Alginate for endovascular treatment of aneurysms and local growth factor delivery.
OBJECTIVE
Coil embolization is safe and effective but may be followed by aneurysm recurrence. Our purpose was to explore the use of alginate as a new embolic agent that could deliver growth factors and improve results of endovascular treatment of aneurysms.


METHODS
We first assessed the potential of alginate as a vector for growth factor delivery by using in vitro binding and elution studies. Lateral wall (n = 68) and bifurcation (n = 4) aneurysms were then constructed in six pigs and 36 dogs. We explored iodine-125 transforming growth factor-beta(1) in vivo alginate delivery in 16 canine aneurysms. We next assessed the effects of adding alginate to gelatin sponges on angiographic and pathologic results at 3 weeks (n = 4 each) in an established model used for the study of recanalization and recurrence. We then explored techniques to control endovascular alginate delivery without protection (n = 4), with the protection of a balloon (n = 4), and with the protection of a single coil (n = 12) at the aneurysm neck in 12 porcine aneurysms, four canine lateral wall aneurysms, and four canine bifurcation aneurysms. The stability of cross-linked alginate was studied after intraoperative injections in eight aneurysms. Finally, to determine the value of the material with or without growth factor in promoting aneurysm healing, we compared angiographic results and neointima formation 3 weeks after intraoperative embolization of canine lateral wall aneurysms with alginate blocks with or without platelet-derived growth factor-BB or transforming growth factor-beta(1) (n = 5 each).


RESULTS
Growth factors rapidly eluted from alginate in vitro and in vivo. Alginate coating of sponges led to improved angiographic results and thick neointima formation. Intraoperative alginate block embolization did not lead to recurrence, and growth factors delivered with alginate did not show added benefits. Endovascular alginate embolization was complicated by carotid emboli, and the polymer was unstable once injected, causing delayed neurologic deficits.


CONCLUSIONS
Growth factor delivery can be performed with alginate, but formulation changes and improved endovascular control are necessary before contemplating its use in intracranial aneurysms.
Raymond
Jean
J
Interventional Neuroradiology Laboratory, CHUM Research Center, Notre-Dame Hospital, 1560 Sherbrooke East, Suite M-8203, Montreal, Quebec, Canada H2L 4M1.
Metcalfe
Annick
A
Desfaits
Anne-Cecile
AC
Ribourtout
Edith
E
Salazkin
Igor
I
Gilmartin
Kevin
K
Embry
Gill
G
Boock
Robert J
RJ
D000464:Alginates; D000818:Animals; D021721:Balloon Occlusion / Q000379:methods*; D000077214:Becaplermin; D001672:Biocompatible Materials; D001682:Biological Availability; D002533:Cerebral Angiography; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004285:Dogs; D004337:Drug Carriers; D004621:Embolization, Therapeutic / Q000379:methods*; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007267:Injections; D002532:Intracranial Aneurysm / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020574:Proto-Oncogene Proteins c-sis; D013552:Swine; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000493:pharmacokinetics; D053773:Transforming Growth Factor beta1; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects
D000464:Alginates; D001672:Biocompatible Materials; D004337:Drug Carriers; D006603:Hexuronic Acids; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000077214:Becaplermin; D020723:Glucuronic Acid