Norton L W, Koschwanez H E, Wisniewski N A, Klitzman B, Reichert W M
Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
J Biomed Mater Res A. 2007 Jun 15;81(4):858-69. doi: 10.1002/jbm.a.31088.
Vascular endothelial growth factor (VEGF) and dexamethasone (DX) release from hydrogel coatings were examined as a means to modify tissue inflammation and induce angiogenesis. Antibiofouling hydrogels for implantable glucose sensor coatings were prepared from 2-hydroxyethyl methacrylate, N-vinyl pyrrolidinone, and polyethylene glycol. Microdialysis sampling was used to test the effect of the hydrogel coating on glucose recovery. VEGF-releasing hydrogel-coated fibers increased vascularity and inflammation in the surrounding tissue after 2 weeks of implantation compared to hydrogel-coated fibers. DX-releasing hydrogel-coated fibers reduced inflammation compared to hydrogel-coated fibers and had reduced capsule vascularity compared to VEGF-releasing hydrogel-coated fibers. Hydrogels that released both VEGF and DX simultaneously also showed reduced inflammation at 2 weeks implantation; however, no enhanced vessel formation was observed indicating that the DX diminished the VEGF effect. At 6 weeks, there were no detectable differences between drug-releasing hydrogel-coated fibers and control fibers. From this study, hydrogel drug release affected initial events of the foreign body response with DX inhibiting VEGF, but once the drug depot was exhausted these effects disappeared.
研究了水凝胶涂层中血管内皮生长因子(VEGF)和地塞米松(DX)的释放情况,以此作为调节组织炎症和诱导血管生成的一种手段。用于可植入葡萄糖传感器涂层的抗生物污损水凝胶由甲基丙烯酸2-羟乙酯、N-乙烯基吡咯烷酮和聚乙二醇制备而成。采用微透析采样来测试水凝胶涂层对葡萄糖回收率的影响。与水凝胶涂层纤维相比,植入2周后,释放VEGF的水凝胶涂层纤维增加了周围组织的血管形成和炎症反应。与水凝胶涂层纤维相比,释放DX的水凝胶涂层纤维减轻了炎症,并且与释放VEGF的水凝胶涂层纤维相比,其包膜血管形成减少。同时释放VEGF和DX的水凝胶在植入2周时也显示出炎症减轻;然而,未观察到血管形成增强,这表明DX减弱了VEGF的作用。在6周时,药物释放水凝胶涂层纤维与对照纤维之间未检测到差异。从这项研究可知,水凝胶药物释放影响了异物反应的初始事件,其中DX抑制了VEGF,但一旦药物储存耗尽,这些影响就消失了。