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Title: WE-AB-BRA-03: Non-Invasive Controlled Release from Implantable Hydrogel Scaffolds Using Ultrasound

Abstract

Purpose: To control release of a model payload in acoustically responsive scaffolds (ARSs) using focused ultrasound (FUS). Methods: Fluorescently-labeled dextran (10 kDa) was encapsulated in sonosensitive perfluorocarbon (C{sub 6}F{sub 14} or C{sub 5}F{sub 12}) double emulsions (mean diameter: 2.9±0.1 µm). For in vitro release studies, 0.5 mL ARSs (10 mg/mL fibrin, 1% (v/v) emulsion) were polymerized in 24 well plates and covered with 0.5 mL medium. Starting one day after polymerization, ARSs were exposed to FUS (2.5 MHz, Pr = 8 MPa, 13 cycles, 100 Hz PRF) for 2 min daily. The amount of dextran released into the media was quantified. For in vivo studies, 0.25 mL ARSs were prepared as described previously and injected subcutaneously in the lower back of BALB/c mice. After polymerization, a subset of the implanted ARSs were exposed to FUS (as previously described). Animals were imaged longitudinally using a fluorescence imaging system to quantify the amount of dextran released from the ARSs. Results: In vitro: Over 6 days, +FUS displayed an 8.2-fold increase in dextran release compared to −FUS (−FUS: 2.7±0.6%; +FUS: 22.2±3.0%) for C{sub 6}F{sub 14} ARSs, and a 6.7-fold increase (−FUS: 5.0±0.8%; +FUS: 38.5±1.6%) for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs. In vivo:more » +FUS displayed statistically greater dextran release compared to −FUS one day after implantation for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs (−FUS: 55.1±1.5%; +FUS: 74.1±2.2%) and three days after implantation for C{sub 6}F{sub 14} ARSs (−FUS: 1.4±6.5%; +FUS: 30.4±5.4%). Conclusion: FUS enables non-invasive control of payload release from an ARS, which could benefit growth factor delivery for tissue regeneration. ARS are versatile due to their tunability (i.e. stiffness, emulsion composition, FUS pressure, FUS frequency, etc.) and can be modified to for optimal payload release. Future work will optimize ARS formulations for in vivo use to minimize payload release in the absence of FUS. This work was supported by NIH Grant R21 AR065010 (M.L. Fabiilli) and the Basic Radiologic Sciences Innovative Research Award (M.L. Fabiilli). A. Moncion is supported by the National Science Foundation Graduate Student Research Fellowship (Grant DGE 1256260).« less

Authors:
; ; ; ;  [1]
  1. University of Michigan, Ann Arbor, MI (United States)
Publication Date:
OSTI Identifier:
22654094
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOMEDICAL RADIOGRAPHY; DEXTRAN; EMULSIONS; FLUORINE COMPOUNDS; GROWTH FACTORS; MHZ RANGE 01-100; PLANT GROWTH; PRESSURE RANGE MEGA PA; ULTRASONOGRAPHY

Citation Formats

Moncion, A, Kripfgans, O.D, Putnam, A.J, Frances chi, R.T, and Fabiilli, M.L. WE-AB-BRA-03: Non-Invasive Controlled Release from Implantable Hydrogel Scaffolds Using Ultrasound. United States: N. p., 2016. Web. doi:10.1118/1.4957732.
Moncion, A, Kripfgans, O.D, Putnam, A.J, Frances chi, R.T, & Fabiilli, M.L. WE-AB-BRA-03: Non-Invasive Controlled Release from Implantable Hydrogel Scaffolds Using Ultrasound. United States. doi:10.1118/1.4957732.
Moncion, A, Kripfgans, O.D, Putnam, A.J, Frances chi, R.T, and Fabiilli, M.L. Wed . "WE-AB-BRA-03: Non-Invasive Controlled Release from Implantable Hydrogel Scaffolds Using Ultrasound". United States. doi:10.1118/1.4957732.
@article{osti_22654094,
title = {WE-AB-BRA-03: Non-Invasive Controlled Release from Implantable Hydrogel Scaffolds Using Ultrasound},
author = {Moncion, A and Kripfgans, O.D and Putnam, A.J and Frances chi, R.T and Fabiilli, M.L},
abstractNote = {Purpose: To control release of a model payload in acoustically responsive scaffolds (ARSs) using focused ultrasound (FUS). Methods: Fluorescently-labeled dextran (10 kDa) was encapsulated in sonosensitive perfluorocarbon (C{sub 6}F{sub 14} or C{sub 5}F{sub 12}) double emulsions (mean diameter: 2.9±0.1 µm). For in vitro release studies, 0.5 mL ARSs (10 mg/mL fibrin, 1% (v/v) emulsion) were polymerized in 24 well plates and covered with 0.5 mL medium. Starting one day after polymerization, ARSs were exposed to FUS (2.5 MHz, Pr = 8 MPa, 13 cycles, 100 Hz PRF) for 2 min daily. The amount of dextran released into the media was quantified. For in vivo studies, 0.25 mL ARSs were prepared as described previously and injected subcutaneously in the lower back of BALB/c mice. After polymerization, a subset of the implanted ARSs were exposed to FUS (as previously described). Animals were imaged longitudinally using a fluorescence imaging system to quantify the amount of dextran released from the ARSs. Results: In vitro: Over 6 days, +FUS displayed an 8.2-fold increase in dextran release compared to −FUS (−FUS: 2.7±0.6%; +FUS: 22.2±3.0%) for C{sub 6}F{sub 14} ARSs, and a 6.7-fold increase (−FUS: 5.0±0.8%; +FUS: 38.5±1.6%) for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs. In vivo: +FUS displayed statistically greater dextran release compared to −FUS one day after implantation for C{sub 5}F{sub 12}:C{sub 6}F{sub 14} ARSs (−FUS: 55.1±1.5%; +FUS: 74.1±2.2%) and three days after implantation for C{sub 6}F{sub 14} ARSs (−FUS: 1.4±6.5%; +FUS: 30.4±5.4%). Conclusion: FUS enables non-invasive control of payload release from an ARS, which could benefit growth factor delivery for tissue regeneration. ARS are versatile due to their tunability (i.e. stiffness, emulsion composition, FUS pressure, FUS frequency, etc.) and can be modified to for optimal payload release. Future work will optimize ARS formulations for in vivo use to minimize payload release in the absence of FUS. This work was supported by NIH Grant R21 AR065010 (M.L. Fabiilli) and the Basic Radiologic Sciences Innovative Research Award (M.L. Fabiilli). A. Moncion is supported by the National Science Foundation Graduate Student Research Fellowship (Grant DGE 1256260).},
doi = {10.1118/1.4957732},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = {Wed Jun 15 00:00:00 EDT 2016},
month = {Wed Jun 15 00:00:00 EDT 2016}
}