Continued Clinical Development of a Novel Pleural and Tracheal Sealant - PROJECT ABSTRACT A range of lung diseases and critical illnesses, including complications of mechanical ventilation, as well as trauma can result in air leak from the lung (pneumothorax). These leaks often require immediate life-saving measures to stabilize for subsequent reparative interventions. Continued care can further be complicated by chronic air leaks (bronchopleural fistula, BPF) requiring need for prolonged chest tube drainage and/or invasive surgery and can be difficult to manage. These all result in significantly increased morbidity, mortality, hospital stays, health care costs, and other complications. However, at present there are only limited options for directly repairing pleural leaks, particularly chronic leaks, and new therapeutic interventions are critically needed. We have developed a novel sealant patch consisting of dopamine-conjugated methacrylated seaweed-derived alginate (ALG-MA-DA). The patch has desired materials properties, including tailorable stiffness, elasticity, and adhesive strength, and is easily transported and applied to the lung surface. We have further designed, tested, and documented safety and efficacy in initial pre-clinical studies utilizing ex vivo and in vivo small and large (rat/pig) models of lung injuries. We now propose to further define optimal GMP-grade manufacturing, sterilization, and storage conditions, and to further define longitudinal safety and efficacy in the small (rat) and large (pig) animal models of pleural injuries. This will include assessing sealant patch efficacy with larger wounds and also assess efficacy of shelf-stored patches. We will also engage with the FDA for development of initial clinical investigations and a Pre-Sub (Q) meeting is scheduled for April 10, 2023. The studies will be done with our industry partner Akina Inc and Accelerator partner CELLINK LLC. The developed system will fall under the FDA category as a class III medical device given both its invasive application and its use in supporting or sustaining human life. As such, the proposed Specific Aims are consonant with the goals of the NIH Catalyze Program HL-23-014, “Product Definition Device Prototype Testing and Design Modification”. 1. To define optimal sterilization, preservation, and storage conditions of ready-to-use research-grade patches and apply this to manufacture and characterization of GMP-grade ALG-MA-DA patches 2. To further define ALG-MA-DA patch safety and efficacy in long-term rat and pig pleural injury models 3. To engage with the FDA and initiate an IND for initial clinical investigation.
