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Biomaterials. 2017 Sep;140:26-36. doi: 10.1016/j.biomaterials.2017.06.012. Epub 2017 Jun 9.

Controlled release of basic fibroblast growth factor for angiogenesis using acoustically-responsive scaffolds.

Author information

1
Applied Physics Program, University of Michigan, Ann Arbor, MI, USA; Department of Radiology, University of Michigan Health System, Ann Arbor, MI, USA. Electronic address: ambaez@umich.edu.
2
Department of Radiology, University of Michigan Health System, Ann Arbor, MI, USA.
3
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; School of Dentistry, University of Michigan, Ann Arbor, MI, USA; Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, USA.
4
Applied Physics Program, University of Michigan, Ann Arbor, MI, USA; Department of Radiology, University of Michigan Health System, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
5
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
6
Applied Physics Program, University of Michigan, Ann Arbor, MI, USA; Department of Radiology, University of Michigan Health System, Ann Arbor, MI, USA.

Abstract

The clinical translation of pro-angiogenic growth factors for treatment of vascular disease has remained a challenge due to safety and efficacy concerns. Various approaches have been used to design spatiotemporally-controlled delivery systems for growth factors in order to recapitulate aspects of endogenous signaling and thus assist in translation. We have developed acoustically-responsive scaffolds (ARSs), which are fibrin scaffolds doped with a payload-containing, sonosensitive emulsion. Payload release can be controlled non-invasively and in an on-demand manner using focused, megahertz-range ultrasound (US). In this study, we investigate the in vitro and in vivo release from ARSs containing basic fibroblast growth factor (bFGF) encapsulated in monodispersed emulsions. Emulsions were generated in a two-step process utilizing a microfluidic device with a flow focusing geometry. At 2.5 MHz, controlled release of bFGF was observed for US pressures above 2.2 ± 0.2 MPa peak rarefactional pressure. Superthreshold US yielded a 12.6-fold increase in bFGF release in vitro. The bioactivity of the released bFGF was also characterized. When implanted subcutaneously in mice, ARSs exposed to superthreshold US displayed up to 3.3-fold and 1.7-fold greater perfusion and blood vessel density, respectively, than ARSs without US exposure. Scaffold degradation was not impacted by US. These results highlight the utility of ARSs in both basic and applied studies of therapeutic angiogenesis.

KEYWORDS:

Acoustic droplet vaporization; Angiogenesis; Basic fibroblast growth factor; Controlled release; Perfluorocarbon; Ultrasound

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