New polyoxazoline loaded patches for hemostasis in experimental liver resection

Edwin A Roozen, Michiel C Warlé, Roger M L M Lomme, Rosa P Félix Lanao, Harry van Goor, Edwin A Roozen, Michiel C Warlé, Roger M L M Lomme, Rosa P Félix Lanao, Harry van Goor

Abstract

A new cost-effective NHS functionalized polyoxazoline (POx) loaded polymer with strong hemostatic properties has been developed. In this study, we investigate POx loaded hemostatic patches regarding hemostatic efficacy, local inflammatory reaction and wound-healing, as compared to the non-POx treated blanks and commercially available hemostatic products. Hundred and ten rats divided into 11 groups of 10 animals underwent partial liver lobe resection. Eight groups received experimental patches, two groups commercially available hemostatic patches (TachoSil® and Veriset™, positive controls), one group with gauzes (negative control). Each animal received twice a patch with a size 1.5 × 2.5 cm, on each partially resected lobe. Primary endpoint was time to hemostasis (TTH). The rats were sacrificed at different time points (1, 3, or 7 days) to measure local inflammatory response and early wound healing. Of the POx loaded patches, GFC NHS-POx (TTH 20.4 s, p = .019) and GFC-NHS-POx1.5 (TTH 0.0 s, p = .003) showed significantly faster TTH compared to TachoSil® (TTH 95.4 s), and were comparable to Veriset™ (TTH 17.0 s). Three patches, GFC-NHS-POx 1.5 (TTH 0.0 s, p = .016), ORC NHS-POx:NU-POx (TTH 91.4 s, p = .033), and ORC-PLGA NHS-POx:NU-POx (TTH 105.6 s, p = .04) had a lower TTH compared to their own blank carrier (TTH 74.9, 157.8, and 195.7 s, respectively). With regard to biocompatibility, all POx loaded patches showed results comparable to TachoSil® and Veriset™. NHS-POx-loaded hemostatic patch demonstrate fast and effective hemostasis, comparable or better than commercially available hemostatic patches, with similar early biocompatibility.

Keywords: biocompatibility; hemostatic patch; histology; liver surgery; polyoxazoline derivate.

Conflict of interest statement

There are no conflicts of interest to declare. R.P. Félix Lanao and E.A. Roozen are currently fulltime employed at GATT Technologies BV.

© 2021 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals LLC.

Figures

FIGURE 1
FIGURE 1
(A) Liver lobe on paper, (B) partial liver resection, (C) liver placed on patch (and fold around), (D) digital pressure for 1 min, (E) Check TTH, and (F) closing with suture
FIGURE 2
FIGURE 2
Time to hemostasis in seconds (bars represent average with standard error). ⊗ significantly different with TachoSil® (─ ─ ). ∇ significantly different with their own blank
FIGURE A1
FIGURE A1
(A) Normal liver, (B) patch, (C) wound area, (D) necrosis, (E) blood cloth, and (F) inflammatory cells
FIGURE A2
FIGURE A2
(A) Normal liver, (B) patch, (C) wound area, and (D) new (granulation) tissue

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