Novel innovative ultra-elastic and instantly adhesive hydrogel patches to prevent air leak after lung surgery - ABSTRACT Air leak after lung surgery, especially prolonged air leak (PAL) (≥ 6 days) is the bane of existence for thoracic surgeons and patients. Air leaks arise from 3 sources after lung surgery: through a staple line placed across lung tissue, as part of lung resection, air leaking from a lung surface opened to separate incomplete fissures to remove a lobe; and Injury to lung tissue unrelated to a lung resection. Air leak after lung surgery requires a chest tube, often prolongs hospitalization, increases cost and death rate, and decreases quality of life (QOL). There are strategies to decrease air leak after lung surgeries, an FDA-approved sealant, and strategies to discharge patients home with a chest tube. We propose a way to eliminate air leaks after lung resection. This would be the most cost-effective way to facilitate early ambulation, reduce pain, prevent chest tubes, and improve QOL after lung resection. We developed anisotropic and auxetic hydrogel patches (PAAx) that can be placed adherent to the lung surface and stretch with lung movement. Therapeutics can be applied to lung surfaces on both sides of these patches. We showed in rats that air leaks from ventilated perforated lung tissue can be sealed by application of fibrinogen to the side of the PAAx applied to the lung, then thrombin applied on the opposite side of the patch. This combination allows fibrin to seal the holes in the lung and helps hold the patch in place. This results in prevention of air leak under positive pressure ventilation, even if tidal volume (TV) is increased to 15 ml/kg. We showed similar results in porcine lungs in an ex-vivo model. Air leak after perforation with an 18-gauge needle was stopped by application of a PAAx treated with fibrinogen and thrombin (F&T), even with inflation to TV of 15 ml/kg. We will test the hypothesis that these PAAx when applied to the surface of lungs in rats with perforations and lung resections, and in pigs after multiple wedge resections and non-anatomic lung resections will have air leaks stopped so that a chest tube will not be required after lung surgery. This hypothesis will be tested by accomplishing these specific aims: Aim 1: To optimize patch degradation rate and elastic properties using in vitro studies. Aim 2: To determine if application of fibrinogen and thrombin (F&T) to PAAx patches will prevent pneumothorax (PTX) compared to F&T alone using survival rat lung injury models. PTX will be quantified by CT scan 3 and 10 days after lung injury, then injured lung areas will undergo histologic examination to assess inflammation from the patch. Aim 3: To determine if PAAx/F&T patches can prevent air leak in non-survival large animal (porcine) lung models from staple lines after wedge resection, by treating staple lines, and open lung surfaces in live anesthetized pigs. Many patients have air leaks after lung resection. Some are discharged home with chest drainage systems. If any air leak following lung surgery could be consistently eliminated, chest tubes would be unnecessary, complications and cost could be substantially reduced, and QOL improved for patients having lung surgery. These novel hydrogel patches with FDA-approved therapeutics (F&T) may provide an innovative solution to a vexing clinical problem.
