Efficacy of a novel polyoxazoline-based hemostatic patch in liver and spleen surgery

World J Emerg Surg. 2023 Mar 14;18(1):19. doi: 10.1186/s13017-023-00483-x.

Abstract

Background: A new hemostatic sealant based on a N-hydroxy-succinimide polyoxazoline (NHS-POx) polymer was evaluated to determine hemostatic efficacy and long-term wound healing and adverse effects in a large animal model of parenchymal organ surgical bleeds.

Methods: Experiment 1 included 20 pigs that were treated with two NHS-POx patch prototypes [a gelatin fibrous carrier (GFC) with NHS-POx and an oxidized regenerated cellulose (ORC) with poly(lactic-co-glycolic acid)-NHS-POx:NU-POx (nucleophilically activated polyoxazoline)], a blank gelatin patch (GFC Blank), TachoSil® and Veriset™ to stop moderate liver and spleen punch bleedings. After various survival periods (1-6 weeks), pigs were re-operated to evaluate patch degradation and parenchymal healing. During the re-operation, experiment 2 was performed: partial liver and spleen resections with severe bleeding, and hemostatic efficacy was evaluated under normal and heparinized conditions of the two previous prototypes and one additional NHS-POx patch. In the third experiment an improved NHS-POx patch (GATT-Patch; GFC-NHS-POx and added 20% as nucleophilically activated polyoxazoline; NU-POx) was compared with TachoSil®, Veriset™ and GFC Blank on punch bleedings and partial liver and spleen resections for rapid (10s) hemostatic efficacy.

Results: NHS-POx-based patches showed better (GFC-NHS-POx 83.1%, ORC-PLGA-NHS-POx: NU-POx 98.3%) hemostatic efficacy compared to TachoSil® (25.0%) and GFC Blank (43.3%), and comparable efficacy with Veriset™ (96.7%) on moderate standardized punch bleedings on liver and spleen. All patches demonstrated gradual degradation over 6 weeks with a reduced local inflammation rate and an improved wound healing. For severe bleedings under non-heparinized conditions, hemostasis was achieved in 100% for Veriset™, 40% for TachoSil and 80-100% for the three NHS-POx prototypes; similar differences between patches remained for heparinized conditions. In experiment 3, GATT-Patch, Veriset™, TachoSil and GFC Blank reached hemostasis after 10s in 100%, 42.8%, 7.1% and 14.3%, respectively, and at 3 min in 100%, 100%, 14.3% and 35.7%, respectively, on all liver and spleen punctures and resections.

Conclusions: NHS-POx-based patches, and particularly the GATT-Patch, are fast in achieving effective hemostatic sealing on standardized moderate and severe bleedings without apparent long-term adverse events.

Trial registration: ClinicalTrials.gov NCT04819945.

Keywords: GATT-patch; Hemostasis; Liver; Patch; Porcine; Sealant; Sealing; Spleen; Surgical bleeding; TachoSil®; Veriset™.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Loss, Surgical
  • Cellulose, Oxidized* / pharmacology
  • Gelatin / pharmacology
  • Hemostasis
  • Hemostatics* / pharmacology
  • Hemostatics* / therapeutic use
  • Liver / surgery
  • Spleen / surgery
  • Swine

Substances

  • Hemostatics
  • Gelatin
  • Cellulose, Oxidized

Associated data

  • ClinicalTrials.gov/NCT04819945