Human Mesofluidic Intestinal Model for Studying Transport of Drug Carriers and Bacteria Through a Live Mucosal Barrier.

The intestinal mucosal barrier forms a critical interface between lumen contents such as bacteria, drugs, and drug carriers and the underlying tissue. Current intestinal models, while recapitulating certain aspects of this barrier, generally present challenges with respect to imaging transport across mucus and uptake into enterocytes. A human mesofluidic small intestinal chip was designed to enable facile visualization of a mucosal interface created by growing primary human intestinal cells on a vertical hydrogel wall separating channels representing the intestinal lumen and circulatory flow.

A Strategic Blend of Stabilizing Polymers to Control Particle Surface Charge for Enhanced Mucus Transport and Cell Binding.

Mucus layers, viscoelastic gels abundant in anionic mucin glycoproteins, obstruct therapeutic delivery across all mucosal surfaces. We found that strongly positively charged nanoparticles (NPs) rapidly adsorb a mucin protein corona in mucus, impeding cell binding and uptake. To overcome this, we developed mucus-evading, cell-adhesive (MECS) NPs with variable surface charge using Flash NanoPrecipitation, by blending a neutral poly(ethylene glycol) (PEG) corona for mucus transport with a small amount, 5 wt%, of polycationic dimethylaminoethyl methacrylate (PDMAEMA) for increased cell targeting.

Using deep learning for dermatologist-level detection of suspicious pigmented skin lesions from wide-field images.

A reported 96,480 people were diagnosed with melanoma in the United States in 2019, leading to 7230 reported deaths. Early-stage identification of suspicious pigmented lesions (SPLs) in primary care settings can lead to improved melanoma prognosis and a possible 20-fold reduction in treatment cost. Despite this clinical and economic value, efficient tools for SPL detection are mostly absent.

Fully synthetic matrices for in vitro culture of primary human intestinal enteroids and endometrial organoids.

Epithelial organoids derived from human donor tissues are important tools in fields ranging from regenerative medicine to drug discovery. Organoid culture requires expansion of stem/progenitor cells in Matrigel, a tumor-derived extracellular matrix (ECM). An alternative completely synthetic ECM could improve reproducibility, clarify mechanistic phenomena, and enable human implantation of organoids.

OrgaQuant: Human Intestinal Organoid Localization and Quantification Using Deep Convolutional Neural Networks.

Organoid cultures are proving to be powerful in vitro models that closely mimic the cellular constituents of their native tissue. Organoids are typically expanded and cultured in a 3D environment using either naturally derived or synthetic extracellular matrices. Assessing the morphology and growth characteristics of these cultures has been difficult due to the many imaging artifacts that accompany the corresponding images.

Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies.

Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs - "4-way", "7-way", and "10-way" - each accommodating a mixing chamber and up to 4, 7, or 10 MPSs.

How do research faculty in the biosciences evaluate paper authorship criteria?

Authorship of peer-reviewed journal articles and abstracts has become the primary currency and reward unit in academia. Such a reward is crucial for students and postdocs who are often under-compensated and thus highly value authorship as an incentive. While numerous scientific and publishing organizations have written guidelines for determining author qualifications and author order, there remains much ambiguity when it comes to how these criteria are weighed by research faculty.

Postprandial lymphatic pump function after a high-fat meal: a characterization of contractility, flow, and viscosity.

Dietary lipids are transported from the intestine through contractile lymphatics. Chronic lipid loads can adversely affect lymphatic function. However, the acute lymphatic pump response in the mesentery to a postprandial lipid meal has gone unexplored.

S-Nitrosated Polypropylene Sulfide Nanoparticles for Thiol-Dependent Transnitrosation and Toxicity Against Adult Female Filarial Worms.

A synthetic polymer nanoparticle formulation utilizing the physiological nitrosothiol chemistry for nitric oxide delivery is shown. Toxicity of S-nitroso nanoparticles against adult female Brugia malayi worms, which are responsible for lymphatic filariasis, is dependent on nitric oxide release through transnitrosation as S-nitrosocysteine, a potent endogenous nitric oxide donor.

An integrated in vitro imaging platform for characterizing filarial parasite behavior within a multicellular microenvironment.

Lymphatic Filariasis, a Neglected Tropical Disease, is caused by thread-like parasitic worms, including B. malayi, which migrate to the human lymphatic system following transmission. The parasites reside in collecting lymphatic vessels and lymph nodes for years, often resulting in lymphedema, elephantiasis or hydrocele.

Minimally invasive method for determining the effective lymphatic pumping pressure in rats using near-infrared imaging.

The ability to quantify collecting vessel function in a minimally invasive fashion is crucial to the study of lymphatic physiology and the role of lymphatic pump function in disease progression. Therefore, we developed a highly sensitive, minimally invasive research platform for quantifying the pumping capacity of collecting lymphatic vessels in the rodent tail and forelimb. To achieve this, we have integrated a near-infrared lymphatic imaging system with a feedback-controlled pressure cuff to modulate lymph flow.

Dual-channel in-situ optical imaging system for quantifying lipid uptake and lymphatic pump function.

Nearly all dietary lipids are transported from the intestine to venous circulation through the lymphatic system, yet the mechanisms that regulate this process remain unclear. Elucidating the mechanisms involved in the functional response of lymphatics to changes in lipid load would provide valuable insight into recent implications of lymphatic dysfunction in lipid related diseases. Therefore, we sought to develop an in situ imaging system to quantify and correlate lymphatic function as it relates to lipid transport.

Sensitivity analysis of near-infrared functional lymphatic imaging.

Near-infrared imaging of lymphatic drainage of injected indocyanine green (ICG) has emerged as a new technology for clinical imaging of lymphatic architecture and quantification of vessel function, yet the imaging capabilities of this approach have yet to be quantitatively characterized. We seek to quantify its capabilities as a diagnostic tool for lymphatic disease. Imaging is performed in a tissue phantom for sensitivity analysis and in hairless rats for in vivo testing.