RESUMO
OBJECTIVE: Current endovascular technology does not offer a perfect solution for all cerebral aneurysms. Our group has built two versions of a novel aneurysm intrasaccular occlusion device (AIOD) to address the drawbacks associated with current occlusion devices. The objective of the present study was to perform pilot proof of concept in vivo testing of this new AIOD in swine and canines. METHODS: Two configurations of the AIOD, termed 'coil-in-shell' and 'gel-in-shell', were implanted in surgically created sidewall aneurysms (n=4) in swine for acute occlusion studies, as well as sidewall (n=8) and bifurcation aneurysms (n=3) in canines to assess long term occlusion efficacy. Occlusion at all time points (immediate, 6 weeks, and 12â weeks) was evaluated by angiography. Neointimal healing at 12â weeks post-implantation in canines was examined histologically. RESULTS: Angiographic analysis showed that both the coil-in-shell and gel-in-shell devices achieved complete aneurysm occlusion immediately following device delivery in sidewall aneurysms in swine. In longer term canine studies, initial occlusion ranged from 71.3% to 100%, which was stable with no recurrence in any of the sidewall aneurysms at 6 or 12â weeks. Histological analysis at 12â weeks showed mature fibromuscular tissue at the neck of all aneurysms and no significant inflammatory response. CONCLUSIONS: The AIOD tested in this study showed promise in terms of acute and chronic occlusion of aneurysms. Our findings suggest that these devices have the potential to promote robust tissue healing at the aneurysm neck, which may minimize aneurysm recurrence. Although proof of principle has been shown, further work is needed to deliver this device through an endovascular route.
Assuntos
Embolização Terapêutica/normas , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Animais , Angiografia Cerebral , Cães , Embolização Terapêutica/tendências , SuínosRESUMO
Mechanical mismatch, along with inadequate hemocompatibility and endothelialization, contribute to the high failure rate of many synthetic vascular grafts. However, due to the dueling nature of these requirements (i.e., inhibiting platelet adhesion frequently means inhibiting endothelial cell (EC) adhesion), the creation of materials that simultaneously satisfy the mechanical and biological design criteria needed for small diameter vascular grafts has been an elusive goal. In this work, we demonstrate the ability of polyurethane (PU) containing hyaluronic acid (HA) in its backbone structure to reduce protein adsorption, platelet and bacterial adhesion, and fibroblast and macrophage proliferation while allowing the retention of both ECs and vascular-appropriate mechanics. Irrespective of HA molecular weight (MW), PU-HA materials selectively supported the growth of ECs relative to fibroblasts, reduced platelet adhesion, and performed comparably to negative controls with respect to bactericidal activity. The extent of EC growth on the PU-HA materials did differ with HA MW, with a lower HA MW yielding improved EC growth in both two-dimensional (2-D) films and 3-D electrospun fibrous scaffolds. These findings illustrate that HA incorporated into the backbone of a synthetic polymer structure can retain bioactivity, with subtle differences in HA MW significantly impacting the physical and biological properties of the biomaterial; in particular, PU modified with low-MW HA appears promising for vascular graft applications.
Assuntos
Células Endoteliais/citologia , Fibroblastos/citologia , Ácido Hialurônico/farmacologia , Macrófagos/citologia , Poliuretanos/farmacologia , Adsorção , Animais , Bovinos , Adesão Celular/efeitos dos fármacos , Comunicação Celular/efeitos dos fármacos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , DNA/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/ultraestrutura , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Teste de Materiais , Fenômenos Mecânicos , Camundongos , Peso Molecular , Células NIH 3T3 , Proteínas/metabolismo , Propriedades de Superfície , Alicerces Teciduais/química , Células U937RESUMO
The range of application of polyurethanes has been limited by their poor hemocompatibility and inability to resist non-specific binding of biomolecules and cells. In this work, a non-adhesive PU-based material was synthesized via the copolymerization of PU with dermatan sulfate. Incorporation of DS into the PU backbone dramatically increased material hydrophilicity and decreased protein adsorption. The in vitro adhesion of several cell types, including platelets, also significantly decreased with increasing DS content. Both the physical and biological properties of the DS contributed to the anti-adhesive properties of the PU/DS copolymer, and this anti-adhesive nature of PU/DS renders this new biomaterial attractive for blood-contacting or non-fouling applications.