Characterization of particle-endothelium interaction using particles functionalized with dual antibodies in a complex synthetic microvascular network (674.3)

The interaction between leukocytes and receptors on the endothelium play a key role in the early response to tissue injury. Research has shown that drug carrier particle rolling velocity increases dramatically with the increase of carrier size which affects their final attachment efficiency. The objective of this study is to characterize the rolling and adhesion profile of different size functionalized particles in a synthetic microvascular network (SMN). Functionalized particles were prepared by coating their surfaces with different ratios of antibodies against adhesion molecules ICAM‐1 and E‐selectin. Our modified Geographic Information System (GIS) approach was used to digitize the microvascular networks and generate the SMN on PDMS. The rolling velocity and adhesion profile of functionalized 2 & 10 µm particles was quantified in the SMN pre‐coated with TNF‐α activated human umbilical vein endothelial cells under shear conditions from 0 ‐ 280 sec‐1. Single antibody coated 10 µm particles roll at a higher speed than its 2 µm counterparts. Particle adhesion increased significantly with decreasing shear in SMNs. Increasing particle size from 2 µm to 10 µm did not change its binding efficiency significantly in SMNs, which is different from what have been reported in the traditional parallel plate flow channel. Particles functionalized with both a rolling molecule and an adhesion particle can more realistically mimic the leukocyte‐endothelium interaction in a SMN. These findings have important implications for better understanding the mechanisms behind inflammatory pathologies and for optimizing the design of carriers for targeted drug delivery. Grant Funding Source : Supported by Susan G. Komen for the Cure foundation