Development of a stent capable of the controlled release of basic fibroblast growth factor and argatroban to treat cerebral aneurysms: In vitro experiment and evaluation in a rabbit aneurysm model

• Published in: Journal of biomedical materials research. Part B, Applied biomaterials Applied biomaterials, 2019-08, Vol.107 (6), p.2185-2194
• Main Authors: Arai, Daisuke, Ishii, Akira, Ikeda, Hiroyuki, Abekura, Yu, Nishi, Hidehisa, Miyamoto, Susumu, Tabata, Yasuhiko
• Format: Article
• Language: English
• Subjects: Aneurysm; Anticoagulants; Argatroban; Biodegradability; Biodegradation; Biomedical materials; Carotid artery; cerebral aneurysm; Coatings; Connective tissues; Controlled release; Drug delivery systems; drug including stent; Elastase; endovascular treatment; Feasibility studies; Fibroblast growth factor 2; Fibroblasts; Gelatin; gelatin hydrogel; Growth factors; Hematoma; Hydrogels; Implants; Materials research; Materials science; Microspheres; PLGA microspheres; Polylactide-co-glycolide; Stents; Surgical implants; Thrombosis
• ISSN: 1552-4973; 1552-4981
• DOI: 10.1002/jbm.b.34314

An ideal stent to treat cerebral aneurysms should have an antithrombotic effect on the inner stent blood‐facing side and a tissue organization effect on the outer aneurysmal side of the stent. The objective of this study is to evaluate the feasibility of a drug containing stent in the in vivo treatment of cerebral aneurysms. Argatroban, an antithrombotic drug, is encapsulated in biodegradable poly (d,l‐lactide‐co‐glycolide) (PLGA) microspheres for the controlled release with an in vitro study conducted to evaluate the drug release and anticoagulation behavior of released drug. Basic fibroblast growth factor (bFGF), an organization drug, is released from gelatin hydrogels. The stents are coated with gelatin hydrogels incorporating bFGF and PLGA microspheres containing argatroban, and applied to the carotid artery aneurysm of an elastase‐induced rabbit model. Most of the aneurysm cavity is occupied by loose connective tissues in the group treated with drug‐coated stents, whereas extensive massive hematomas are observed in the group treated with drug‐free stents. The occurrence rate of in‐stent thrombus is small in the drug‐coated stents. The stent incorporating bFGF and PLGA microspheres containing argatroban is an effective device for cerebral aneurysm treatment. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2185–2194, 2019.