Development of the biologically active Guglielmi detachable coil for the treatment of cerebral aneurysms. Part II: an experimental study in a swine aneurysm model

Abstract

Background and purpose: Ion implantation is a surface-modification technology that creates a borderless surface on protein-coated platinum; this change in physical and chemical properties on the surface of Guglielmi detachable coils (GDCs) appears to enhance cell proliferation and adhesion. Our purpose was to evaluate the effect of ion implantation on GDCs in an experimental aneurysm model.

Methods: GDCs were coated with either type I collagen, fibronectin, vitronectin, laminin, or fibrinogen. Using He+ or Ne+ 1 x 10(14-15) ions/cm2, ion implantation was performed on these protein-coated GDCs (GDC-Is). A total of 56 experimental aneurysms were constructed microsurgically in the common carotid arteries of 28 swine. These experimental aneurysms were embolized with standard GDCs (n = 23), collagen GDC-Is (n = 11), vitronectin GDC-Is (n = 6), laminin GDC-Is (n = 4), fibrinogen GDC-Is (n = 6), and fibronectin GDC-Is (n = 6). The animals were sacrificed at day 14 after coil embolization. The physical properties of the new coils (friction on delivery, deployment into aneurysms, trackability, etc) and the development of tissue scarring and neoendothelium across the aneurysm's orifice were evaluated macroscopically and microscopically.

Results: No evidence of increased coil friction/stiffness was observed during delivery of GDC-Is through microcatheters in this aneurysm model. A more intense scar formation and neoendothelium at the neck of aneurysms were observed macroscopically when treated with GDC-Is. Significant differences in the proportion of neck coverage between standard GDCs (48.3% +/- 20.5%) and all GDC-I groups were observed (collagen GDC-I-89.4% +/- 14.9%, P < .01; vitronectin GDC-I-71.5% +/- 7.0%, P < .05; laminin GDC-I-76.5% +/- 11.0%, P < .05; fibrinogen GDC-I-74.8% +/- 13.9%, P < .05; fibronectin GDC-I-87.5% +/- 15.0%, P < .01). Light microscopy showed a well-organized fibrous tissue bridging the aneurysm's neck when using GDC-Is, whereas only a fibrin-like thin layer covered the standard GDC surfaces.

Conclusion: GDC-Is indicated a more intense inflammatory response in the aneurysm body and dome and faster re-endothelial coverage of the neck of the aneurysm. This accelerated histologic response may decrease the chances of coil compaction and aneurysm recanalization. This technology may improve anatomic and clinical outcomes in patients harboring intracranial aneurysms.

fig 1.

Scanning electron-microscopic appearances of surface of a standard coil (A) and a protein-coated ion-implanted coil (B) (original magnification, ×1500). Note crater-like appearance of ion-beam bombardment on protein-coated coil surface.

fig 2.

Angiograms of experimental aneurysms created on right and left common carotid arteries (A and B) and occluded aneurysms after standard GDC treatment (C, left) and protein coated GDC-I (D, right). Note tight packing of both aneurysms.

fig 3.

Macroscopic appearances of an aneurysmal orifice 14 days after treatment, with standard GDC (A) and collagen GDC-I (B). Surfaces of standard GDCs were covered with fibrin-like materials. On the other hand, the orifice of collagen GDC-I treated aneurysm was covered completely with thick fibrous tissue.

fig 4.

Neck coverage ratios for treated aneurysms at day 14. Largest dimensions of the orifice (OF) of the aneurysm and the fibrous membrane (FM) that covers the orifice were recorded and calculated as FM/OF proportion (fibrous membrane/ length of orifice × 100%). Standard GDC (n = 23), 48.3% ± 20.5%; collagen GDC-I (n = 11), 89.4% ± 14.9%; vitronectin GDC-I (n = 6), 71.5% ± 7.0%; laminin GDC-I (n = 4), 76.5% ± 11.0%; fibrinogen GDC-I, 74.8% ± 13.9% (n = 6); fibronectin GDC-I (n = 6), 87.5% ± 15.0%.

fig 5.

Light microscopic findings in region of aneurysm neck at day 14 after treatment, with standard GDCs (A, original magnification) or vitronectin GDC-Is (B, ×10). Note intense fibroblast response with vitronectin GDC-I. Only a thin fibrous layer was observed with standard GDCs. Light microscopic findings in region of the aneurysm sac. Sac of aneurysm treated with collagen GDC-I was filled with fibroblasts and monocytes. No neovascularization was seen with collagen GDC-Is (C, ×10), whereas microscopic neovascularization was seen in aneurysmal dome with standard GDCs (arrow, D, ×10).

fig 6.

Scanning electron microscopic appearance of orifice of embolized aneurysms. A and B, Lower (×20) and higher (×250) magnification of orifice treated with standard GDCs. Surface of coils were exposed to the arterial lumen and only fibrin/leukocyte complex was seen on surface. C and D, Lower (×23) and higher (×100) magnification of orifice treated with laminin GDC-Is. Orifice was covered completely with neoendothelial cell layer.