Imaging immune responses to implanted biomaterials

这个博士项目将专注于改善设备植入部位周围炎症的临床前成像。主要的方法将是通过设计、合成和应用新型磁共振造影剂，这些造影剂可以靶向和报告急性和慢性炎症生物标志物。通过改进我们掌握的成像工具，我们将能够非侵入性地实时监测活体受试者的炎症病理。最初的重点将放在临床前啮齿动物模型上，以通过监测不同材料/应用的效果来指导医疗器械的进一步发展。长期目标包括将其转化为临床应用，其潜在应用超出了植入物相关的炎症。将探索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偶联。这些药物可以局部或全身给药，并通过生物标记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记物应该可以绘制炎症的不同阶段。第二种方法使用小分子核磁共振造影剂，这种造影剂可以报告设备植入周围的潜在生理状况。例如，目标包括pH和温度，这两个指标在免疫反应期间都会发生重大变化。更具侵入性的补充技术(如电子记录、组织学)将同时进行，以验证新技术和显像剂。

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.