Triggered release of calcium from lipid vesicles: a bioinspired strategy for rapid gelation of polysaccharide and protein hydrogels.

The bioinspired strategy of triggered release of Ca2+ from liposomal compartments was used to induce rapid gelation of polysaccharide and protein-based hydrogels. Thermally triggerable liposomes were designed by entrapping CaCl2 within liposomes constructed of 90% dipalmitoylphosphatidylcholine and 10% dimyristoylphosphatidylcholine. These liposomes released greater than 90% of entrapped Ca2+ when heated to 37 degrees C. A precursor fluid containing liposomes suspended in aqueous sodium alginate remained fluid for several days at room temperature but gelled rapidly when heated to 37 degrees C, as a result of Ca2+ release and formation of crosslinked Ca-alginate. Alternatively, thermally triggered Ca2+ release from liposomes was used to activate enzyme-catalyzed crosslinking of proteins to form hydrogels. A mixture of Ca-loaded liposomes, fibrinogen, and a Ca2+-dependent transglutaminase enzyme (either human recombinant FXIII or guinea pig liver transglutaminase) remained fluid indefinitely when stored at room temperature, but gelled rapidly when heated to 37 degrees C. SDS-PAGE of the reaction mixture revealed that gelation was due to enzymatic crosslinking of the alpha and gamma chains of fibrinogen, and oscillating rheometry revealed gel formation within 10 min of heating to 37 degrees C. This new approach may be useful for developing rapidly gelling injectable biomaterials that can be stored at room temperature and injected in a minimally invasive manner into a body tissue or cavity, upon which rapid solidification would occur. This versatile bioinspired strategy could be utilized for the delivery of biomaterials for tissue repair and reconstruction, and local site-directed drug delivery.