A bio-instructive parylene-based conformal coating suppresses thrombosis and intimal hyperplasia of implantable vascular devices

Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to their surface lacking inherent functional endothelium. Here, inspired by the pathological mechanisms of vascular device failure and physiological functions of native endothelium, we developed a new generation of bioactive parylene (poly(p-xylylene))-based conformal coating to address these challenges of the vascular devices. This coating used a polyethylene glycol (PEG) linker to introduce an endothelial progenitor cell (EPC) specific binding ligand LXW7 (cGRGDdvc) onto the vascular devices for preventing platelet adhesion and selectively capturing endogenous EPCs. Also, we confirmed the long-term stability and function of this coating in human serum. Using two vascular disease-related large animal models, a porcine carotid artery interposition model and a porcine carotid artery-jugular vein arteriovenous graft model, we demonstrated that this coating enabled rapid generation of self-renewable “living” endothelium on the blood contacting surface of the expanded polytetrafluoroethylene (ePTFE) grafts after implantation. We expect this easy-to-apply conformal coating will present a promising avenue to engineer surface properties of “off-the-shelf” implantable vascular devices for long-lasting performance in the clinical settings.

Emerging risk factors for nonalcoholic fatty liver disease associated hepatocellular carcinoma

Worldwide,nonalcoholic fatty liver disease(NAFLD)has reached epidemic proportions and in parallel,hepatocellular carcinoma(HCC)has become one of the fastest growing cancers.Epidemiological studies have not only shed light on the prevalence and incidence of the disease but have also unmasked important environmental risk factors,including the role of diabetes and dyslipidemia in disease pathogenesis.Genetic association studies have identified single nucleotide polymorphisms implicated in NAFLD-HCC,many of which are part of lipid metabolism pathways.Through these clinical studies and subsequently,translational and basic research,the role of statins as a chemoprotective agent has also emerged with ongoing clinical trials assessing their utility in HCC prevention and treatment.In this review,we summarize the recent epidemiological studies describing the burden of NAFLD-HCC in different patient populations and countries.We discuss the genetic and environmental risk factors for NAFLD-HCC and highlight the chemoprotective role of statins and aspirin.We also summarize what is known about NAFLD-HCC in the cirrhosis and non-cirrhosis populations and briefly address the role of surveillance in NAFLD-HCC patients.

High-throughput physical phenotyping of cell differentiation

In this report,we present multiparameter deformability cytometry(m-DC),in which we explore a large set of parameters describing the physical phenotypes of pluripotent cells and their derivatives.m-DC utilizes microfluidic inertial focusing and hydrodynamic stretching of single cells in conjunction with high-speed video recording to realize high-throughput characterization of over 20 different cell motion and morphology-derived parameters.Parameters extracted from videos include size,deformability,deformation kinetics,and morphology.We train support vector machines that provide evidence that these additional physical measurements improve classification of induced pluripotent stem cells,mesenchymal stem cells,neural stem cells,and their derivatives compared to size and deformability alone.In addition,we utilize visual interactive stochastic neighbor embedding to visually map the high-dimensional physical phenotypic spaces occupied by these stem cells and their progeny and the pathways traversed during differentiation.This report demonstrates the potential of m-DC for improving understanding of physical differences that arise as cells differentiate and identifying cell subpopulations in a label-free manner.Ultimately,such approaches could broaden our understanding of subtle changes in cell phenotypes and their roles in human biology.

Shaped 3D microcarriers for adherent cell culture and analysis

Standard tissue culture of adherent cells is known to poorly replicate physiology and often entails suspending cells in solution for analysis and sorting,which modulates protein expression and eliminates intercellular connections.To allow adherent culture and processing in flow,we present 3D-shaped hydrogel cell microcarriers,which are designed with a recessed nook in a first dimension to provide a tunable shear-stress shelter for cell growth,and a dumbbell shape in an orthogonal direction to allow for self-alignment in a confined flow,important for processing in flow and imaging flow cytometry.We designed a method to rapidly design,using the genetic algorithm,and manufacture the microcarriers at scale using a transient liquid molding optofluidic approach.The ability to precisely engineer the microcarriers solves fundamental challenges with shear-stress-induced cell damage during liquid-handling,and is poised to enable adherent cell culture,in-flow analysis,and sorting in a single format.