A rapid hemostatic sealant can save a patient's life from shock and death due to severe trauma or excessive bleeding from the wound site during surgery. However, an ideal hemostatic sealant needs to meet the standards of safety, efficacy, usability, cost, and approvability and overcome new challenges. Here, we devised a combinatorial hemostatic sealant of PEG succinimidyl glutarate-based cross-linking branched polymers (CBPs) and the active hemostatic peptide (AHP). After ex vivo optimization, the best hemostatic combination was called an active cross-linking hemostatic sealant (ACHS). Interestingly, ACHS formed cross-links with serum proteins, blood cells, and tissue and interconnected coating on blood cells, which might induce hemostasis and tissue adhesion based on SEM images. Moreover, ACHS showed the highest coagulation efficacy, formation, and agglomeration of thrombi within 12 s, and in vitro biocompatibility. Mouse model experiments represented rapid hemostasis within 1 min, wound closure of the liver incision, and less bleeding than the commercialized sealant with tissue biocompatibility. ACHS has the advantages of rapid hemostasis, mild sealant, and easy supply by chemical synthesis without inhibition by anticoagulants, which might minimize bacterial infection by immediate wound closure. Therefore, ACHS could become a new-type hemostatic sealant to match surgical needs for internal bleeding.
Keywords: active cross-linking hemostatic sealant (ACHS); active hemostatic peptide (AHP); cross-linking branched polymer (CBP); polyethylene glycol-succinimidyl glutarate (PEG-SG).
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