Adhesion patterns in the microvasculature are dependent on bifurcation angle

Particle adhesion in vivo is highly dependent on the microvascular environment comprising of unique anatomical, geometrical, physiological fluid flow conditions and cell-particle and cell-cell interactions. Hence, proper design of vascular-targeted drug carriers that efficiently deliver therapeutics to the targeted cells or tissue at effective concentrations must account for these complex conditions observed in vivo. In this study, we build upon our previous results with the goal of characterizing the effects of bifurcations and their corresponding angle on adhesion of functionalized particles and neutrophils to activated endothelium. Our hypothesis is that adhesion is significantly affected by the type of biochemical interactions between particles and vessel wall as well as the presence of bifurcations and their corresponding angle. Here, we investigate adhesion of functionalized particles (2 mu m and 7 mu m microparticles) to protein coated channels as well as adhesion of human neutrophils to human endothelial cells under various physiological flow conditions in microfluidic bifurcating channels comprising of different contained angles (30 degrees, 60 degrees, 90 degrees, or 120 degrees). Our findings indicate that both functionalized particle and neutrophil adhesion propensity increase with a larger bifurcation angle. Moreover, the difference in the adhesion patterns of neutrophils and rigid, similar sized (7 mu m) particles is more apparent in the junction regions with a larger contained angle. By selecting the right particle size range, enhanced targeted binding of vascular drug carriers can be achieved along with a higher efficacy at optimal drug dosage. Hence, vascular drug particle design needs to be tailored to account for higher binding propensity at larger bifurcation angles. (C) 2015 Elsevier Inc. All rights reserved.