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Background: This study aimed to deliver gellan sulfate core platinum coil with tenascin-C (GSCC-TNC) into rabbit side-wall aneurysms endovascularly and to evaluate the organization effects in a simulated clinical setting.Methods: Elastase-induced rabbit side-wall aneurysms were randomly coiled via a transfemoral route like clinical settings with platinum coils (PCs), gellan sulfate core platinum coils (GSCCs), or GSCC-TNCs (n = 5, respectively). Aneurysm-occlusion status was evaluated angiographically and histologically at 2 weeks post coiling. As each rabbit coiled aneurysm provided only 2-3 tissue slices due to technical limitations and prevented immunohistochemical evaluations, a PC, GSCC, or GSCC-TNC was randomly implanted in a rat blind-ended model (n = 3, respectively) and the organization effects were immunohistochemically evaluated for expressions of tenascin-C (TNC), transforming growth factor-beta (TGF-β), and matrix metalloproteinase-9 (MMP-9) 2 weeks later.Results: Coil handling was similar among the 3 kinds of coils. GSCCs showed a significantly higher ratio of organized area to the aneurysmal cavity than PCs, but GSCC-TNCs had the greatest organization-promoting effects on aneurysms (the ratio of organized area/aneurysmal luminal area: PC, 17.9 ± 7.1%; GSCC, 54.2 ± 18.3%; GSCC-TNC, 82.5 ± 5.8%). GSCC-TNCs had intense immunoreactivities for TNC, TGF-β, and MMP-9 in the organized thrombosis and tunica media. GSCCs also showed intense immunoreactivities for TNC, TGF-β, and MMP-9, although the extent was less than GSCC-TNCs. The immunoreactivities were hardly found in unorganized thrombus and the tunica media of aneurysm wall in the PC group.Conclusions: This study first showed that GSCC-TNCs promote intra-aneurysmal clot organization in simulated clinical settings using rabbits possibly through the TGF-β and MMP-9 upregulation. [ABSTRACT FROM AUTHOR]

The aims of this study were to develop a new coil, gellan sulfate core platinum coil (GSCC), that delivers tenascin-C (TNC) to an aneurysm (GSCC-TNC) and to evaluate the effects on intra-aneurysmal organization. We performed in vitro adsorption tests of TNC to gellan sulfate (GS). GSCC-TNC was produced by immersing GSCC in TNC solution under the following conditions (TNC concentration 10, 50, or 100 μg/mL; TNC immersion time 15, 30, or 60 min) by monitoring intra-aneurysmal organization in a rat blind-ended aneurysm model. In addition, 20 rats randomly underwent implantation of a platinum coil or the GSCC-TNC produced under optimum conditions into an aneurysm, whose organization effects were compared in a blind fashion at 2 weeks post-surgery. GS demonstrated a high affinity to TNC in a dose-dependent fashion (affinity constant = 1.79 × 10 (M)). GSCC immersed in 10 μg/mL of TNC solution for 30 and 60 min induced similar and better organization of aneurysmal cavity compared with that for 15 min (the ratio of the organized areas in an aneurysmal cavity-15 min, 27.2 ± 11.8 %; 30 min, 75.6 ± 11.9 %; 60 min, 82.6 ± 19.7 %, respectively) with the preservation of the aneurysmal wall structure, while higher TNC concentrations caused the destruction of the aneurysmal wall. GSCC-TNC produced under 10 μg/mL of TNC solution for 30 min showed a significantly better organization of aneurysms compared with bare platinum coils in rats. A newly developed coil, GSCC-TNC, may be effective for improving intra-aneurysmal organization after coil embolization. [ABSTRACT FROM AUTHOR]

Abstract: In this study, gellan sulfate (GS), a novel anticoagulant, was prepared by mixing deacetylated gellan and the dimethylformamide/sulfur trioxide (DMF-SO3) complex; this complex was prepared by adding varying volumes of chlorosulfonic acid (ClSO3H) to DMF. The anticoagulant properties of GS were measured by determining the coagulation time, prothrombin time (PT), and activated partial thromboplastin time (aPTT) of normal whole blood samples and by analyzing the activation of hemocoagulation factors V, VIII, IX, X, and XII. We found that 0.04mg/mL of GS with 40% sulfonation exhibits anticoagulant properties. GS selectively suppressed the activation of hemocoagulation factors XI and XII in the initial steps of the contact activation pathway. On the basis of our results, it can be concluded that the mechanism underlying the anticoagulation effects of GS was different from that of heparin. In addition, GS did not react with other hemocoagulation factors such as factors IX and X, and its activity was independent of antithrombin. [Copyright &y& Elsevier]

A new concept for cell-hybrid biomaterial is proposed in which human unbilical vein endothelial cells (HUVEC) are adhered to an immobilized gellan sulfate (GS) surface. Extra domain A containing fibronectin (EDA(+)FN) released from HUVEC is necessary for cell adhesion and multiplication. The material design in this study is based on these self-released cell adhesion proteins. The interaction between GS and EDA(+)FN was evaluated using the affinity constant (KA); the value obtained was 1.03×108 (M−1). These results suggest that the adhesion of HUVEC to GS may be supported by the adhesion of EDA(+)FN to GS. We also found that this new material adheres to HUVEC, allowing the reintroduction of EDA(+)FN, which is self-produced by the cell. This material is relatively easy to produce, not requiring the usual coating of adhesion proteins in pretreatment. [Copyright &y& Elsevier]