{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:08:55Z","timestamp":1784030935872,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,10]]},"group-title":"Bioengineering","reference-count":45,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL164650"],"award-info":[{"award-number":["R01HL164650"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1F31CA298728"],"award-info":[{"award-number":["1F31CA298728"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Heparin, a naturally derived glycosaminoglycan, is the most commonly used anti-thromboembolic in the world. However, the biological origin of heparin inherently results in batch-to-batch variability, large dispersity indexes, and potential contamination, leading to inconsistent activity and patient-dependent dose-response. As such, new synthetic anticoagulants are of keen interest, particularly those that mimic heparin while being amenable to alterations in polymer structure and composition for performance optimization. Herein, we report the strategy, synthesis, and evaluation of well-defined, regioselectively functionalized di-sulfated polyamidosaccharides (\n                  <jats:bold>disulPASs<\/jats:bold>\n                  ) including exploration of the structure-function relationship of molecular weight and sulfation density on anticoagulant activity. Polymerization of an orthogonally protected \u00fd-lactam monomer via anionic ring-opening, followed by selective deprotection and sulfation reactions affords disulPAS. Similar to heparin,\n                  <jats:bold>disulPAS<\/jats:bold>\n                  s elongate clotting time through the intrinsic and extrinsic pathways, showing molecular weight and dose-dependent responses in clotting time; are non-cytotoxic and non-hemolytic, partially neutralized by protamine sulfate, and unlike heparin, are not degraded by heparinases. As compared to less sulfated and randomly sulfated iterations of PAS,\n                  <jats:bold>disulPAS<\/jats:bold>\n                  performs superiorly, with\n                  <jats:italic>in vitro<\/jats:italic>\n                  and\n                  <jats:italic>in vivo<\/jats:italic>\n                  clotting activity most similar to native heparin.\n                <\/jats:p>","DOI":"10.64898\/2026.07.09.737190","type":"posted-content","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T10:00:27Z","timestamp":1783677627000},"source":"Crossref","is-referenced-by-count":0,"title":["Regio-selective sulfation of heparin mimicking polymers defines in vivo activity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5003-2081","authenticated-orcid":false,"given":"Madeline K.","family":"Loffredo","sequence":"first","affiliation":[{"name":"Division of Materials Science and Engineering, Boston University, Boston, MA, 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7124-8188","authenticated-orcid":false,"given":"Hyun Ok","family":"Ham","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9739-8454","authenticated-orcid":false,"given":"Maria","family":"Varghese","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Boston University, Boston, MA, 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1963-3695","authenticated-orcid":false,"given":"Carolyn A","family":"Haller","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6184-4571","authenticated-orcid":false,"given":"Elliot L.","family":"Chaikof","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5453-3668","authenticated-orcid":false,"given":"Mark W.","family":"Grinstaff","sequence":"additional","affiliation":[{"name":"Division of Materials Science and Engineering, Boston University, Boston, MA, 02215, USA"},{"name":"Department of Chemistry, Boston University, Boston, MA, 02215, USA"},{"name":"Department of Biomedical Engineering, Boston University, Boston, MA, 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071404452711000_2026.07.09.737190v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carres.2014.06.023"},{"key":"2026071404452711000_2026.07.09.737190v1.2","doi-asserted-by":"publisher","DOI":"10.1186\/s12959-021-00318-2"},{"key":"2026071404452711000_2026.07.09.737190v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2019.03.104"},{"key":"2026071404452711000_2026.07.09.737190v1.4","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1614170"},{"key":"2026071404452711000_2026.07.09.737190v1.5","doi-asserted-by":"crossref","unstructured":"Casu B . Structure and Active Domains of Heparin. Chemistry and Biology of Heparin and Heparin Sulfate. Elsevier Science; 2005.","DOI":"10.1016\/B978-008044859-6\/50002-2"},{"key":"2026071404452711000_2026.07.09.737190v1.6","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-996063"},{"key":"2026071404452711000_2026.07.09.737190v1.7","doi-asserted-by":"publisher","DOI":"10.1097\/00001721-199402000-00012"},{"key":"2026071404452711000_2026.07.09.737190v1.8","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.53.4.691"},{"key":"2026071404452711000_2026.07.09.737190v1.9","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.86.5.1370"},{"key":"2026071404452711000_2026.07.09.737190v1.10","doi-asserted-by":"publisher","DOI":"10.1039\/b819896a"},{"key":"2026071404452711000_2026.07.09.737190v1.11","doi-asserted-by":"publisher","DOI":"10.1177\/0267659112462274"},{"key":"2026071404452711000_2026.07.09.737190v1.12","doi-asserted-by":"publisher","DOI":"10.1177\/1076029619878786"},{"key":"2026071404452711000_2026.07.09.737190v1.13","unstructured":"Gale J . 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