Embolization of a common carotid aneurysm with rhVEGF coupled to a pH-responsive chitosan in a rat model.
OBJECTIVE
Treatment of cerebral aneurysms by endovascular deployment of liquid embolic agents has been proposed as an alternative strategy to conventional coiling, and new materials are being developed for embolization. In this study, the authors used a single-injection, biocompatible, biodegradable and pH-responsive acrylated chitosan (aCHN) with conjugated vascular endothelial growth factor (rhVEGF) in a rat aneurysm model.


METHODS
The efficacy of the aCHN formulation with rhVEGF was tested using a common carotid artery occlusion model in rats, and the extent of embolization was evaluated using quantitative, qualitative, and histopathological techniques after 14 days of implantation.


RESULTS
The mean occlusion was significantly greater for the rhVEGF/aCHN-treated group (96.8 +/- 3.0%) than for the group receiving aCHN (74.7 +/- 5.6%) (p < 0.01). Through qualitative evaluation, intimal and medial proliferation were significantly greater with rhVEGF/aCHN than with aCHN and controls (p < 0.001). Degradation of the aCHN filler was monitored in concert with the production of extracellular matrix components. Macrophages migrated in and proliferated inside the occluded carotid artery lumens were identified by histological and immunostainings. Results showed resorption of chitosan with concurrent development of collagen and elastin into the vessel lumen, suggesting clot maturation into fibrosis.


CONCLUSIONS
Chitosan with a bioactive agent such as rhVEGF showed excellent results in occluding aneurysms in a rat model.
Pan
Hui
H
Department of Biomedical Engineering, State University of New York-Stony Brook, Stony Brook, New York 11794-8181, USA.
Zimmerman
Thomas
T
Zakhaleva
Julia
J
Abrahams
John M
JM
Jiang
Hongliang
H
Chen
Weiliam
W
D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D017536:Carotid Artery, Common / Q000473:pathology / Q000503:physiopathology; D048271:Chitosan / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D004621:Embolization, Therapeutic / Q000379:methods*; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D002532:Intracranial Aneurysm / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D008934:Mitogens / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use
D001672:Biocompatible Materials; D008934:Mitogens; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D004549:Elastin; D048271:Chitosan