In situ forming chitosan-based hydrogel as a lung sealant for biological lung volume reduction

Abstract

Biological lung volume reduction (BLVR) using lung sealant has received more attention recently as a new non-surgical approach to emphysema treatment. Many tissue sealants have been studied but only a few have been proposed for BLVR. In this work, we prepared in situ forming chitosan-based hydrogels (CSG) using covalent cross-linking of chitosan and genipin in the cooperation of ionic interaction between chitosan and sodium orthophosphate hydrate (Na3PO4·12H2O) and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy and rheological methods. CSG showed short gelation time (8min), high swelling ratio (>100%) and non-toxicity (3T3 mouse fibroblast cell viability >80%) under physiological conditions. The application of lung sealant for BLVR was tested in a Chinese dog and evaluated by chest computed tomography. After 3 weeks of the installation of CSG in bronchopulmonary segment, the gel formation was detected at a localized region of bronchi and the local atelectasis occurred. Our findings indicate that this chitosan-based hydrogel is a promising new candidate for use as a lung sealant for BLVR.