Release of basic fibroblast growth factor from acoustically-responsive scaffolds promotes therapeutic angiogenesis in the hind limb ischemia model

Hai Jin; Carole Quesada; Mitra Aliabouzar; Oliver D Kripfgans; Renny T Franceschi; Jianhua Liu; Andrew J Putnam; Mario L Fabiilli

doi:10.1016/j.jconrel.2021.09.013

Release of basic fibroblast growth factor from acoustically-responsive scaffolds promotes therapeutic angiogenesis in the hind limb ischemia model

J Control Release. 2021 Oct 10:338:773-783. doi: 10.1016/j.jconrel.2021.09.013. Epub 2021 Sep 14.

Authors

Hai Jin¹, Carole Quesada², Mitra Aliabouzar², Oliver D Kripfgans³, Renny T Franceschi⁴, Jianhua Liu⁵, Andrew J Putnam⁶, Mario L Fabiilli⁷

Affiliations

¹ Department of Medical Ultrasound, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China; Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
² Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
³ Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Applied Physics Program, University of Michigan, Ann Arbor, MI, USA.
⁴ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Dental School, University of Michigan, Ann Arbor, MI, USA.
⁵ Department of Medical Ultrasound, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
⁶ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
⁷ Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Applied Physics Program, University of Michigan, Ann Arbor, MI, USA. Electronic address: mfabiill@umich.edu.

Abstract

Pro-angiogenic growth factors have been studied as potential therapeutics for cardiovascular diseases like critical limb ischemia (CLI). However, the translation of these factors has remained a challenge, in part, due to problems associated with safe and effective delivery. Here, we describe a hydrogel-based delivery system for growth factors where release is modulated by focused ultrasound (FUS), specifically a mechanism termed acoustic droplet vaporization. With these fibrin-based, acoustically-responsive scaffolds (ARSs), release of a growth factor is non-invasively and spatiotemporally-controlled in an on-demand manner using non-thermal FUS. In vitro studies demonstrated sustained release of basic fibroblast growth factor (bFGF) from the ARSs using repeated applications of FUS. In in vivo studies, ARSs containing bFGF were implanted in mice following induction of hind limb ischemia, a preclinical model of CLI. During the 4-week study, mice in the ARS + FUS group longitudinally exhibited significantly more perfusion and less visible necrosis compared to other experimental groups. Additionally, significantly greater angiogenesis and less fibrosis were observed for the ARS + FUS group. Overall, these results highlight a promising, FUS-based method of delivering a pro-angiogenic growth factor for stimulating angiogenesis and reperfusion in a cardiovascular disease model. More broadly, these results could be used to personalize the delivery of therapeutics in different regenerative applications by actively controlling the release of a growth factor.

Keywords: Acoustic droplet vaporization; Angiogenesis; Basic fibroblast growth factor; Drug delivery; Fibrin; Hind limb ischemia; Phase-shift emulsion; Ultrasound.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Fibrin*
Fibroblast Growth Factor 2*
Hindlimb
Hydrogels
Ischemia / therapy
Mice
Neovascularization, Physiologic
Volatilization

Substances

Hydrogels
Fibroblast Growth Factor 2
Fibrin

Grants and funding

R01 HL139656/HL/NHLBI NIH HHS/United States