@article{ab0c93b4cbce415495518dbe20307051,
title = "Ultrasound-Triggered Enzymatic Gelation",
abstract = "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.",
keywords = "enzymes, hydrogels, liposomes, microbubbles, ultrasound",
author = "Valeria Nele and Schutt, {Carolyn E.} and Wojciechowski, {Jonathan P.} and Worrapong Kit-Anan and Doutch, {James J.} and Armstrong, {James P.K.} and Stevens, {Molly M.}",
note = "Funding Information: V.N. acknowledges support from the Ermenegildo Zegna Founder's Scholarship program and the Rosetrees Trust. J.P.K.A. was funded by Arthritis Research U.K. Foundation (21138) and the Medical Research Council (MR/S00551X/1). C.E.S. acknowledges support from the Whitaker International Program, Institute of International Education, United States of America. C.E.S. and M.M.S. acknowledge the grant from the UK Regenerative Medicine Platform “Acellular Approaches for Therapeutic Delivery” (MR/K026682/1). J.P.W. and M.M.S. were funded by the grant from the UK Regenerative Medicine Platform “Acellular / Smart Materials – 3D Architecture” (MR/R015651/1) and the Engineering and Physical Science Research Council (EPSRC) grant “Bio-functionalised nanomaterials for ultrasensitive biosensing” (EP/K020641/1). W.K.-A. and M.M.S. acknowledge support from British Heart Foundation Centre of Research Excellence (RE/13/4/30184). Experiments at the ISIS Neutron and Muon Source were supported by beamtime allocations from the Science and Technology Facilities Council (RB1810203). This work was benefited from the use of the SasView application, originally developed under NSF award DMR-0520547. SasView contains code developed with funding from the European Union's Horizon 2020 research and innovation programme under the SINE2020 project, grant agreement 654000. The authors acknowledge the use of microscopy facilities within the Harvey Flower Electron Microscopy Suite and the Facility for Imaging and Light Microscopy (FILM) at Imperial College London. Raw data is available at https://doi.org/10.5281/zenodo.3579225. Publisher Copyright: {\textcopyright} 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2020",
month = feb,
day = "1",
doi = "10.1002/adma.201905914",
language = "English (US)",
volume = "32",
journal = "Advanced Materials",
issn = "0935-9648",
publisher = "Wiley-VCH Verlag",
number = "7",
}