Detection of atherosclerotic plaques with HDL-like porphyrin nanoparticles using an intravascular dual-modality optical coherence tomography and fluorescence system.

Atherosclerosis is the build-up of fatty plaques within blood vessel walls, which can occlude the vessels and cause strokes or heart attacks. It gives rise to both structural and biomolecular changes in the vessel walls. Current single-modality imaging techniques each measure one of these two aspects but fail to provide insight into the combined changes. To address this, our team has developed a dual-modality imaging system which combines optical coherence tomography (OCT) and fluorescence imaging that is optimized for a porphyrin lipid nanoparticle that emits fluorescence and targets atherosclerotic plaques. Atherosclerosis-prone apolipoprotein (Apo)e-/- mice were fed a high cholesterol diet to promote plaque development in descending thoracic aortas. Following infusion of porphyrin lipid nanoparticles in atherosclerotic mice, the fiber-optic probe was inserted into the aorta for imaging, and we were able to robustly detect a porphyrin lipid-specific fluorescence signal that was not present in saline-infused control mice. We observed that the nanoparticle fluorescence colocalized in areas of CD68+ macrophages. These results demonstrate that our system can detect the fluorescence from nanoparticles, providing complementary biological information to the structural information obtained from simultaneously acquired OCT.

Intravascular Imaging of Atherosclerosis by Using Engineered Nanoparticles.

Atherosclerosis is a leading cause of morbidity and mortality, and high-risk atherosclerotic plaques can result in myocardial infarction, stroke, and/or sudden death. Various imaging and sensing techniques (e.g., ultrasound, optical coherence tomography, fluorescence, photoacoustic) have been developed for scanning inside blood vessels to provide accurate detection of high-risk atherosclerotic plaques. Nanoparticles have been utilized in intravascular imaging to enable targeted detection of high-risk plaques, to enhance image contrast, and in some applications to also provide therapeutic functions of atherosclerosis. In this paper, we review the recent progress on developing nanoparticles for intravascular imaging of atherosclerosis. We discuss the basic nanoparticle design principles, imaging modalities and instrumentations, and common targets for atherosclerosis. The review is concluded and highlighted with discussions on challenges and opportunities for bringing nanoparticles into in vivo (pre)clinical intravascular applications.

Multiphasic scaffolds for the repair of osteochondral defects: Outcomes of preclinical studies.

Osteochondral defects are caused by injury to both the articular cartilage and subchondral bone within skeletal joints. They can lead to irreversible joint damage and increase the risk of progression to osteoarthritis. Current treatments for osteochondral injuries are not curative and only target symptoms, highlighting the need for a tissue engineering solution. Scaffold-based approaches can be used to assist osteochondral tissue regeneration, where biomaterials tailored to the properties of cartilage and bone are used to restore the defect and minimise the risk of further joint degeneration. This review captures original research studies published since 2015, on multiphasic scaffolds used to treat osteochondral defects in animal models. These studies used an extensive range of biomaterials for scaffold fabrication, consisting mainly of natural and synthetic polymers. Different methods were used to create multiphasic scaffold designs, including by integrating or fabricating multiple layers, creating gradients, or through the addition of factors such as minerals, growth factors, and cells. The studies used a variety of animals to model osteochondral defects, where rabbits were the most commonly chosen and the vast majority of studies reported small rather than large animal models. The few available clinical studies reporting cell-free scaffolds have shown promising early-stage results in osteochondral repair, but long-term follow-up is necessary to demonstrate consistency in defect restoration. Overall, preclinical studies of multiphasic scaffolds show favourable results in simultaneously regenerating cartilage and bone in animal models of osteochondral defects, suggesting that biomaterials-based tissue engineering strategies may be a promising solution.