Imaging immune responses to implanted biomaterials

该博士项目将专注于改善器械植入部位周围炎症的临床前成像。主要方法将是通过设计、合成和应用新型MRI造影剂，这些造影剂可以靶向和报告急性和慢性炎症生物标志物。通过推进我们所掌握的成像工具，我们将能够实时无创地监测活体受试者的炎症病理。最初的重点将是临床前啮齿动物模型，以便通过监测不同材料/应用的影响来指导医疗器械的进一步开发。长期目标包括将其转化为临床，其潜在应用超出了植入物相关炎症。将探讨两种方法来应对这一挑战。第一种将依赖于基于纳米颗粒的MRI造影剂与炎症特异性抗体的偶联。这些药物可以局部或全身给药，并通过生物标志物识别选择性地积聚在炎症部位。明智地选择免疫反应生物标志物应该允许绘制炎症的各个阶段。第二种方法利用小分子MRI造影剂，报告器械植入周围的潜在生理状况。示例性目标包括pH和温度，这两者在免疫应答期间都发生了实质性改变。将同时进行更具侵入性的补充技术（例如电记录、组织学），以验证新技术和成像剂。

This PhD project will focus on improving preclinical imaging of inflammation around device implant sites. The primary method will be through the design, synthesis, and application of novel MRI contrast agents that can target and report on acute and chronic inflammation biomarkers. By advancing the imaging tools at our disposal, we will be able to non-invasively monitor inflammation pathology in living subjects in real-time. Initial focus will be on preclinical rodent models in order to guide further development of medical devices by monitoring the effects of different materials/applications. Long-term goals include translation to the clinic with potential applications beyond implant related inflammation. Two approaches will be explored to address this challenge. The first will rely on nanoparticle-based MRI contrast agents coupled to inflammation-specific antibodies. These agents can be topically or systemically administered and selectively accumulate at sites of inflammation via biomarker recognition. Judicious selection of immune-responsive biomarkers should allow various stages of inflammation to be mapped. The second approach utilises small molecule MRI contrast agents that report on the underlying physiological condition around device implantation. Example targets include pH and temperature, which are both substantially altered during the immune response. More invasive complimentary techniques (e.g. electrical recordings, histology) will be carried out in parallel to validate new techniques and imaging agents.