title: An injectable shear-thinning biomaterial for endovascular embolization.
abstract: Improved endovascular embolization of vascular conditions can generate better patient outcomes and minimize the need for repeat procedures. However, many embolic materials, such as metallic coils or liquid embolic agents, are associated with limitations and complications such as breakthrough bleeding, coil migration, coil compaction, recanalization, adhesion of the catheter to the embolic agent, or toxicity. Here, we engineered a shear-thinning biomaterial (STB), a nanocomposite hydrogel containing gelatin and silicate nanoplatelets, to function as an embolic agent for endovascular embolization procedures. STBs are injectable through clinical catheters and needles and have hemostatic activity comparable to metallic coils, the current gold standard. In addition, STBs withstand physiological pressures without fragmentation or displacement in elastomeric channels in vitro and in explant vessels ex vivo. In vitro experiments also indicated that STB embolization did not rely on intrinsic thrombosis as coils did for occlusion, suggesting that the biomaterial may be suitable for use in patients on anticoagulation therapy or those with coagulopathy. Using computed tomography imaging, the biomaterial was shown to fully occlude murine and porcine vasculature in vivo and remain at the site of injection without fragmentation or nontarget embolization. Given the advantages of rapid delivery, in vivo stability, and independent occlusion that does not rely on intrinsic thrombosis, STBs offer an alternative gel-based embolic agent with translational potential for endovascular embolization.
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
authors.forename: Reginald K
authors.initials: RK
authors.lastname: Avery
authors.affiliation: Department of Surgery, Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Albadawi
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Akbari
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Yu Shrike
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Duggan
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Dushyant V
authors.initials: DV
authors.lastname: Sahani
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Olsen
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA. alik@bwh.harvard.edu oklu.rahmi@mayo.edu.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.|Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.|Department of Physics, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Division of Engineering in Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02139, USA. alik@bwh.harvard.edu oklu.rahmi@mayo.edu.|Division of Vascular and Interventional Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Rahmi
authors.initials: R
authors.lastname: Oklu
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D057785:Catheters; D004621:Embolization, Therapeutic / Q000379:methods*; D057510:Endovascular Procedures; D006487:Hemostasis; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D007267:Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053761:Nanocomposites / Q000737:chemistry*; D012212:Rheology; D033081:Shear Strength; D017640:Silicates / Q000737:chemistry; D013552:Swine; D013927:Thrombosis; D014783:Viscosity
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D017640:Silicates