On-demand degradable embolic microspheres for immediate restoration of blood flow during image-guided embolization procedures

Hyunjun Choi; Bongseo Choi; Bo Yu; Weiguo Li; Monica M Matsumoto; Kathleen R Harris; Robert J Lewandowski; Andrew C Larson; Samdeep K Mouli; Dong-Hyun Kim

doi:10.1016/j.biomaterials.2020.120408

On-demand degradable embolic microspheres for immediate restoration of blood flow during image-guided embolization procedures

Biomaterials. 2021 Jan:265:120408. doi: 10.1016/j.biomaterials.2020.120408. Epub 2020 Sep 24.

Authors

Affiliations

¹ Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, 60607, USA.
² Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
³ Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, 60607, USA; Department of Biomedical Engineering, McCormick School of Engineering, Evanston, IL, 60208, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 60611, USA.
⁴ Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, 60607, USA; Department of Biomedical Engineering, McCormick School of Engineering, Evanston, IL, 60208, USA; Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 60611, USA. Electronic address: dhkim@northwestern.edu.

Abstract

Degradable embolic agents that provide transient arterial occlusion during embolization procedures have been of interest for many years. Ideally, embolic agents are visible with standard imaging modalities and offer on-demand degradability, permitting physicians to achieve desired arterial occlusion tailored to patient and procedure indication. Subsequent arterial recanalization potentially enhances the overall safety and efficacy of embolization procedures. Here, we report on-demand degradable and MRI-visible microspheres for embolotherapy. Embolic microspheres composed of calcium alginate and USPIO nanoclusters were synthesized with an air spray atomization and coagulation reservoir equipped with a vacuum suction. An optimized distance between spray nozzle and reservoir allowed uniform size and narrow size distribution of microspheres. The fabricated alginate embolic microspheres crosslinked with Ca²⁺ demonstrated highly responsive on-demand degradation properties in vitro and in vivo. Finally, the feasibility of using the microspheres for clinical embolization and recanalization procedures was evaluated with interventional radiologists in rabbits. Digital subtraction angiography (DSA) guided embolization of hepatic arteries with these embolic microspheres was successfully performed and the occlusion of artery was confirmed with DSA images and contrast enhanced MRI. T2 MRI visibility of the microspheres allowed to monitor the distribution of intra-arterial (IA) infused embolic microspheres. Subsequent on-demand image-guided recanalization procedures were also successfully performed with rapid degradation of microspheres upon intra-arterial infusion of an ion chelating agent. These instant degradable embolic microspheres will permit effective on-demand embolization/recanalization procedures offering great promise to overcome limitations of currently available permanent and biodegradable embolic agents.

Keywords: Embolic agents; Embolization; Embolotherapy; Interventional radiology; On-demand degradable microspheres.

Publication types

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

MeSH terms

Alginates
Animals
Arteries
Embolization, Therapeutic*
Humans
Magnetic Resonance Imaging
Microspheres
Rabbits

Substances

Alginates

Abstract

Publication types

MeSH terms

Substances

Grants and funding