title: Acceleration of aneurysm healing by P(DLLA-co-TMC)-coated coils enabling the controlled release of vascular endothelial growth factor.
abstract: Since the introduction of the detachable coil in endovascular treatment of intracranial aneurysms, the in-hospital mortality rate has been significantly decreased. Recurrence of the aneurysm remains the major drawback of using detachable coils. We prepared a bioactive coil coated with poly(d,l-lactide)-7co-(1,3-trimethylene carbonate) (P(DLLA-co-TMC)), a novel copolymer for controlling the release of vascular endothelial growth factor (VEGF). Platinum coils were prepared by successive coating with cationic P(DLLA-co-TMC) and anionic heparin. Then, recombinant human VEGF-165 (rhVEGF) was immobilized by affinity binding to heparin. The morphological characteristics and sustained in vitro release of rhVEGF were examined using scanning electron microscopy and enzyme-linked immunosorbent assay, respectively. The efficacy of these novel coils modified by P(DLLA-co-TMC)/rhVEGF was tested using a common carotid artery aneurysm model in rats. Experimental aneurysms were embolized with unmodified, P(DLLA-co-TMC)/heparin-coated or P(DLLA-co-TMC)/rhVEGF-coated platinum coils (n = 18). The coils were removed on days 15, 30 and 90 after insertion, and the histological and immunohistochemical analysis of factor VIII was performed to confirm the presence of endothelial cells in the organized area. In addition, the controlled in vivo release of VEGF was confirmed by Western blotting analysis. The release of VEGF tended to increase during the whole period and no burst release was observed. In the group treated with P(DLLA-co-TMC)/rhVEGF-coated platinum coils, clot organization and endothelial cell proliferation were accelerated. The immunohistochemistry study showed that the expression of factor VIII was found in the P(DLLA-co-TMC)/rhVEGF-coated coil group but not in the other two groups. Furthermore, Western blotting analysis confirmed that the major released VEGF in the aneurysm sac was from the P(DLLA-co-TMC)/VEGF-coated coil. P(DLLA-co-TMC)/rhVEGF-coated platinum coils can promote clot organization and endothelial cell proliferation in a rat aneurysm model.
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou 510282, Guangdong Province, People's Republic of China.
authors.forename: Qiujing
authors.initials: Q
authors.lastname: Wang
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Xinlin
authors.initials: X
authors.lastname: Sun
authors.forename: Bin
authors.initials: B
authors.lastname: Ji
authors.forename: Xubo
authors.initials: X
authors.lastname: Cui
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Zheng
authors.forename: Chengwei
authors.initials: C
authors.lastname: Chen
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Jiang
authors.forename: Aiping
authors.initials: A
authors.lastname: Zhu
authors.forename: Daping
authors.initials: D
authors.lastname: Quan
mesh_terms: D000783:Aneurysm / Q000473:pathology; D000818:Animals; D017536:Carotid Artery, Common / Q000473:pathology; D049109:Cell Proliferation; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D006493:Heparin / Q000737:chemistry; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000628:therapy*; D019344:Lactic Acid / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D020099:Coated Materials, Biocompatible; D011091:Polyesters; D011108:Polymers; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C121059:poly(lactide-co-trimethylene carbonate); D019344:Lactic Acid; C033616:poly(lactide); D005169:Factor VIII; D006493:Heparin