{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:07:48Z","timestamp":1788772068180,"version":"build-2803163510"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"17","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Seoul National University Hospital Research Fund","award":["0320240300"],"award-info":[{"award-number":["0320240300"]}]},{"name":"National Research Foundation of Korea (NRF) grant, Korean government (MSIT)","award":["RS-2023-00213423"],"award-info":[{"award-number":["RS-2023-00213423"]}]},{"name":"Seoul Metropolitan Government?Seoul National University Boramae Medical Center Research Fund","award":["04-2023-0016"],"award-info":[{"award-number":["04-2023-0016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fibrotic encapsulation remains a major limitation of silicone-based soft-tissue implants and contributes to capsular contracture. Although biochemical and immunological factors have been extensively investigated, the contribution of implant stiffness to the peri-implant foreign body response remains incompletely defined. Here, we evaluated whether silicone implant stiffness is associated with fibrotic remodeling and changes in mechanotransductive signaling. Polydimethylsiloxane (PDMS) substrates and implants with elastic moduli ranging from 60 to 2000 kPa were fabricated and examined using human dermal fibroblasts and a rat subcutaneous implantation model. Increasing stiffness was associated with enhanced \u03b21 integrin expression, FAK phosphorylation, ROCK1 expression, actin cytoskeletal organization, nuclear YAP localization, and upregulation of profibrotic markers, including \u03b1-SMA, CTGF, COL1A1, and COL3A1. In vivo, stiffer implants showed greater capsule thickness, collagen deposition, inflammatory cell infiltration, MPO and TGF-\u03b21 expression, and sustained stiffness-associated changes in mechanotransductive proteins at 4 and 12 weeks. In contrast, the most compliant silicone condition attenuated these fibrosis-associated responses. These findings support material stiffness as a modifiable design parameter for silicone-based implantable biomaterials and suggest that relative softening within a feasible silicone material range may help reduce peri-implant fibrotic encapsulation.<\/jats:p>","DOI":"10.1021\/acsabm.6c01259","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:02:09Z","timestamp":1786687329000},"page":"8314-8329","source":"Crossref","is-referenced-by-count":0,"title":["Stiffness-Dependent Mechanotransductive Signaling in Silicone Implant-Associated Fibrotic Encapsulation"],"prefix":"10.1021","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0235-1261","authenticated-orcid":true,"given":"Jun Ho","family":"Park","sequence":"first","affiliation":[{"name":"Seoul National University College of Medicine, SMG-SNU Boramae Medical Center , , 20 Boramae-ro 5-gil , ,","place":["Dongjak-gu, Republic of Korea, 07061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine, SMG-SNU Boramae Medical Center , , 20 Boramae-ro 5-gil , ,","place":["Dongjak-gu, Republic of Korea, 07061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki-Myo","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine, SMG-SNU Boramae Medical Center , , 20 Boramae-ro 5-gil , ,","place":["Dongjak-gu, Republic of Korea, 07061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2498-1301","authenticated-orcid":true,"given":"Yan","family":"Lee","sequence":"additional","affiliation":[{"name":"Seoul National University , , 1 Gwanak-ro, Gwanak-gu , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Ung","family":"Park","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine, SMG-SNU Boramae Medical Center , , 20 Boramae-ro 5-gil , ,","place":["Dongjak-gu, Republic of Korea, 07061"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"2026090701074437400_cit1","doi-asserted-by":"publisher","first-page":"e29","DOI":"10.1016\/j.bjps.2018.05.022","article-title":"Risk Factors for Developing Capsular Contracture in Women after Breast Implant Surgery: A Systematic Review of the Literature","volume":"71","author":"Bachour","year":"2018","journal-title":"J. Plast. Reconstr. Aesthet. Surg."},{"key":"2026090701074437400_cit2","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1097\/PRS.0000000000003915","article-title":"Microbial Evaluation in Capsular Contracture of Breast Implants","volume":"141","author":"Galdiero","year":"2018","journal-title":"Plast. Reconstr. Surg."},{"key":"2026090701074437400_cit3","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.jpra.2017.10.007","article-title":"Low Rate of Capsular Contracture in a Series of 214 Consecutive Primary and Revision Breast Augmentations Using Microtextured Implants","volume":"15","author":"Tanner","year":"2018","journal-title":"JPRAS Open"},{"key":"2026090701074437400_cit4","doi-asserted-by":"publisher","DOI":"10.1097\/prs.0000000000010358","article-title":"Systematic Review of Capsular Contracture Management Following Breast Augmentation: An Update","volume":"153","author":"Boyd","year":"2024","journal-title":"Plast. Reconstr. Surg."},{"key":"2026090701074437400_cit5","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.bjps.2024.04.031","article-title":"Impact of Post-Operative Infection on Revision Procedures in Breast Reconstruction: A Marketscan Database Analysis","volume":"93","author":"Francis","year":"2024","journal-title":"J. Plast. Reconstr. Aesthet. Surg."},{"key":"2026090701074437400_cit6","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.bjps.2024.08.057","article-title":"Capsular Contracture in Breast Reconstruction: A Systematic Review and Meta-Analysis","volume":"98","author":"Christodoulou","year":"2024","journal-title":"J. Plast. Reconstr. Aesthet. Surg."},{"key":"2026090701074437400_cit7","doi-asserted-by":"publisher","first-page":"2714","DOI":"10.1007\/s00266-021-02473-3","article-title":"Histological Analyses of Capsular Contracture and Associated Risk Factors: A Systematic Review","volume":"45","author":"Larsen","year":"2021","journal-title":"Aesthet. Plast. Surg."},{"key":"2026090701074437400_cit8","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1055\/s-0041-1731793","article-title":"Current Concepts in Capsular Contracture: Pathophysiology, Prevention, and Management","volume":"35","author":"Safran","year":"2021","journal-title":"Semin. Plast. Surg."},{"key":"2026090701074437400_cit9","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1097\/PRS.0000000000010573","article-title":"Toward a Consensus Approach for Assessing Capsular Contracture Severity and Progression: A Systematic Review","volume":"153","author":"Mohan","year":"2024","journal-title":"Plast. Reconstr. Surg."},{"key":"2026090701074437400_cit10","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1038\/s41551-021-00722-z","article-title":"Suppression of the Fibrotic Encapsulation of Silicone Implants by Inhibiting the Mechanical Activation of Pro-Fibrotic TGF-\u03b2","volume":"5","author":"Noskovicova","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"2026090701074437400_cit11","doi-asserted-by":"publisher","DOI":"10.3390\/app12084056","article-title":"Reducing Capsular Contracture Formation in Breast Augmentation with Silicone Implants: Experimental Study on Rats","volume":"12","author":"Aladari","year":"2022","journal-title":"Appl. Sci."},{"key":"2026090701074437400_cit12","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071794","article-title":"Implant Fibrosis and the Underappreciated Role of Myofibroblasts in the Foreign Body Reaction","volume":"10","author":"Noskovicova","year":"2021","journal-title":"Cells"},{"key":"2026090701074437400_cit13","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/s41577-022-00761-w","article-title":"Tuning Immunity through Tissue Mechanotransduction","volume":"23","author":"Du","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"2026090701074437400_cit14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252111675","article-title":"SMI-Capsular Fibrosis and Biofilm Dynamics: Molecular Mechanisms, Clinical Implications, and Antimicrobial Approaches","volume":"25","author":"Schoberleitner","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"2026090701074437400_cit15","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.bioactmat.2022.06.003","article-title":"Materials and Extracellular Matrix Rigidity Highlighted in Tissue Damages and Diseases: Implication for Biomaterials Design and Therapeutic Targets","volume":"20","author":"Park","year":"2023","journal-title":"Bioact. Mater."},{"key":"2026090701074437400_cit16","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/s41392-022-01191-9","article-title":"The Hippo Signaling Pathway and Its Implications in Human Health and Disease","volume":"7","author":"Fu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"2026090701074437400_cit17","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2025.149271","article-title":"Single-Cell Transcriptome Analysis Revealing Mechanotransduction via the Hippo\/YAP Pathway in Promoting Fibroblast-to-Myofibroblast Transition and Idiopathic Pulmonary Fibrosis Development","volume":"943","author":"Lu","year":"2025","journal-title":"Gene"},{"key":"2026090701074437400_cit18","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.146243","article-title":"Myofibroblast YAP\/TAZ Activation Is a Key Step in Organ Fibrogenesis","volume":"7","author":"He","year":"2022","journal-title":"JCI Insight"},{"key":"2026090701074437400_cit19","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1172\/jci93561","article-title":"Mechanosensing and Fibrosis","volume":"128","author":"Tschumperlin","year":"2018","journal-title":"J. Clin. Invest."},{"key":"2026090701074437400_cit20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2023.151288","article-title":"Mechanical Stress Regulates the Mechanotransduction and Metabolism of Cardiac Fibroblasts in Fibrotic Cardiac Diseases","volume":"102","author":"Tian","year":"2023","journal-title":"Eur. J. Cell Biol."},{"key":"2026090701074437400_cit21","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1093\/bjd\/ljae384","article-title":"Novel Therapeutic Strategy for Intractable Keloids: Suppression of Intracellular Mechanotransduction and Actin Polymerization via Rho-Kinase Pathway Inhibition","volume":"192","author":"Min","year":"2025","journal-title":"Br. J. Dermatol."},{"key":"2026090701074437400_cit22","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113674","article-title":"YAP\/TAZ Signaling as a Molecular Link between Fibrosis and Cancer","volume":"19","author":"Noguchi","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2026090701074437400_cit23","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1002\/jbm.a.35958","article-title":"The Pathology of the Foreign Body Reaction against Biomaterials","volume":"105","author":"Klopfleisch","year":"2017","journal-title":"J. Biomed. Mater. Res. A"},{"key":"2026090701074437400_cit24","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.coph.2017.07.013","article-title":"Advances in Polymeric Islet Cell Encapsulation Technologies to Limit the Foreign Body Response and Provide Immunoisolation","volume":"36","author":"Ryan","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"2026090701074437400_cit25","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.bjps.2017.12.002","article-title":"The Aetiopathogenesis of Capsular Contracture: A Systematic Review of the Literature","volume":"71","author":"Bachour","year":"2018","journal-title":"J. Plast. Reconstr. Aesthet. Surg."},{"key":"2026090701074437400_cit26","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1132353","article-title":"Extracellular Matrix Stiffness\u2014The Central Cue for Skin Fibrosis","volume":"10","author":"Wang","year":"2023","journal-title":"Front. Mol. Biosci."},{"key":"2026090701074437400_cit27","doi-asserted-by":"publisher","DOI":"10.3390\/cells10050994","article-title":"Mechanosensitive Regulation of Fibrosis","volume":"10","author":"Yang","year":"2021","journal-title":"Cells"},{"key":"2026090701074437400_cit28","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41580-019-0134-2","article-title":"Integrins as Biomechanical Sensors of the Microenvironment","volume":"20","author":"Kechagia","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026090701074437400_cit29","doi-asserted-by":"publisher","first-page":"4349","DOI":"10.1016\/j.bpj.2021.09.010","article-title":"Integrin-Based Mechanosensing through Conformational Deformation","volume":"120","author":"Driscoll","year":"2021","journal-title":"Biophys. J."},{"key":"2026090701074437400_cit30","doi-asserted-by":"publisher","first-page":"3619","DOI":"10.1167\/iovs.17-23580","article-title":"The Role of the RhoA\/ROCK Signaling Pathway in Mechanical Strain-Induced Scleral Myofibroblast Differentiation","volume":"59","author":"Yuan","year":"2018","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"2026090701074437400_cit31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36272-9","article-title":"Vinculin and the Mechanical Response of Adherent Fibroblasts to Matrix Deformation","volume":"8","author":"Rosowski","year":"2018","journal-title":"Sci. Rep."},{"key":"2026090701074437400_cit32","doi-asserted-by":"publisher","first-page":"1680","DOI":"10.1016\/j.bpj.2018.02.019","article-title":"Vinculin Force-Sensitive Dynamics at Focal Adhesions Enable Effective Directed Cell Migration","volume":"114","author":"Rothenberg","year":"2018","journal-title":"Biophys. J."},{"key":"2026090701074437400_cit33","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.673599","article-title":"Mechanoregulation of YAP and TAZ in Cellular Homeostasis and Disease Progression","volume":"9","author":"Cai","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"2026090701074437400_cit34","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/nrm.2017.87","article-title":"Mechanobiology of YAP and TAZ in Physiology and Disease","volume":"18","author":"Panciera","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026090701074437400_cit35","doi-asserted-by":"publisher","first-page":"17693","DOI":"10.1074\/jbc.REV119.007963","article-title":"Control of Cellular Responses to Mechanical Cues through YAP\/TAZ Regulation","volume":"294","author":"Dasgupta","year":"2019","journal-title":"J. Biol. Chem."},{"key":"2026090701074437400_cit36","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay8798","article-title":"Targeting Acid Ceramidase Inhibits YAP\/TAZ Signaling to Reduce Fibrosis in Mice","volume":"12","author":"Alsamman","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"2026090701074437400_cit37","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.jdermsci.2021.09.002","article-title":"Keloid Fibroblasts Have Elevated and Dysfunctional Mechanotransduction Signaling That Is Independent of TGF-\u03b2","volume":"104","author":"Deng","year":"2021","journal-title":"J. Dermatol. Sci."},{"key":"2026090701074437400_cit38","doi-asserted-by":"publisher","first-page":"562","DOI":"10.3390\/antiox10040562","article-title":"The Enzymatic and Non-Enzymatic Function of Myeloperoxidase (MPO) in Inflammatory Communication","volume":"10","author":"Kargapolova","year":"2021","journal-title":"Antioxidants"},{"key":"2026090701074437400_cit39","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.actbio.2022.08.063","article-title":"Mechanosensor YAP Cooperates with TGF-\u03b21 Signaling to Promote Myofibroblast Activation and Matrix Stiffening in a 3D Model of Human Cardiac Fibrosis","volume":"152","author":"Ragazzini","year":"2022","journal-title":"Acta Biomater."},{"key":"2026090701074437400_cit40","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1002\/path.5680","article-title":"TGF-\u03b2 as a Driver of Fibrosis: Physiological Roles and Therapeutic Opportunities","volume":"254","author":"Budi","year":"2021","journal-title":"J. Pathol."},{"key":"2026090701074437400_cit41","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2023.149360","article-title":"Integrin \u03b1V Mediated Activation of Myofibroblast via Mechanoparacrine of Transforming Growth Factor \u03b21 in Promoting Fibrous Scar Formation after Myocardial Infarction","volume":"692","author":"Chen","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026090701074437400_cit42","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.semcdb.2019.12.010","article-title":"TGF-\u03b21\u2014A Truly Transforming Growth Factor in Fibrosis and Immunity","volume":"101","author":"Lodyga","year":"2020","journal-title":"Semin. Cell Dev. Biol."},{"key":"2026090701074437400_cit43","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s40824-018-0147-5","article-title":"Silicone Breast Implant Modification Review: Overcoming Capsular Contracture","volume":"22","author":"Shin","year":"2018","journal-title":"Biomater. Res."},{"key":"2026090701074437400_cit44","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s40824-022-00314-1","article-title":"Advances in Surface Modifications of the Silicone Breast Implant and Impact on Its Biocompatibility and Biointegration","volume":"26","author":"Foroushani","year":"2022","journal-title":"Biomater. Res."},{"key":"2026090701074437400_cit45","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s11926-018-0710-z","article-title":"Matrix Stiffness: The Conductor of Organ Fibrosis","volume":"20","author":"Santos","year":"2018","journal-title":"Curr. Rheumatol. Rep."},{"key":"2026090701074437400_cit46","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1111\/wrr.12889","article-title":"The Hard Problem: Mechanotransduction Perpetuates the Myofibroblast Phenotype in Scleroderma Fibrosis","volume":"29","author":"Leask","year":"2021","journal-title":"Wound Repair Regen."},{"key":"2026090701074437400_cit47","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2020.105802","article-title":"The Extracellular Matrix and Mechanotransduction in Pulmonary Fibrosis","volume":"126","author":"Deng","year":"2020","journal-title":"Int. J. Biochem. Cell Biol."}],"container-title":["ACS Applied Bio Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsabm.6c01259","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article-pdf\/9\/17\/8314\/66540893\/mt-2026-012592.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article-pdf\/9\/17\/8314\/66540893\/mt-2026-012592.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:10:00Z","timestamp":1788768600000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aabmcb\/article\/9\/17\/8314\/5255140\/Stiffness-Dependent-Mechanotransductive-Signaling"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":47,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,8,14]]},"published-print":{"date-parts":[[2026,9,7]]}},"URL":"https:\/\/doi.org\/10.1021\/acsabm.6c01259","relation":{},"ISSN":["2576-6422"],"issn-type":[{"value":"2576-6422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}