Acute Respiratory Distress Syndrome (ARDS) is diagnosed in 150,000 patients per year in the United States. These types of lung injury may be caused by severe infection, inhaling dangerous substances, or trauma. ARDS has a high impact on mortality with approximately half of all people diagnosed dying as a result of the injury. No effective treatments exist for ARDS, and ventilator support is necessary for the patient to recover. One reason there are no effective treatments is that pulmonary drug delivery is an area with many challenges that is in need of novel approaches. The lungs have an aggressive innate and adaptive immune response in combination with their complex structure, which makes delivering therapeutics difficult. In order to overcome challenges in pulmonary drug delivery, nanoparticles may be utilized as delivery vehicles. Current nanoparticle approaches such as lipid or polymer-based strategies may be rendered ineffective in the lung through hydrolysis or may have dangerous degradation products. By using naturally-derived extracellular matrix (ECM) proteins for the delivery vehicle, we can achieve an increase therapeutic effect. ECM-based nanoparticles increase therapeutic effect through better cell attachment and regulating the immune response. Additionally, ECM degradation has been shown to be antibacterial, and scaffolds made from these materials have been accepted clinically for repair and reconstruction of other tissues. We hypothesize that engineered ECM nanoparticles will be antibacterial and pro-regenerative to damaged lung tissue, enhancing the effects of delivered therapeutics to treat ARDS. This hypothesis will be tested through two specific aims. In Aim 1 we will quantify the antibiotic and pro-regenerative benefits of ECM nanoparticles delivered in vitro to primary lung epithelium, neutrophils, and macrophages. In Aim 2 we will assess the delivery and regenerative potential of ECM nanoparticles in an in vivo mouse model of lung injury. The ECM nanoparticles formed through electrospray will provide a novel platform for drug delivery of biologics to the distal lung for improved treatment options for ARDS and other lung diseases in the future.