Sealing effectiveness of a novel NHS-POx based patch: experiments in a dynamic ex vivo porcine lung

Abstract

Background: Sealants are used to prevent prolonged pulmonary air leakage (PAL) after lung resections (incidence 5.6-30%). However, clinical evidence to support sealant use is insufficient, with an unmet need for a more effective product. We compared a novel gelatin patch impregnated with functionalized polyoxazolines (NHS-POx) (GATT-Patch) to commercially available sealant products.

Methods: GATT-Patch Single/Double layers were compared to Progel^®, Coseal^®, Hemopatch^® and TachoSil^® in an ex vivo porcine lung model (first experiment). Based on these results, a second head-to-head comparison between GATT-Patch Single and Hemopatch^® was performed. Air leakage (AL) was assessed in three settings using increasing ventilatory pressures (max =70 cmH₂O): (I) baseline, (II) with 25 mm × 25 mm superficial pleural defect, and (III) after sealant application. Lungs floating on saline (37 ℃) were video recorded for visual AL assessment. Pressure and tidal volumes were collected from the ventilator, and bursting pressure (BP), AL and AL-reduction were determined.

Results: Per sealant 10 measurements were performed (both experiments). In the first experiment, BP was superior for GATT-Patch Double (60±24 cmH₂O) compared to TachoSil^® (30±11 cmH₂O, P<0.001), Hemopatch^® (33±6 cmH₂O, P=0.006), Coseal^® (25±13 cmH₂O, P=0.001) and Progel^® (33±11 cmH₂O, P=0.005). AL-reduction was superior for GATT-Patch Double (100%±1%) compared to Hemopatch^® (46%±50%, P=0.010) and TachoSil^® (31%±29%, P<0.001), and also for GATT-Patch Single (100%±14%, P=0.004) and Progel (89%±40%, P=0.027) compared to TachoSil^®. In the second experiment, GATT-Patch Single was superior regarding BP (45±10 vs. 40±6 cmH₂O, P=0.043) and AL-reduction (100%±11% vs. 68%±40%, P=0.043) when compared to Hemopatch^®.

Conclusions: The novel NHS-POx patch shows promise as a lung sealant, demonstrating elevated BP, good adhesive strength and a superior AL-reduction.

Keywords: Air leak; biomaterials; ex vivo; experimental; lung sealant; lung surgery.

Figure 1

Overview of ex vivo porcine lung model. (A) Standardized pleural defect (25 mm ×25 mm), made at static lung inflation pressure of 10 cmH₂O. (B) Experimental setup. (C) Schematic of experimental setup. DAQ, data-acquisition setup; Servo-i, mechanical ventilator; HD, high definition; NaCl, physiological saline solution; C, camera; HC, heater-cooler; HE, heat-exchanger; CP, centrifugal pump.

Video 1

Failure mechanisms of all sealant groups in the first experiment.

Figure 2

First experiment main results. (A) Bursting pressure; (B) air leak reduction. Presented as median, interquartile range and range. Statistical analysis is performed using a Kruskal-Wallis test (two-tailed) and P values are adjusted using the Bonferroni correction in post-hoc analysis. *, statistically significant at P<0.05. GATT-P, gelatin patch impregnated with N-hydroxysuccimide ester functionalized poly (2-oxazolines).

Figure 3

Modes of failure (adhesive or cohesive failure) (A) TachoSil^® (adhesive), at 30 cmH₂O ventilatory pressure. (B) Coseal^® (cohesive), at 50 cmH₂O. (C) Progel^® (cohesive), at 40 cmH₂O. (D) Hemopatch^® (adhesive), at 40 cmH₂O. (E) GATT-Patch Single (cohesive), at 70 cmH₂O. (F) GATT-Patch Double (cohesive), at 55 cmH₂O. Note: all lesions (25 mm × 25 mm) were made at 10 cmH₂O, patches were applied at 5 cmH₂O and gels on a deflated lung.

Figure 4

Second experiment main results. (A) Bursting pressure; (B) air leak reduction. Presented as median, interquartile range and range. Statistical analysis is performed using a Mann-Whitney U test (two-tailed). *, statistically significant at P<0.05. GATT-P, gelatin patch impregnated with N-hydroxysuccimide ester functionalized poly (2-oxazolines).