Electrosprayed extracellular matrix nanoparticles induce a pro-regenerative cell response.

Decellularized extracellular matrix (ECM) is an effective tissue repair scaffold. Additionally, ECM has recently been shown to be protective to the lungs. However, current processing is inadequate for effective delivery of ECM to the lungs. Processing methods, such as milling, produce large variability in particle sizes. The size variation produced is ineffective at treating the lung because only a small range of sizes reach the distal regions of the alveoli. The aim of this work is to formulate decellularized ECM to reach the distal lung while retaining the pro-regenerative effects of ECM. We first digested the protein in acid and then electrosprayed the solution into nanoparticles. The average size of the nanoparticles was 225 (±67) nm, within size requirements to reach the alveoli. After characterizing the particles, we measured cytotoxicity of the nanoparticles. Adding 0.125 mg/ml of nanoparticles to the media increased cellular proliferation in A549 alveolar epithelial cells and caused no cytotoxicity in BEAS-2B cells. We added the formed nanoparticles to macrophages derived from murine bone marrow-derived monocytes. The macrophages exposed to the formed nanoparticles expressed cell surface marker CD206 (mannose receptor C type 1), commonly attributed to a pro-regeneration phenotype. Electrosprayed ECM formed nanoparticles may improve bronchoalveolar deposition while maintaining the pro-regenerative benefits shown by other decellularized ECM materials.