Vallejo-Heligon Suzana G, Brown Nga L, Reichert William M, Klitzman Bruce
Department of Biomedical Engineering, Duke University, Durham, NC 27708-0281, United States.
Department of Biomedical Engineering, Duke University, Durham, NC 27708-0281, United States; Kenan Plastic Surgery Research Labs, Duke University Medical Center, Durham, NC 27710, United States.
Acta Biomater. 2016 Jan;30:106-115. doi: 10.1016/j.actbio.2015.10.045. Epub 2015 Oct 29.
Continuous glucose sensors offer the promise of tight glycemic control for insulin dependent diabetics; however, utilization of such systems has been hindered by issues of tissue compatibility. Here we report on the in vivo performance of implanted glucose sensors coated with Dexamethasone-loaded (Dex-loaded) porous coatings employed to mediate the tissue-sensor interface. Two animal studies were conducted to (1) characterize the tissue modifying effects of the porous Dex-loaded coatings deployed on sensor surrogate implants and (2) investigate the effects of the same coatings on the in vivo performance of Medtronic MiniMed SOF-SENSOR™ glucose sensors. The tissue response to implants was evaluated by quantifying macrophage infiltration, blood vessel formation, and collagen density around implants. Sensor function was assessed by measuring changes in sensor sensitivity and time lag, calculating the Mean Absolute Relative Difference (MARD) for each sensor treatment, and performing functional glucose challenge test at relevant time points. Implants treated with porous Dex-loaded coatings diminished inflammation and enhanced vascularization of the tissue surrounding the implants. Functional sensors with Dex-loaded porous coatings showed enhanced sensor sensitivity over a 21-day period when compared to controls. Enhanced sensor sensitivity was accompanied with an increase in sensor signal lag and MARD score. These results indicate that Dex-loaded porous coatings were able to elicit an attenuated tissue response, and that such tissue microenvironment could be conducive towards extending the performance window of glucose sensors in vivo.
In the present article, a coating to extend the functionality of implantable glucose sensors in vivo was developed. Our study showed that the delivery of an anti-inflammatory agent with the presentation of micro-sized topographical cues from coatings may lead to improved long-term glucose sensor function in vivo. We believe that improved function of sensors treated with the novel coatings was a result of the observed decreases in inflammatory cell density and increases in vessel density of the tissue adjacent to the devices. Furthermore, extending the in vivo functionality of implantable glucose sensors may lead to greater adoption of these devices by diabetic patients.
连续血糖传感器为胰岛素依赖型糖尿病患者提供了严格控制血糖的希望；然而，此类系统的应用受到组织相容性问题的阻碍。在此，我们报告了涂有载地塞米松（Dex）多孔涂层的植入式葡萄糖传感器的体内性能，该涂层用于调节组织 - 传感器界面。进行了两项动物研究，以（1）表征部署在传感器替代植入物上的多孔载Dex涂层的组织修饰作用，以及（2）研究相同涂层对美敦力MiniMed SOF - SENSOR™葡萄糖传感器体内性能的影响。通过量化植入物周围的巨噬细胞浸润、血管形成和胶原密度来评估组织对植入物的反应。通过测量传感器灵敏度和时间滞后的变化、计算每种传感器处理的平均绝对相对差异（MARD）以及在相关时间点进行功能性葡萄糖激发试验来评估传感器功能。用多孔载Dex涂层处理的植入物减少了炎症，并增强了植入物周围组织的血管化。与对照组相比，具有载Dex多孔涂层的功能性传感器在21天内显示出增强的传感器灵敏度。传感器灵敏度的提高伴随着传感器信号滞后和MARD评分的增加。这些结果表明，载Dex多孔涂层能够引发减弱的组织反应，并且这种组织微环境可能有助于延长葡萄糖传感器在体内的性能窗口。
在本文中，开发了一种用于延长可植入葡萄糖传感器体内功能的涂层。我们的研究表明，抗炎剂的递送以及涂层呈现的微观形貌线索可能导致体内长期葡萄糖传感器功能得到改善。我们认为，用新型涂层处理的传感器功能改善是由于观察到与设备相邻组织的炎症细胞密度降低和血管密度增加。此外，延长可植入葡萄糖传感器的体内功能可能会导致糖尿病患者更多地采用这些设备。
