Ultrasound‐Triggered Enzymatic Gelation

• Published in: Advanced materials (Weinheim) 2020-02, Vol.32 (7), p.e1905914-n/a
• Main Authors: Nele, Valeria, Schutt, Carolyn E., Wojciechowski, Jonathan P., Kit‐Anan, Worrapong, Doutch, James J., Armstrong, James P. K., Stevens, Molly M.
• Format: Article
• Language: English
• Subjects: Calcium Chloride - chemistry; Calcium ions; Catalysis; Cross-Linking Reagents - chemistry; Crosslinking; Enzyme kinetics; enzymes; Enzymes - chemistry; Fibrinogen; Fibrinogen - chemistry; Gelation; Hydrogels; Hydrogels - chemistry; Kinetics; Light irradiation; liposomes; Liposomes - chemistry; Microbubbles; Organic chemistry; Phosphatidylethanolamines - chemistry; Phosphorylcholine - chemistry; Polyethylene Glycols - chemistry; Reaction kinetics; Ultrasonic imaging; Ultrasonic Waves; Ultrasound
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.201905914

Hydrogels are formed using various triggers, including light irradiation, pH adjustment, heating, cooling, or chemical addition. Here, a new method for forming hydrogels is introduced: ultrasound‐triggered enzymatic gelation. Specifically, ultrasound is used as a stimulus to liberate liposomal calcium ions, which then trigger the enzymatic activity of transglutaminase. The activated enzyme catalyzes the formation of fibrinogen hydrogels through covalent intermolecular crosslinking. The catalysis and gelation processes are monitored in real time and both the enzyme kinetics and final hydrogel properties are controlled by varying the initial ultrasound exposure time. This technology is extended to microbubble–liposome conjugates, which exhibit a stronger response to the applied acoustic field and are also used for ultrasound‐triggered enzymatic hydrogelation. To the best of the knowledge, these results are the first instance in which ultrasound is used as a trigger for either enzyme catalysis or enzymatic hydrogelation. This approach is highly versatile and can be readily applied to different ion‐dependent enzymes or gelation systems. Moreover, this work paves the way for the use of ultrasound as a remote trigger for in vivo hydrogelation. Ultrasound is used to trigger the release of calcium ions from liposomes to activate a calcium‐dependent transglutaminase. The activated transglutaminase is then able to catalyze the formation of fibrinogen hydrogels. Ultrasound is shown to modulate the enzyme catalysis, the kinetics of hydrogelation, and the hydrogel properties. The capabilities of this technology are also extended to microbubble–liposome conjugates.