Enhanced formation of fibrosis in a rabbit aneurysm by gelatin hydrogel incorporating basic fibroblast growth factor.
OBJECTIVE
This study was undertaken to analyze whether the controlled release of basic fibroblast growth factor (bFGF) can promote intrasaccular thrombosis in an experimental aneurysmal model.


METHODS
Carotid aneurysms were constructed in 80 rabbits with venous pouches and treated by placing gelatin hydrogels into each aneurysm incorporating 0, 25, 50, or 100 microg of bFGF or incorporating 100 microg of bFGF with different water contents. In the controls, the venous pouches either were not treated or were treated with gauze alone. Gelatin hydrogel was used for the controlled release of bFGF into the aneurysms. The formation of fibrosis in the aneurysms was histologically viewed to assess the area occupied by the fibrous tissues at 3 and 6 weeks after the hydrogel application. The effect of the bFGF dose and water content on obliterating the aneurysm by the hydrogels incorporating bFGF was also investigated.


RESULTS
Six weeks after the application of gelatin hydrogels with a water content of 95 wt% incorporating 100 microg of bFGF, the lateral pouch orifice was completely closed, obliterating the aneurysm at the level of tissue appearance, in contrast to hydrogels incorporating lower doses of bFGF and other control agents. The venous pouch aneurysm was histologically occupied with the newly formed fibrous tissue, and the fibrous tissue area and percentage of the aneurysmal lumen occupied by the fibrosis-gauze complex were significantly larger than those of other hydrogel applications (P < 0.05). The neointima tissue was homogeneously covered with a monolayer of Factor VIII-positive cells. The fact that there was no difference in the water content in the fibrosis formation induced by the bFGF-incorporated gelatin hydrogels indicated that the hydrogel biodegradability did not affect the obliteration of the aneurysm.


CONCLUSIONS
Local controlled release of bFGF stimulated the formation of in vivo fibrosis, resulting in obliteration of the aneurysm. The long-term results of the fibrous organization remain speculative.
Hong
L
L
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, 43 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Miyamoto
S
S
Yamada
K
K
Hashimoto
N
N
Tabata
Y
Y
D000818:Animals; D002339:Carotid Arteries / Q000473:pathology; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005355:Fibrosis; D005780:Gelatin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D002532:Intracranial Aneurysm / Q000473:pathology*; D011817:Rabbits; D017539:Tunica Intima / Q000473:pathology
D003692:Delayed-Action Preparations; D004343:Drug Implants; D016222:Fibroblast Growth Factor 2; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin