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

Abstract

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.

Recent Advances in Bioplastics: Application and Biodegradation

“…However, this composite induced diffuse foreign body reactions and granulocytic inflammations in porcine animal models, thereby posing a barrier for in vivo implantation [190]. Arai and colleagues [191] encapsulated basic fibroblast growth factor (bFGF) and agratroban in the PLGA coating of a metallic stent and tested it in a rabbit model to positively overcome the effect of an induced aneurysm. To the best of our knowledge, the only in vivo study of a prosthetic cardiac valve made of polyglycolic acid and polylactic acid in a 50:50 ratio was reported by Gottlieb and colleagues in a sheep model [192].…”

Endovascular Treatment of Ruptured Wide-Necked Anterior Communicating Artery Aneurysms Using a Low-Profile Visualized Intraluminal Support (LVIS) Device

“…The results showed that the majority of the aneurysm cavity was occupied by loose connective tissues in the drug-coated stent group, whereas extensive massive hematomas were observed in the drug-free stent group. Moreover, the drug-coated stents had a relatively low rate of instent thrombosis (30). However, the feasibility and safety of drugcoated stents for the treatment of human intracranial aneurysms still needs to be further explored.…”

Animal model contributes to the development of intracranial aneurysm: A bibliometric analysis

“…Arai et al developed a stent that can control the release of basic fibroblast growth factor (bFGF) and biodegradable poly(D,L-lactide-co-glycolide) (PLGA) argatroban to accelerate the recovery of an aneurysm in the elastase rabbit model. The authors found that the occurrence rate of an in-stent thrombus is low in drugcoated stents, which may be used in the clinic in future (68). In addition to developing new devices, animal models are more commonly used to study the biological mechanics of aneurysm formation.…”