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

Abstract

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 (10 seconds) 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 10 seconds in 100%, 42.8%, 7.1% and 14.3% respectively, and at 3 minutes 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.