PCSK9 activation promotes early atherosclerosis in a vascular microphysiological system.

Atherosclerosis is a primary precursor of cardiovascular disease (CVD), the leading cause of death worldwide. While proprotein convertase subtilisin/kexin 9 (PCSK9) contributes to CVD by degrading low-density lipoprotein receptors (LDLR) and altering lipid metabolism, PCSK9 also influences vascular inflammation, further promoting atherosclerosis. Here, we utilized a vascular microphysiological system to test the effect of PCSK9 activation or repression on the initiation of atherosclerosis and to screen the efficacy of a small molecule PCSK9 inhibitor.

Nanotechnology for Pain Management: Current and Future Therapeutic Interventions.

Pain is one of the most common medical conditions and affects more Americans than diabetes, heart disease, and cancer combined. Current pain treatments mainly rely on opioid analgesics and remain unsatisfactory. The life-threatening side effects and addictive properties of opioids demand new therapeutic approaches.

Integrated Isogenic Human Induced Pluripotent Stem Cell-Based Liver and Heart Microphysiological Systems Predict Unsafe Drug-Drug Interaction.

Three-dimensional (3D) microphysiological systems (MPSs) mimicking human organ function are an emerging alternative to conventional monolayer cell culture and animal models for drug development. Human induced pluripotent stem cells (hiPSCs) have the potential to capture the diversity of human genetics and provide an unlimited supply of cells. Combining hiPSCs with microfluidics technology in MPSs offers new perspectives for drug development.

Advances in microphysiological blood-brain barrier (BBB) models towards drug delivery.

Though the blood-brain barrier (BBB) is vital for the maintenance of brain homeostasis, it also accounts for a high attrition rate of therapies targeting the central nervous system (CNS). The challenge of delivery across the BBB is attributed to a combination of low permeability through an endothelium closely knit by tight and adherens junctions, extremely low rates of endothelial transcytosis, and efflux transporters. In the past decade, enormous research efforts have been spent to develop BBB penetration strategies using biochemical or physical stimuli, aided by BBB-on-chips or microphysiological BBB models to facilitate in vitro studies.

OPENchip: an on-chip in situ molecular profiling platform for gene expression analysis and oncogenic mutation detection in single circulating tumour cells.

Liquid biopsy holds promise towards practical implementation of personalized theranostics of cancer. In particular, circulating tumour cells (CTCs) can provide clinically actionable information that can be directly linked to prognosis or therapy decisions. In this study, gene expression patterns and genetic mutations in single CTCs are simultaneously analysed by strategically combining microfluidic technology and in situ molecular profiling technique.