Image-based crosstalk analysis of cell-cell interactions during sprouting angiogenesis using blood-vessel-on-a-chip.

BACKGROUND: Sprouting angiogenesis is an important mechanism for morphogenetic phenomena, including organ development, wound healing, and tissue regeneration. In regenerative medicine, therapeutic angiogenesis is a clinical solution for recovery from ischemic diseases. Mesenchymal stem cells (MSCs) have been clinically used given their pro-angiogenic effects. MSCs are reported to promote angiogenesis by differentiating into pericytes or other vascular cells or through cell-cell communication using multiple protein-protein interactions. However, how MSCs physically contact and move around ECs to keep the sprouting angiogenesis active remains unknown. METHODS: We proposed a novel framework of EC-MSC crosstalk analysis using human umbilical vein endothelial cells (HUVECs) and MSCs obtained from mice subcutaneous adipose tissue on a 3D in vitro model, microvessel-on-a-chip, which allows cell-to-tissue level study. The microvessels were fabricated and cultured for 10 days in a collagen matrix where MSCs were embedded. RESULTS: Immunofluorescence imaging using a confocal laser microscope showed that MSCs smoothed the surface of the microvessel and elongated the angiogenic sprouts by binding to the microvessel's specific microstructures. Additionally, three-dimensional modeling of HUVEC-MSC intersections revealed that MSCs were selectively located around protrusions or roots of angiogenic sprouts, whose surface curvature was excessively low or high, respectively. CONCLUSIONS: The combination of our microvessel-on-a-chip system for 3D co-culture and image-based crosstalk analysis demonstrated that MSCs are selectively localized to concave-convex surfaces on scaffold structures and that they are responsible for the activation and stabilization of capillary vessels.

Engineering Microneedles for Therapy and Diagnosis: A Survey.

Microneedle (MN) technology is a rising star in the point-of-care (POC) field, which has gained increasing attention from scientists and clinics. MN-based POC devices show great potential for detecting various analytes of clinical interests and transdermal drug delivery in a minimally invasive manner owing to MNs' micro-size sharp tips and ease of use. This review aims to go through the recent achievements in MN-based devices by investigating the selection of materials, fabrication techniques, classification, and application, respectively. We further highlight critical aspects of MN platforms for transdermal biofluids extraction, diagnosis, and drug delivery assisted disease therapy. Moreover, multifunctional MNs for stimulus-responsive drug delivery systems were discussed, which show incredible potential for accurate and efficient disease treatment in dynamic environments for a long period of time. In addition, we also discuss the remaining challenges and emerging trend of MN-based POC devices from the bench to the bedside.

Low-cost fabrication of a paper-based microfluidic using a folded pattern paper.

Despite that microfluidic paper-based analytical devices (µPADs) provide effective analytical platforms for point-of-care diagnosis in resource-limited areas, it remains challenging to achieve simple and low-cost fabrication of µPADs. A novel method for fabrication of µPADs is developed in this study using a folded polydimethylsiloxane (PDMS)-coated paper mask with a specific pattern to form a sandwich structure with inserted chromatographic paper. PDMS penetrates the target paper from the front and the back sides, and then is cured in the target paper to form legible channels. This method for prototyping µPADs has many favorable merits including simple operation without the need of trained personnel, fast fabrication and low cost. We further investigated colorimetric detection of melamine in the µPADs, and it showed a remarkable measurement with a detection limit of 0.1 ppm in aqueous solutions and liquid milk discriminated by the naked eye, which meets the detection limit required by USA and China. The fabricating strategy developed in this study is very promising and attractive for the development of simple µPADs for point-of-care applications, including diagnostic testing, food safety control and environmental monitoring.