Formulation Design of a Recombinant Protein-Based Lung Sealant

Of the 2 million people worldwide diagnosed with lung cancer annually, many will need to receive surgery to remove the tumor. Sutures and staples are used to close lung tissue upon completion of the surgery, but these techniques frequently result in air leakage. Surgical sealants typically supplement sutures and staples to form a better seal, but there are currently no sealants available that meet all the performance criteria for the lung. This work aims to demonstrate the potential of a material containing an elastin-like polypeptide (ELP) modified with adhesive 3,4-dihydroxyphenylalanine (DOPA) residues to function as a sealant in lung applications.

The DOPA-modified protein, mELP, was mixed with iron, periodate, or (hydroxymethyl) phosphonium chloride (THPC) crosslinking molecules to form a hydrogel network. The mELP-based material formulations combined with iron or periodate obtained ambient burst pressures an order of magnitude higher than the transpulmonary pressure typically exerted on lung tissues. When combined with THPC or periodate, mELP formulations had Young’s moduli of 3.9 kPa and 8.8 kPa respectively. The Young’s modulus of the formulation with THPC is within the elastic range of human lung tissue. Formulations with THPC also exhibited minimal volumetric shrinkage over time and equilibrated within 1 hour of application. Formulations with periodate swelled within the first 3 hours to over 3 times its application which could impact adhesion and elasticity. The material shrunk within 6 hours and equilibrated to a final volume less than the initial application volume within 72 hours of application. The results demonstrate the potential of mELP-based formulations to function as a lung sealant.