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Parametric Study of Acoustic Droplet Vaporization Thresholds and Payload Release From Acoustically-Responsive Scaffolds

  • Xiaofang Lu
    Affiliations
    Department of Radiology, University of Michigan Health System, Ann Arbor, USA
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  • Xiaoxiao Dong
    Affiliations
    Department of Radiology, University of Michigan Health System, Ann Arbor, USA

    Department of Ultrasound, Army Medical University, Chongqing, China
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  • Sam Natla
    Affiliations
    Department of Radiology, University of Michigan Health System, Ann Arbor, USA
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  • Oliver D. Kripfgans
    Affiliations
    Department of Radiology, University of Michigan Health System, Ann Arbor, USA

    Applied Physics Program, University of Michigan, Ann Arbor, USA

    Department of Biomedical Engineering, University of Michigan, Ann Arbor, USA
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  • J. Brian Fowlkes
    Affiliations
    Department of Radiology, University of Michigan Health System, Ann Arbor, USA

    Applied Physics Program, University of Michigan, Ann Arbor, USA

    Department of Biomedical Engineering, University of Michigan, Ann Arbor, USA
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  • Xueding Wang
    Affiliations
    Department of Radiology, University of Michigan Health System, Ann Arbor, USA

    Department of Biomedical Engineering, University of Michigan, Ann Arbor, USA
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  • Renny Franceschi
    Affiliations
    Department of Biomedical Engineering, University of Michigan, Ann Arbor, USA

    Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, USA

    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, USA
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  • Andrew J. Putnam
    Affiliations
    Department of Biomedical Engineering, University of Michigan, Ann Arbor, USA
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  • Mario L. Fabiilli
    Correspondence
    Address correspondence to: Mario Fabiilli, PhD, University of Michigan, 3226 A Medical Sciences Building I, 1301 Catherine Street, Ann Arbor, MI 48109-5667, USA.
    Affiliations
    Department of Radiology, University of Michigan Health System, Ann Arbor, USA

    Applied Physics Program, University of Michigan, Ann Arbor, USA

    Department of Biomedical Engineering, University of Michigan, Ann Arbor, USA
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      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.

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