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Ingrowth of aorta wall into stent grafts impregnated with basic fibroblast growth factor: A porcine in vivo study of blood vessel prosthesis healing

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Author: Bas, J.M.A. van der · Quax, P.H.A. · Berg, A.C. van den · Visser, M.J.T. · Linden, E. van der · Bockel, J.H. van
Institution: TNO Preventie en Gezondheid
Source:Journal of Vascular Surgery, 4, 39, 850-858
Identifier: 280236
doi: doi:10.1016/j.jvs.2003.11.045
Keywords: Biology · Atropine · Basic fibroblast growth factor · Heparin · Isoflurane · Nitric oxide · Pancuronium bromide · Thiopental · Warfarin · Aneurysm surgery · Animal experiment · Animal tissue · Aorta prosthesis · Aorta wall · Blood vessel graft · Blood vessel prosthesis · Comparative study · Controlled study · Electron microscopy · Endoleak · Endovascular surgery · Nonhuman · Pathogenesis · Postoperative complication · Swine disease · Treatment outcome · Wound healing · Animals · Aorta · Blood Vessel Prosthesis · Blood Vessel Prosthesis Implantation · Coated Materials, Biocompatible · Collagen · Fibroblast Growth Factor 2 · Growth Substances · Heparin · Microscopy · Models, Animal · Myoblasts, Smooth Muscle · Polyethylene Terephthalates · Prosthesis Failure · Stents · Surgical Procedures, Minimally Invasive · Swine · Wound Healing


Objective: Endovascular aneurysm repair is an alternative treatment of abdominal aortic aneurysm. The procedure is less invasive, and morbidity and most probably mortality are reduced. However, some problems, such as endoleakage, are yet to be resolved. Endoleakage can occur after graft migration, as a result of insufficient fixation of the stent graft. One cause is deficient healing between the aortic neck and the stent graft. We hypothesize that better healing, achieved by induction of vascular cell ingrowth into the graft material, results in better graft fixation. Previously we demonstrated ingrowth of neointima into the graft material if the stent graft is impregnated with a coat of basic fibroblast growth factor (bFGF), heparin, and collagen. In this study we evaluated healing with bFGF-heparin-collagen-coated stent grafts in vivo. Methods: In 4 pigs, 32 endovascular stent grafts, manufactured from standard Dacron and Gianturco Z-stents, were placed in the aorta. The stent grafts were impregnated with either bFGF-heparin containing collagen (n = 16) or control collagen (n = 16). After 4 and 8 weeks animals were killed, and ingrowth and healing of the stent grafts were macroscopically and electron microscopically evaluated. Results: After 8 weeks all bFGF-impregnated stent grafts demonstrated ingrowth of tissue and healing between the graft and the aorta, whereas the control nonimpregnated stent grafts showed no ingrowth. Microscopic evaluation demonstrated α-smooth muscle actin-positive cells, most probably smooth muscle cells or myofibroblasts, growing from the vascular wall through the graft material. Conclusion: A Dacron prosthesis impregnated with collagen, heparin, and bFGF induced graft healing in an in vivo pig model, in contrast to nonimpregnated stent grafts. This in vivo study confirms our previous findings in vitro. These results indicate that healing between Dacron and the aorta can be achieved, and suggest that type I endoleakage may be resolved by inducing healing between the aortic wall and the prosthesis with graft material containing growth factor. Chemicals/CAS: atropine, 51-55-8, 55-48-1; basic fibroblast growth factor, 106096-93-9; collagen, 9007-34-5; heparin, 37187-54-5, 8057-48-5, 8065-01-8, 9005-48-5; isoflurane, 26675-46-7; nitric oxide, 10102-43-9; pancuronium bromide, 15500-66-0; thiopental, 71-73-8, 76-75-5; warfarin, 129-06-6, 2610-86-8, 3324-63-8, 5543-58-8, 81-81-2; Coated Materials, Biocompatible; Collagen, 9007-34-5; Fibroblast Growth Factor 2, 103107-01-3; Growth Substances; Heparin, 9005-49-6; Polyethylene Terephthalates