Journal
BIOMATERIALS
Volume 75, Issue -, Pages 91-101Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.10.008
Keywords
Ultrasound response; Drug delivery; Biomaterials; Controlled release
Funding
- National Institutes of Health (NIH) [2 R01 DE013349]
- College of Engineering at the University of Rhode Island
- Rhode Island IDeA Network for Biomedical Research Excellence (RI-INBRE, NIH National Institute of General Medical Sciences) [2 P20 GM103430]
- Rhode Island Foundation [20144262]
- EPSCoR Track II grant from the National Science Foundation [1539068]
- Royal College of Surgeons' Office of Research and Innovation Seed Fund Award [GR 14-0963]
- Science Foundation Ireland (SFI) [SFI/12/RC/2278]
- European Union for a Marie Curie European Reintegration Grant [H2020, 659715]
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE013349] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM103430] Funding Source: NIH RePORTER
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In many biomedical contexts ranging from chemotherapy to tissue engineering, it is beneficial to sequentially present bioactive payloads. Explicit control over the timing and dose of these presentations is highly desirable. Here, we present a capsule-based delivery system capable of rapidly releasing multiple payloads in response to ultrasonic signals. In vitro, these alginate capsules exhibited excellent payload retention for up to 1 week when unstimulated and delivered their entire payloads when ultrasonically stimulated for 10-100 s. Shorter exposures (10 s) were required to trigger delivery from capsules embedded in hydrogels placed in a tissue model and did not result in tissue heating or death of encapsulated cells. Different types of capsules were tuned to rupture in response to different ultrasonic stimuli, thus permitting the sequential, on-demand delivery of nanoparticle payloads. As a proof of concept, gold nanoparticles were decorated with bone morphogenetic protein-2 to demonstrate the potential bioactivity of nanoparticle payloads. These nanoparticles were not cytotoxic and induced an osteogenic response in mouse mesenchymal stem cells. This system may enable researchers and physicians to remotely regulate the timing, dose, and sequence of drug delivery on-demand, with a wide range of clinical applications ranging from tissue engineering to cancer treatment. (C) 2015 Elsevier Ltd. All rights reserved.
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