Ultrasound-triggered enzymatic gelation
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Hydrogels are formed using various triggers, including light irradiation, pH adjustment, heating,
cooling or chemical addition. In this report, 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 our knowledge, these results are the first instance in which ultrasound has been used as a
trigger for either enzyme catalysis or enzymatic hydrogelation. This approach is highly versatile and
Peer reviewed version of the manuscript published in final form at Advanced Materials (2020)
2
could 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.
cooling or chemical addition. In this report, 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 our knowledge, these results are the first instance in which ultrasound has been used as a
trigger for either enzyme catalysis or enzymatic hydrogelation. This approach is highly versatile and
Peer reviewed version of the manuscript published in final form at Advanced Materials (2020)
2
could 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.
Date Issued
2020-02-20
Date Acceptance
2019-12-04
Citation
Advanced Materials, 2020, 32 (7), pp.1-8
ISSN
0935-9648
Publisher
Wiley
Start Page
1
End Page
8
Journal / Book Title
Advanced Materials
Volume
32
Issue
7
Copyright Statement
© 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Engineering & Physical Science Research Council (EPSRC)
British Heart Foundation
Arthritis Research UK
Medical Research Council
Identifier
https://onlinelibrary.wiley.com/doi/full/10.1002/adma.201905914
Grant Number
MR/S00551X/1
MR/R015651/1
EP/K020641/1
RE/13/4/30184
21138
MR/S00551X/1
Subjects
Science & Technology
Physical Sciences
Technology
Chemistry, Multidisciplinary
Chemistry, Physical
Nanoscience & Nanotechnology
Materials Science, Multidisciplinary
Physics, Applied
Physics, Condensed Matter
Chemistry
Science & Technology - Other Topics
Materials Science
Physics
enzymes
hydrogels
liposomes
microbubbles
ultrasound
DRUG-DELIVERY
CROSS-LINKING
TISSUE TRANSGLUTAMINASE
FOCUSED ULTRASOUND
LIPID VESICLES
HYDROGELS
MICROBUBBLES
RELEASE
LIPOSOMES
POLYSACCHARIDE
enzymes
hydrogels
liposomes
microbubbles
ultrasound
Nanoscience & Nanotechnology
02 Physical Sciences
03 Chemical Sciences
09 Engineering
Publication Status
Published
Date Publish Online
2020-01-10