Biocompatible Chemical Sensors via Nitric Oxide Release

通过一氧化氮释放的生物相容性化学传感器

• 批准号: 6671737
• 负责人: MARK E MEYERHOFF
• 金额: $ 22.65万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6671737
• 关键词: azo compounds; bioengineering /biomedical engineering; biomaterial compatibility; biomedical equipment development; biosensor device; biotechnology; blood chemistry; dogs; electrochemistry; electrolytes; enzyme linked immunosorbent assay; implant; laboratory rabbit; medical implant science; nitric oxide; patient monitoring device; platelet aggregation inhibitors; polymers; respiratory gas; slow release drug; spectrometry

To date, efforts to develop intravascular chemical sensors capable of accurate, real-time monitoring of clinically important blood gas (pH, PCO2, PO2) and electrolyte (e.g., K+, Ca++, etc.) levels within the blood of critically ill patients have failed owing to problems associated with the initiation of clotting on the sensors' surfaces as well as localized arterial constriction that diminishes blood flow at the implant site. The long term goal of this research is to explore and optimize the chemistries required to fabricate implantable electrochemical and optical blood gas and electrolyte sensors with outer polymeric films/membranes that slowly release low levels of nitric oxide (NO) locally, at the implant site. As demonstrated during the first phase of this new program, such in-situ release of NO prevents platelet adhesion/activation on the surface of the implanted sensors, and this leads to an improvement in the in vivo analytical performance of the devices. At the same time, preliminary data also points to the potential for the NO release to concomitantly dilate the artery immediately adjacent to the sensor, thereby maintaining good blood flow around the implanted sensor. The proposed Phase II studies will build upon significant progress made to date, especially with respect to the synthesis, characterization and in vivo evaluation of novel hydrophobic polymeric materials containing diazeniumdiolated species (either as additives or appended to the polymer backbone) that can release NO with fluxes at or above those generated by endothelial cells that line all normal blood vessels. Continued in vitro and in vivo biocompatibility testing of these new NO releasing silicone rubber, polyurethane and poly(vinyl chloride) materials will continue, as will efforts to understand the factors that control their storage stability and release rates of NO from these polymers under physiological conditions. Functional chemical sensors, both electrochemical and optical, will be prepared with the new NO release materials to determine the effect of local NO generation on the analytical performance of the devices (e.g., drift, selectivity, etc.). The in vivo analytical accuracy of an implanted electrochemical sensor for PO2, prepared with the various NO-release polymers, will be assessed (vs. control sensors w/o NO release in the same animals) using a canine model, to determine the effectiveness of local NO release on thrombogenicity and blood flow at the implant site. Finally, new exploratory studies will be initiated to examine the potential to utilize nitrosothiolated materials and chemical/biocatalytic nitrite reduction approaches as potential alternate strategies to the current diazeniumdiolate chemistry to formulate novel NO release hydrophobic polymers.

To date, efforts to develop intravascular chemical sensors capable of accurate, real-time monitoring of clinically important blood gas (pH, PCO2, PO2) and electrolyte (e.g., K+, Ca++, etc.) levels within the blood of critically ill patients have failed owing to problems associated with the initiation of clotting on the sensors' surfaces as well as localized arterial constriction that diminishes blood flow at the implant site. 这项研究的长期目标是使用外聚合物膜/膜在植入物位点探索和优化使用外聚合物膜/膜使用外聚合物膜/膜制造可植入的电化学和光学气体和电解质传感器所需的化学物质。 正如在该新程序的第一阶段所证明的那样，这种NO的原位释放可防止植入传感器表面上的血小板粘附/激活，这导致了设备的体内分析性能的改善。 同时，初步数据还表明，NO释放的潜力与传感器紧密相邻的动脉相同扩张，从而保持植入的传感器周围的良好血液流动。 拟议的II期研究将基于迄今为止取得的重大进展，尤其是在合成，表征和体内评估中，对包含重18zeniumdiolated物种的新型疏水聚合物材料（作为添加剂或附加到聚合物骨架上的添加剂或附加到聚合物骨架上），这些物质可以在所有正常血管内部或上层血管上都释放出磁通量或上方的磁通量。 持续的体外和体内生物相容性测试对这些新的NO释放有机硅橡胶，聚氨酯和聚氨酯和聚乙烯基含量（氯化乙烯基）材料将继续进行，这也将继续进行，以了解在生理条件下控制其从这些聚合物中控制其储存稳定性和释放速率的因素。电化学和光学的功能化学传感器将使用新的NO释放材料制备，以确定局部NO生成对设备分析性能的影响（例如，漂移，选择性等）。 使用犬模型，将评估使用各种无释放聚合物制备的PO2的植入的电化学传感器的体内分析精度（与各种无释放聚合物制备的PO2）（与同一动物中的​​控制传感器无释放），以确定当地NO在植入部位的血栓形成性和血流的有效性。最后，将启动新的探索性研究，以研究利用硝基硫醇化材料和化学/生物催化亚硝酸盐减少方法，作为当前饮食剂化学的潜在替代策略。