852200_cit41","doi-asserted-by":"publisher","DOI":"10.1088\/1748-605X\/ad5ba9","article-title":"Harnessing Extracellular Vesicles-Mediated Signaling for Enhanced Bone Regeneration: Novel Insights into Scaffold Design","volume":"19","author":"Kanniyappan","year":"2024","journal-title":"Biomed. Mater."},{"key":"2026102801064852200_cit42","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.toxlet.2024.10.009","article-title":"Toxicity Risk from Hip Implant CoCrMo Particles: The Impact of Dynamic Flow Rate on Neuronal Cells in Microfluidic Systems","volume":"402","author":"Jeffers","year":"2024","journal-title":"Toxicol. Lett."},{"issue":"12","key":"2026102801064852200_cit43","doi-asserted-by":"publisher","first-page":"4829","DOI":"10.1002\/bit.27946","article-title":"Dynamic Microfluidic Bioreactor\u2014Hip Simulator (DMBH) System for Implant Toxicity Monitoring","volume":"118","author":"Badhe","year":"2021","journal-title":"Biotechnol. Bioeng."},{"issue":"1","key":"2026102801064852200_cit44","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/nprot.2012.150","article-title":"Directed Cardiomyocyte Differentiation from Human Pluripotent Stem Cells by Modulating Wnt\/\u03b2-Catenin Signaling under Fully Defined Conditions","volume":"8","author":"Lian","year":"2013","journal-title":"Nat. Protoc."},{"issue":"8","key":"2026102801064852200_cit45","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1080\/17435390.2024.2438118","article-title":"CoCrMo Nanoparticle Induces Neurotoxicity Mediated via Mitochondrial Dysfunction: A Study Model for Implant Derived Nanoparticle Effects","volume":"18","author":"Vijayakumar","year":"2024","journal-title":"Nanotoxicology"},{"key":"2026102801064852200_cit46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12989-020-00396-6","article-title":"Cobalt Oxide Nanoparticles Induce Oxidative Stress and Alter Electromechanical Function in Rat Ventricular Myocytes","volume":"18","author":"Savi","year":"2021","journal-title":"Part. Fibre Toxicol."},{"issue":"1","key":"2026102801064852200_cit47","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.apsb.2024.10.004","article-title":"Oxidative Stress and Inflammation in the Pathogenesis of Neurological Disorders: Mechanisms and Implications","volume":"15","author":"Dash","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"issue":"1","key":"2026102801064852200_cit48","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41420-024-02278-8","article-title":"Free Radicals and Their Impact on Health and Antioxidant Defenses: A Review","volume":"11","author":"Chandimali","year":"2025","journal-title":"Cell Death Discovery"},{"key":"2026102801064852200_cit49","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1186\/s13287-023-03596-x","article-title":"COX6A2 Deficiency Leads to Cardiac Remodeling in Human Pluripotent Stem Cell-Derived Cardiomyocytes","volume":"14","author":"Jiang","year":"2023","journal-title":"Stem Cell Res. Ther."},{"issue":"12","key":"2026102801064852200_cit50","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1038\/s41419-024-07302-4","article-title":"FXR-Regulated COX6A2 Triggers Mitochondrial Apoptosis of Pancreatic \u03b2-Cell in Type 2 Diabetes","volume":"15","author":"Shao","year":"2024","journal-title":"Cell Death Dis."},{"issue":"1","key":"2026102801064852200_cit51","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1186\/s11671-018-2728-6","article-title":"Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles","volume":"13","author":"Foroozandeh","year":"2018","journal-title":"Nanoscale Res. Lett."},{"issue":"4","key":"2026102801064852200_cit52","doi-asserted-by":"publisher","first-page":"551","DOI":"10.3892\/etm.2012.656","article-title":"Genotoxicity and Carcinogenicity of Cobalt-, Nickel- and Copper-Based Nanoparticles","volume":"4","author":"Magaye","year":"2012","journal-title":"Exp. Ther. Med."},{"issue":"17","key":"2026102801064852200_cit53","doi-asserted-by":"publisher","first-page":"16517","DOI":"10.1021\/acsnano.3c01124","article-title":"Rapid Internalization of Nanoparticles by Human Cells at the Single Particle Level","volume":"17","author":"Richards","year":"2023","journal-title":"ACS Nano"},{"key":"2026102801064852200_cit54","doi-asserted-by":"publisher","first-page":"2023-06","DOI":"10.1101\/2023.06.29.547038","article-title":"Nanoparticle Endocytosis Is Driven by Monocyte Phenotype Rather than Nanoparticle Size under High Shear Flow Conditions","author":"Aldarondo","year":"2023","journal-title":"bioRxiv"},{"issue":"10","key":"2026102801064852200_cit55","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12414","article-title":"Low Fluid Shear Stress Stimulates the Uptake of Noxious Endothelial Extracellular Vesicles via MCAM and PECAM-1 Cell Adhesion Molecules","volume":"13","author":"Coly","year":"2024","journal-title":"J. Extracell. Vesicles"},{"issue":"7","key":"2026102801064852200_cit56","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.3390\/cancers12071916","article-title":"Effect of Flow-Induced Shear Stress in Nanomaterial Uptake by Cells: Focus on Targeted Anti-Cancer Therapy","volume":"12","author":"ShurbajiAnlarHusseinElzatahryYalcin","year":"2020","journal-title":"Cancers"},{"key":"2026102801064852200_cit57","doi-asserted-by":"publisher","DOI":"10.1093\/rb\/rbad047","article-title":"Shear Stress Regulation of Nanoparticle Uptake in Vascular Endothelial Cells","volume":"10","author":"Zhang","year":"2023","journal-title":"Regener. Biomater."},{"key":"2026102801064852200_cit58","doi-asserted-by":"publisher","DOI":"10.3389\/fnano.2024.1496230","article-title":"Influence of Physicochemical Factors on the Interaction of Metallic Nanoparticles with Immune System Cells","volume":"6","author":"Guti\u00e9rrez-Cruz","year":"2025","journal-title":"Front. Nanotechnol."},{"key":"2026102801064852200_cit59","doi-asserted-by":"publisher","first-page":"102320","DOI":"10.1016\/j.mtbio.2025.102320","article-title":"Recent Advances in Metal Ions Overloading for Tumors: Mechanisms, Nanomaterials, and Therapies","volume":"35","author":"Gong","year":"2025","journal-title":"Mater. Today Bio"},{"issue":"3","key":"2026102801064852200_cit60","doi-asserted-by":"publisher","first-page":"703","DOI":"10.3390\/antiox12030703","article-title":"Metal-Based Nanoparticles and Their Relevant Consequences on Cytotoxicity Cascade and Induced Oxidative Stress","volume":"12","author":"Min","year":"2023","journal-title":"Antioxidants"},{"key":"2026102801064852200_cit61","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101729","article-title":"The Functional Significance of Redox-Mediated Intersubunit Cross-Linking in Regulation of Human Type 2 Ryanodine Receptor","volume":"37","author":"Nikolaienko","year":"2020","journal-title":"Redox Biol."},{"issue":"4","key":"2026102801064852200_cit62","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-020-0797-z","article-title":"Increased RyR2 Activity Is Exacerbated by Calcium Leak-Induced Mitochondrial ROS","volume":"115","author":"Hamilton","year":"2020","journal-title":"Basic Res. Cardiol."},{"issue":"1","key":"2026102801064852200_cit63","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/0003-9861(90)90548-D","article-title":"The Heavy Metal Ions Ag+ and Hg2+ Trigger Calcium Release from Cardiac Sarcoplasmic Reticulum","volume":"277","author":"Prabhu","year":"1990","journal-title":"Arch. Biochem. Biophys."},{"issue":"6","key":"2026102801064852200_cit64","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2023.119490","article-title":"Ionic Displacement of Ca2+ by Pb2+ in Calmodulin Is Affected by Arrhythmia-Associated Mutations","volume":"1870","author":"Marino","year":"2023","journal-title":"Biochim. Biophys. Acta, Mol. Cell Res."},{"key":"2026102801064852200_cit65","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.redox.2015.08.010","article-title":"Calcium and ROS: A Mutual Interplay","volume":"6","author":"G\u00f6rlach","year":"2015","journal-title":"Redox Biol."},{"key":"2026102801064852200_cit66","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9324018","article-title":"Crosstalk between Calcium and ROS in Pathophysiological Conditions","volume":"2019","author":"Feno","year":"2019","journal-title":"Oxid. Med. Cell. Longevity"},{"key":"2026102801064852200_cit67","doi-asserted-by":"publisher","first-page":"161","DOI":"10.4274\/haseki.3296","article-title":"A Rare Complication of Arthroplasty: Metallosis","volume":"55","author":"I\u015f\u0131k","journal-title":"Haseki Tip Bulteni"},{"issue":"9","key":"2026102801064852200_cit68","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1007\/s11999-010-1372-y","article-title":"Histological Features of Pseudotumor-like Tissues From Metal-on-Metal Hips","volume":"468","author":"Campbell","year":"2010","journal-title":"Clin. Orthop. Relat. Res."},{"issue":"4","key":"2026102801064852200_cit69","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.fjmd.2013.06.004","article-title":"Pseudotumor Formation Following Large-Diameter Metal-on-Metal Total Hip Arthroplasty\u2014Report of Two Cases and Literature Review","volume":"4","author":"Shih","year":"2013","journal-title":"Formos. J. Musculoskelet. Disord."},{"issue":"2","key":"2026102801064852200_cit70","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1002\/jor.25040","article-title":"Semi-quantitative Histology Confirms That the Macrophage Is the Predominant Cell Type in Metal-on-metal Hip Tissues","volume":"40","author":"Campbell","year":"2022","journal-title":"J. Orthop. Res."}],"container-title":["ACS Applied Materials &amp; Interfaces"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsami.6c12704","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aamick\/article-pdf\/doi\/10.1021\/acsami.6c12704\/68896273\/am-2026-127048.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aamick\/article-pdf\/doi\/10.1021\/acsami.6c12704\/68896273\/am-2026-127048.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T08:11:51Z","timestamp":1793175111000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aamick\/article\/18\/42\/57091\/5453278\/Evaluating-the-Potential-Cardiac-Toxicity-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,17]]},"references-count":70,"journal-issue":{"issue":"42","published-online":{"date-parts":[[2026,10,17]]},"published-print":{"date-parts":[[2026,10,28]]}},"URL":"https:\/\/doi.org\/10.1021\/acsami.6c12704","relation":{},"ISSN":["1944-8244","1944-8252"],"issn-type":[{"value":"1944-8244","type":"print"},{"value":"1944-8252","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,17]]}}}