Glucose Sensor/Tissue Interactions Engineering

葡萄糖传感器/组织相互作用工程

• 批准号: 6795359
• 负责人: FRANCIS MOUSSY
• 金额: $ 53.27万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6795359
• 关键词: CD44 molecule; angiogenesis; bioengineering /biomedical engineering; biomaterial compatibility; biosensor device; blood glucose; drug delivery systems; electrochemistry; fibrosis; gel; glucose transport; implant; inflammation; inhibitor /antagonist; laboratory rat; mathematical model; microcapsule; patient monitoring device; tissue /cell culture; tissue engineering; transfection; vascular endothelial growth factors

DESCRIPTION (provided by applicant): A major obstacle to the widespread application of implantable glucose sensors is that they progressively lose function after a relatively short period of time in vivo. This loss of function is in part a consequence of inflammation and fibrosis resulting from the tissue trauma caused by the sensor implantation and by reactions within the tissue. For an implantable glucose sensor, mere tissue toleration of the device is not sufficient; the sensor must also remain functional. It must be emphasize that although it is known that tissue reactions plays an important role in loss of sensor's function, the specific contribution of each tissue reactions (i.e. inflammation, fibrosis and loss of vasculature) has not yet been determined nor quantified. Furthermore, little work has been done so far on controlling these reactions to implanted biosensors. Based on the preceding information, we have developed the following hypotheses. Grant Hypotheses: We hypothesize that inflammation, fibrosis and loss of vasculature affect both the transport properties and the local concentration of glucose around the implanted sensor. As a result, implanted glucose sensors progressively lose function and become unreliable after implantation. We further hypothesize that our experiments and mathematical models will show that all three-tissue reactions play a significant role in the loss of sensor function. However, we also hypothesize that use of an anti-inflammatory drug delivery system, with an anti-fibrotic decorated surface hydrogel, and VEGF gene transfer can enhance the function and lifespan of the implanted sensors by decreasing inflammation and fibrosis, as well as by enhancing neovascularization. To test these hypotheses, we propose to use the current electrochemical Nation-based glucose sensor developed in our laboratory and all in vivo experiments will be conducted in the rat model. Therefore, the goals of this proposal will be: 1) to determine the specific contributions of inflammation, fibrosis and blood vessel density on the sensor's loss of function, using in vitro and in vivo studies as well as mathematical models, and 2) to control these reactions using a combination of approaches (decorated hydrogels, drug delivery and gene transfer) to enhance the glucose sensor's function and lifetime in vivo. Our overall goal for this proposal is to have a glucose sensor that can be implanted and provide reliable and continuous monitoring for at least 4 weeks.

描述（由申请人提供）：植入式葡萄糖传感器广泛应用的一个主要障碍是它们在体内相对较短的时间后逐渐丧失功能。这种功能丧失部分是由于传感器植入和组织内反应引起的组织创伤引起的炎症和纤维化的结果。 对于植入式葡萄糖传感器，仅装置的组织耐受性是不够的；传感器还必须保持功能。 必须强调的是，尽管已知组织反应在传感器功能丧失中起着重要作用，但每种组织反应（即炎症、纤维化和脉管系统丧失）的具体贡献尚未确定或量化。 此外，迄今为止，在控制植入生物传感器的这些反应方面几乎没有开展任何工作。 根据前面的信息，我们提出了以下假设。 格兰特假设：我们假设炎症、纤维化和脉管系统损失会影响植入传感器周围的转运特性和局部葡萄糖浓度。结果，植入的葡萄糖传感器在植入后逐渐丧失功能并且变得不可靠。我们进一步假设我们的实验和数学模型将表明所有三组织反应在传感器功能丧失中发挥着重要作用。然而，我们还假设使用具有抗纤维化装饰表面水凝胶的抗炎药物输送系统和 VEGF 基因转移可以通过减少炎症和纤维化以及增强植入传感器的功能和寿命来增强植入传感器的功能和寿命。新血管形成。为了检验这些假设，我们建议使用我们实验室开发的当前基于 Nation 的电化学葡萄糖传感器，并且所有体内实验都将在大鼠模型中进行。 因此，该提案的目标是：1）利用体外和体内研究以及数学模型来确定炎症、纤维化和血管密度对传感器功能丧失的具体贡献，2）控制这些反应结合使用多种方法（装饰水凝胶、药物递送和基因转移）来增强葡萄糖传感器的功能和体内寿命。 我们此提案的总体目标是拥有一个可以植入的葡萄糖传感器，并提供至少 4 周的可靠和连续监测。