{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T08:44:09Z","timestamp":1775983449090,"version":"3.50.1"},"posted":{"date-parts":[[2025,6,3]]},"group-title":"Biophysics","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NSF Science and Technology Center for Engineering Biology","award":["CMMI 1548571"],"award-info":[{"award-number":["CMMI 1548571"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AR077793"],"award-info":[{"award-number":["R01AR077793"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000854","name":"International Human Frontier Science Program Organization","doi-asserted-by":"crossref","award":["HFSP-RGP016\/2024"],"award-info":[{"award-number":["HFSP-RGP016\/2024"]}],"id":[{"id":"10.13039\/501100000854","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Fibrotic encapsulation around medical implants affects millions of patients annually. Current approaches targeting inflammation or implant material properties have failed clinically, but the mechanical origins of implant-induced fibrosis remain unexplored. Here, we demonstrate that directional imbalance of mechanical forces (\u201ctension anisotropy\u201d) is the primary driver of fibroblast activation at implant-tissue interfaces, and that it can be eliminated through adhesive bonding strategies. Computational modeling reveals a mechanistic basis for successful adhesive anti-fibrotic interfaces: conventional sutured implants generate highly anisotropic stress fields between discrete suture anchor points that activate fibroblasts, while adhesive interfaces distribute forces isotropically, maintaining a mechanical environment that does not activate fibroblasts.\n                  <jats:italic>In vivo<\/jats:italic>\n                  experiments from the literature across multiple animal models confirm these predictions: as predicted, adhesive interfaces completely prevent fibrotic capsule formation for up to 12 weeks across diverse organs, while maintaining identical implant composition and geometry compared to sutured controls. Results establish tension anisotropy as a mechanical regulator of implant fibrosis and provide a mechanistic foundation explaining why adhesive interfaces succeed where all previous anti-fibrotic strategies have failed. By addressing the root mechanical cause of fibrosis, this mechanobiology-driven approach may enable a universal approach for preventing fibrosis across all categories of implantable medical devices.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance statement<\/jats:title>\n                  <jats:p>Millions of patients suffer from medical device failure due to fibrotic encapsulation, in which a surgically implanted item such as pacemaker leads or a vascular graft loses function by becoming covered with scar tissue. Implants affixed to soft tissues by sutures are especially prone to this form of failure, but implants affixed with a recently invented adhesive are not. We present the discovery that directional imbalance of forces (\u201ctension anisotropy\u201d) drives conversion of healing tissue into scar tissue. Conventional sutured implants create highly anisotropic stress fields between anchor points that activate fibroblasts, while adhesive interfaces distribute forces isotropically, attenuating scarring. This mechanistic insight explains why adhesive implant-tissue interfaces successfully prevent fibrotic capsule formation across multiple animal models and organ systems, where all previous anti-fibrotic approaches have failed. By addressing root mechanical causes of fibrotic remodeling, this discovery provides a pathway for clinical remediation of fibrotic encapsulation.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.06.01.657311","type":"posted-content","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T05:30:42Z","timestamp":1749015042000},"source":"Crossref","is-referenced-by-count":0,"title":["Adhesive implant interfaces prevent fibrosis by disrupting mechanobiological feedback"],"prefix":"10.64898","author":[{"given":"Mohammad","family":"Jafari","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering, New Jersey Institute of Technology, Newark, NJ"},{"name":"NSF Science and Technology Center for Engineering Mechanobiology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bastien FG","family":"Aymon","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Hong","sequence":"additional","affiliation":[{"name":"NSF Science and Technology Center for Engineering Mechanobiology"},{"name":"Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delaram","family":"Shakiba","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy M","family":"Genin","sequence":"additional","affiliation":[{"name":"NSF Science and Technology Center for Engineering Mechanobiology"},{"name":"Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis"},{"name":"Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuanhe","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA"},{"name":"Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farid","family":"Alisafaei","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, New Jersey Institute of Technology, Newark, NJ"},{"name":"NSF Science and Technology Center for Engineering 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