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Currently available commercial hemostatic materials for non\u2010compressible hemorrhage are plagued by issues such as poor sealing ability and insufficient hemostatic performance. In the current work, tetra\u2010PEG\u2010succinimidyl glutarate (TPEG\u2010SG), carboxymethyl chitosan (CMCS), and the coagulation factor Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    were used as the primary ingredients to create a covalent\u2010ionic hybrid crosslinked hemostatic agent TPEG\u2010SG\/CMCS\/Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    . The optimal formula of hemostatic agent was screened by using response surface methodology. The obtained hemostatic agent TPEG\u2010SG\/CMCS\/Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    could achieve rapid and ultra\u2010high sealing ability, with a burst pressure of 354\u00a0mmHg. It also demonstrated excellent hemostatic ability in vivo, outperforming the commercial fibrin glue in hemostasis including mouse liver and inferior vena cava hemorrhage models, rabbit renal incision, partial hepatectomy, femoral artery puncture, and lethal rabbit carotid artery puncture hemorrhage models, showing great potential in non\u2010compressible hemorrhage hemostasis. In addition, in the mouse full\u2010thickness skin incision model, the hemostatic agent was superior to fibrin glue in wound closure and repair. Overall, the TPEG\u2010SG\/CMCS\/Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    hemostatic agent showed promising clinical application potential in the management of non\u2010compressible hemorrhage.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202503697","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T07:54:27Z","timestamp":1768895667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bio\u2010Inspired In Situ Injectable Hemostatic Agent with Covalent\u2010Ionic Hybrid Network for Non\u2010Compressible Hemorrhage"],"prefix":"10.1002","volume":"15","author":[{"given":"Xiao\u2010Suan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zedong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Yao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Fourth Military Medical University  Xi'an China"},{"name":"Department of Pharmacy Xijing 986 Hospital Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pharmacology of the State Administration of Traditional Chinese Medicine Fourth Military Medical University  Xi'an China"},{"name":"Department of Chemistry School of Pharmacy Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tang\u2010Rui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Yuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Fourth Military Medical University  Xi'an China"},{"name":"Key Laboratory of Pharmacology of the State Administration of Traditional Chinese Medicine Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang\u2010Le","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Fourth Military Medical University  Xi'an China"},{"name":"Key Laboratory of Pharmacology of the State Administration of Traditional Chinese Medicine Fourth Military Medical University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"issue":"6","key":"e_1_2_9_2_1","first-page":"S3","article-title":"Impact of Hemorrhage on Trauma Outcome: an Overview of Epidemiology, Clinical Presentations, and Therapeutic Considerations","volume":"60","author":"Kauvar D. 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