POLYMERIC ELECTRON PARAMAGNETIC RESONANCE PROBES FOR REAL-TIME MONITORING OF TISSUE VASCULARIZATION

用于实时监测组织血管化的聚合物电子顺磁共振探头

• 批准号: 9811147
• 负责人: Jianjun Guan
• 金额: $ 15.42万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-08 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9811147
• 关键词: POLYMERIC; ELECTRON; PARAMAGNETIC; RESONANCE; PROBES

Program Director/Principal Investigator (Last, First, Middle): GUAN, JIANJUN Project Summary The objective of this proposal is to create bioeliminable and injectable hydrogel-based electron paramagnetic resonance (EPR) probes that can be implanted for the real-time and long-term measurement of tissue oxygen (O2) concentration. The purpose is to monitor the ischemic tissue vascularization process during therapy. Ischemic diseases, resulting from reduced blood supply, lead to serious damage and injury of various tissues and organs. The primary therapeutic goal for ischemic diseases is to vascularize the ischemic tissues to restore blood flow. To quickly, conveniently, and accurately evaluate the efficacy of the therapy, real-time and reproducible monitoring of tissue O2 concentration changes at the same tissue location by a minimally invasive or non-invasive spectroscopic approach represents a compelling strategy. However, this cannot be achieved by any clinically available approaches. Current approaches are either unable to provide real-time and long-term measurements under ischemic conditions or invasive. Among the different techniques for tissue O2 concentration measurement, EPR has the potential to achieve this goal. EPR has distinct advantages over other techniques, such as the ability to measure tissue O2 concentration without consuming O2, and to provide absolute values even at low O2 concentration environment. However, until now there is a lack of suitable EPR probes that can maintain a consistent concentration in tissues for an extended period (≥ 4 weeks), and can be implanted and/or retrieved by a minimally invasive approach. The proposed work addresses the critical need for bioeliminable, non-toxic, and long-lasting EPR probes that can be implanted by a minimally invasive approach for the long-term monitoring of tissue O2 concentration. This is highly novel and similar EPR probes have not been developed previously. The proposed hydrogel-based EPR probes will not only be injectable and bioeliminable, but also feature a fast gelation rate, a slow weight loss rate, high O2 permeability, and high EPR sensitivity. The injectable hydrogels can be implanted into tissues by a minimally invasive injection approach. The hydrogel-based EPR probes will have high molecular weight, and this will overcome the toxicity issue of commonly used small molecule EPR probes. Furthermore, they can be removed from the body after becoming water soluble by hydrolysis of side groups, thereby eliminating the need for retrieval. The hydrogels will be designed to have high gelation rate to achieve high retention in tissues. The probes with slow weight loss rate will maintain the EPR signal intensity for an extended period of time while retaining in a certain tissue location, allowing for long-term monitoring of O2 concentration. The high O2 permeability and EPR sensitivity will ensure that a small change in O2 concentration can be monitored in real-time. AIM #1 will create bioeliminable and injectable hydrogel-based EPR probes with a fast gelation rate, a slow weight loss rate, high oxygen permeability, and high EPR sensitivity. AIM #2 will test the hypothesis that the developed hydrogel-based EPR probe will allow continuous monitoring of tissue oxygen concentration using an ischemic limb model. OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) Page Continuation Format Page

项目总监/首席研究员（最后，第一，中间）：江恩 项目摘要 该提案的目的是创建可生物选择和可注射水凝胶的电子顺磁性 共振（EPR）问题可以用于实时和长期测量组织氧（O2）的问题（O2） 专注。目的是监测治疗过程中缺血性组织血管化过程。缺血性 疾病是由于血液供应减少而导致各种组织和器官的严重损害和伤害。 缺血性疾病的主要治疗目标是使缺血组织血管恢复血液流动。到 快速，方便，准确评估治疗的效率，实时和可再现的监测 组织O2浓度在同一组织位置通过微创或非侵入性光谱发生变化 方法代表了一种令人信服的策略。但是，这无法通过任何临床可用 方法。当前的方法要么无法提供实时和长期测量 缺血状况或侵入性。 在组织O2浓度测量的不同技术中，EPR有可能实现这一目标 目标。 EPR比其他技术具有明显的优势，例如测量组织O2浓度的能力 不消耗O2，即使在低O2浓度环境下也提供绝对值。但是，直到 现在缺乏合适的EPR问题，可以维持组织中的稳定浓度 周期（≥4周），可以通过微创方法植入和/或检索。 拟议的工作解决了对生物选择，无毒和持久的EPR问题的关键需求 可以通过最小侵入性的方法来植入组织O2浓度的长期监测。这是 高度新颖和类似的EPR问题以前尚未出现。拟议的基于水凝胶的EPR 问题不仅可以注射和生物限制，而且还具有快速的凝胶化率，减肥速度缓慢， 高O2渗透性和高EPR敏感性。可注射水凝胶可以通过A植入组织 微创注射方法。基于水凝胶的EPR探针将具有高分子量，这将 克服常用小分子EPR问题的毒性问题。此外，它们可以从 侧面的水解成为水固体后的身体，从而消除了检索的需求。 水凝胶将设计为具有高凝胶速率，以实现在组织中的高保留率。缓慢的问题 体重减轻率将在长时间内保持EPR信号强度，同时保留在一定的时间内 组织位置，可长期监测O2浓度。高O2渗透性和EPR敏感性 将确保可以实时监控O2浓度的少量变化。 AIM＃1将产生可生物限制和可注射水凝胶的EPR问题，并以快速的凝胶速率，缓慢 体重减轻率，高氧渗透性和高EPR敏感性。 AIM＃2将检验以下假设，即开发的基于水凝胶的EPR探针将允许连续监测 使用缺血性肢体模型的组织氧浓度。 OMB No. 0925-0001/0002（Rev. 08/12批准通过8/3​​1/2015）页面延续格式页面