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

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 (C6 F14 or C5 F12 ) 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 C6 F14 ARSs, and a 6.7-fold increase (-FUS: 5.0±0.8%; +FUS: 38.5±1.6%) for C5 F12 :C6 F14 ARSs. In vivo: +FUS displayed statistically greater dextran release compared to -FUS one day after implantation for C5 F12 :C6 F14 ARSs (-FUS: 55.1±1.5%; +FUS: 74.1±2.2%) and three days after implantation for C6 F14 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).