{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T06:46:00Z","timestamp":1775976360291,"version":"3.50.1"},"posted":{"date-parts":[[2025,5,23]]},"group-title":"Bioengineering","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"crossref","award":["INV-033156"],"award-info":[{"award-number":["INV-033156"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"crossref","award":["INV-064313"],"award-info":[{"award-number":["INV-064313"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DP2DA056107"],"award-info":[{"award-number":["DP2DA056107"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Reversible contraceptives empower women to prevent unintended pregnancies and enable family planning. However, the need for frequent dosing with pills or injections often leads to suboptimal medication adherence and reduced effectiveness\u2013an issue common to many chronic conditions. Long-acting drug delivery implants offer a compelling alternative by enabling autonomous, multi-year drug release, thereby improving real-world adherence and treatment outcomes. However, user acceptability and access are limited by need for invasive insertion and surgical end-of-life removal, particularly in low-resource settings, as well as by limited drug loading and suboptimal drug utilization efficiency, which constrain both the duration of therapy and the range of drugs that can be effectively delivered.<\/jats:p>\n                <jats:p>\n                  To address these limitations, we developed the Monolithic Shape-shifting Absorbable Implants for Chronic Care (MoSAIC) platform\u2013a minimally invasive, fully bioresorbable system that integrates compacted drug formulations with a space-efficient device architecture. This approach reduces implant size, eliminates the need for surgical removal, and prolongs therapeutic duration compared to existing implants. We develop compacted formulations of the contraceptive drug levonorgestrel (LNG), and other poorly water-solubility drugs, demonstrating exceptional drug loading (100% w\/w) and multi-year sustained drug release\n                  <jats:italic>via<\/jats:italic>\n                  surface-mediated dissolution in rats. When incorporated into MoSAIC devices, these formulations enable high-efficiency drug loading and zero-order drug release kinetics with geometrically tunable rates and durations. As a result, MoSAIC systems can be designed to be smaller, less invasive, and\/or longer lasting than current contraceptive implants such as Jadelle\u00ae and Nexplanon\u00ae.\n                <\/jats:p>\n                <jats:p>The MoSAIC platform expands access to reversible contraception and supports long-term medication adherence, with the potential to improve health outcomes and quality of life. More broadly, it provides a flexible approach for delivering other potent, low-solubility therapeutics and lays the foundation for a \u201cdose it and forget it\u201d paradigm in chronic disease management, where adherence is designed into the therapy itself.<\/jats:p>","DOI":"10.1101\/2025.05.18.654764","type":"posted-content","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T18:05:10Z","timestamp":1748023510000},"source":"Crossref","is-referenced-by-count":0,"title":["Monolithic Shape-Shifting Absorbable Implants for Long-Term Contraception"],"prefix":"10.64898","author":[{"given":"Jason","family":"Li","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"},{"name":"David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; Cambridge, MA 02139, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 20142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin G.","family":"Clark","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology; Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parmiss","family":"Khosravi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology; Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Cotter","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 20142, USA"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology; Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia Y.","family":"Liang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology; Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan R.","family":"Ling","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuyan","family":"Su","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kent J.","family":"Qi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia","family":"Codreanu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan","family":"D\u2019Orio","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 20142, USA"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology; Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivy Tianqin","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 20142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia E.","family":"Green","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 20142, USA"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology; Cambridge, MA 02139, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Murawska","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 20142, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Lopes","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Harvard Medical School; Boston, MA 02115, USA"},{"name":"David H. 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