Coronary artery disease is a severe ischemic condition characterized by the reduction of blood flow in the arteries of the heart that results in the dysfunction and death of cardiac tissue. Despite research over several decades on how to reduce long-term complications and promote angiogenesis in the infarct, the medical field has yet to define effective treatments for inducing revascularization in the ischemic tissue. With this work, we have developed functional biomaterials for the controlled release of immunomodulatory cytokines to direct immune cell fate for controlling wound healing in the ischemic myocardium. The reparative effects of colony-stimulating factor (CSF-1), and anti-inflammatory interleukins 4/6/13 (IL4/6/13) have been evaluated in vitro and in a predictive in vivo model of ischemia (the skin flap model) to optimize a new immunomodulatory biomaterial that we use for treating infarcted rat hearts. Alginate hydrogels have been produced by internal gelation with calcium carbonate (CaCO 3) as carriers for the immunomodulatory cues, and their stability, degradation, rheological properties and release kinetics have been evaluated in vitro. CD14 positive human peripheral blood monocytes treated with the immunomodulatory biomaterials show polarization into pro-healing macrophage phenotypes. Unloaded and CSF-1/IL4 loaded alginate gel formulations have been implanted in skin flap ischemic wounds to test the safety and efficacy of the delivery system in vivo. Faster wound healing is observed with the new therapeutic treatment, compared to the wounds treated with the unloaded controls at day 14. The optimized therapy has been evaluated in a rat model of myocardial infarct (ischemia/reperfusion). Macrophage polarization toward healing phenotypes and global cardiac function measured with echocardiography and immunohistochemistry at 4 and 15 days demonstrate the therapeutic potential of the proposed immunomodulatory treatment in a clinically relevant infarct model.

The attenuation coefficient has proven to be a useful tool in numerous biological applications, but accurate calculation is dependent on the characterization of the confocal effect. This study presents a method to precisely determine the confocal effect and its focal plane within a sample by examining the ratio of two optical coherence tomography (OCT) images. The method can be employed to produce a single-value estimate, or a 2D map of the focal plane accounting for the curvature or tilt within the sample. Furthermore, this method is applicable to data obtained with both high numerical aperture (NA) and low-NA lenses, thereby furthering the applicability of the attenuation coefficient to high-NA OCT data. We test and validate this method using standard samples of Intralipid 20% and 5%, improving the accuracy to 99% from 65% compared to the traditional method and preliminarily show applicability to real biological data of glioblastoma acquired in vivo in a murine model.

Dynamic light scattering optical coherence microscopy (DLS-OCM) integrates DLS, which measures diffusion or flow of particles by analyzing fluctuations in light scattered by the particles, and OCM, which achieves single-cell resolution by combining coherence and confocal gating, integratively enabling cellular-resolution 3D mapping of the diffusion coefficient, and flow velocity. The diffusion coefficient mapping has a potential for the non-destructive measurement of cellular viability in the standard unit but has not been validated yet. Here, we present DLS-OCM imaging of intra-cellular motility (ICM) as a surrogate of cellular viability. For this purpose, we have simultaneously obtained and compared ICM-contrast DLS-OCM images and calcium fluorescence-contrast images of retinal ganglion cells, and then characterized the responses of the measured ICM to a change in cellular viability induced by environmental conditions such as temperature and pH. The diffusion-coefficient-represented ICM exhibits consistent changes with the manipulated cellular viability.

Optical coherence tomography angiography (OCTA) has emerged as an advanced in vivo imaging modality, which is widely used for the clinic ophthalmology and neuroscience research in the rodent brain cortex among others. Based on the high numerical aperture (NA) probing lens and the motion-corrected algorithms, a high-resolution imaging technique called OCT micro-angiography is applied to resolve the small blood capillary vessels ranging from 5[Formula: see text][Formula: see text]m to 10[Formula: see text][Formula: see text]m in diameter. As OCT-based techniques are recently evolving further from the structural imaging of capillaries toward spatio-temporal dynamic imaging of blood flow in capillaries, here we present a review on the latest techniques for the dynamic flow imaging. Studies on capillary blood flow using these techniques will help us better understand the roles of capillary blood flow for normal functioning of the brain as well as how it malfunctions in diseases.