Abstract
Hydrogels are commonly used for the delivery of bioactive molecules, especially growth
factors and cytokines capable of stimulating tissue regeneration. Regenerative processes
are regulated by the concentrations and spatiotemporal presentations of these molecules.
With conventional hydrogels, these critical delivery parameters cannot be actively
modulated after implantation. We have developed composite hydrogel scaffolds where
payload release is non-invasively modulated, in an on-demand manner, using ultrasound
(US). These acoustically-responsive scaffolds (ARSs) consist of a fibrin matrix doped
with a payload-carrying, perfluorocarbon (PFC) double emulsion. Previously, acoustic
droplet vaporization (ADV) was used to trigger release of a pro-angiogenic growth
factor, encapsulated in the ARS, which stimulated blood vessel formation in vivo. In the present study, we assess how characteristics of the monodispersed emulsion,
fibrin matrix, and US impact ADV thresholds and the release efficiency of a dextran
payload. ADV thresholds increased with the molecular weight of the PFC in the emulsion
and inversely with the volume fraction of emulsion in the ARS. Payload release from
ARSs with perfluoroheptane (C7) or perfluorooctane (C8) emulsions was dependent on
the number of z-planes of US used to generate ADV and inversely dependent on the lateral
spacing. Conversely, release from ARSs with perfluoropentane (C5) or perfluorohexane
(C6) emulsions was less dependent on these US exposure parameters. After ADV, payload
diffusion decreased significantly in ARSs with C5 or C6 emulsions compared with ARSs
with C7 or C8 emulsions. The expansion of the ARS after ADV decreased with the molecular
weight of the PFC. Non-selective release increased with the molecular weight of the
PFC and thrombin concentration. Overall, these findings can be used for optimization
of ARS properties and US parameters in future therapeutic applications.
Key Words
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Article info
Publication history
Published online: June 22, 2019
Accepted:
May 22,
2019
Received in revised form:
May 16,
2019
Received:
November 19,
2018
Identification
Copyright
© 2019 World Federation for Ultrasound in Medicine & Biology. All rights reserved.
