First 24-Hour-Long Intensive Care Unit Testing of a Clinical-Scale Microfluidic Oxygenator in Swine: A Safety and Feasibility Study.

Microfluidic membrane oxygenators are designed to mimic branching vasculature of the native lung during extracorporeal lung support. To date, scaling of such devices to achieve clinically relevant blood flow and lung support has been a limitation. We evaluated a novel multilayer microfluidic blood oxygenator (BLOx) capable of supporting 750-800 ml/min blood flow versus a standard hollow fiber membrane oxygenator (HFMO) in vivo during veno-venous extracorporeal life support for 24 hours in anesthetized, mechanically ventilated uninjured swine (n = 3/group).

Toward Efficient, Sustainable, and Scalable Methods of Treatment Characterization: An Investigation of Coding Clinical Practice from Chart Notes.

Purpose: Chart notes provide a low-cost data source that could help characterize what occurs in treatment with sufficient precision to improve management of care. This study assessed the interrater reliability of treatment content coded from chart notes and evaluated its concordance with content coded from transcribed treatment sessions.

Method: Fifty randomly selected and digitally recorded treatment events were transcribed and coded for practice content.

Effects of polydimethylsiloxane membrane surface treatments on human uterine smooth muscle cell strain response.

In the United States, 1 in 10 infants are born preterm. The majority of neonatal deaths and nearly a third of infant deaths are linked to preterm birth. Preterm birth is initiated when the quiescent state of the uterus ends prematurely, leading to contractions and parturition beginning as early as 32 weeks, though the origins are not well understood.

Fibroblast activation in response to TGFβ1 is modulated by co-culture with endothelial cells in a vascular organ-on-chip platform.

Tissue fibrosis is a major healthcare burden that affects various organs in the body for which no effective treatments exist. An underlying, emerging theme across organs and tissue types at early stages of fibrosis is the activation of pericytes and/or fibroblasts in the perivascular space. In hepatic tissue, it is well known that liver sinusoidal endothelial cells (EC) help maintain the quiescence of stellate cells, but whether this phenomenon holds true for other endothelial and perivascular cell types is not well studied.

Toward microfluidic integration of respiratory and renal organ support in a single cartridge.

Background: Extracorporeal organ assist devices provide lifesaving functions for acutely and chronically ill patients suffering from respiratory and renal failure, but their availability and use is severely limited by an extremely high level of operational complexity. While current hollow fiber-based devices provide high-efficiency blood gas transfer and waste removal in extracorporeal membrane oxygenation (ECMO) and hemodialysis, respectively, their impact on blood health is often highly deleterious and difficult to control. Further challenges are encountered when integrating multiple organ support functions, as is often required when ECMO and ultrafiltration (UF) are combined to deal with fluid overload in critically ill patients, necessitating an unwieldy circuit containing two separate cartridges.

Proteomic Profiling of Fallopian Tube-Derived Extracellular Vesicles Using a Microfluidic Tissue-on-Chip System.

The human fallopian tube epithelium (hFTE) is the site of fertilization, early embryo development, and the origin of most high-grade serous ovarian cancers (HGSOCs). Little is known about the content and functions of hFTE-derived small extracellular vesicles (sEVs) due to the limitations of biomaterials and proper culture methods. We have established a microfluidic platform to culture hFTE for EV collection with adequate yield for mass spectrometry-based proteomic profiling, and reported 295 common hFTE sEV proteins for the first time.

A Clinical-Scale Microfluidic Respiratory Assist Device with 3D Branching Vascular Networks.

Recent global events such as COVID-19 pandemic amid rising rates of chronic lung diseases highlight the need for safer, simpler, and more available treatments for respiratory failure, with increasing interest in extracorporeal membrane oxygenation (ECMO). A key factor limiting use of this technology is the complexity of the blood circuit, resulting in clotting and bleeding and necessitating treatment in specialized care centers. Microfluidic oxygenators represent a promising potential solution, but have not reached the scale or performance required for comparison with conventional hollow fiber membrane oxygenators (HFMOs).

Increased Local Testosterone Levels Alter Human Fallopian Tube mRNA Profile and Signaling.

Fallopian tube epithelium (FTE) plays a critical role in reproduction and can be the site where High Grade Serous Ovarian Carcinoma (HGSOC) originates. Tumorigenic oviductal cells, which are the murine equivalent of human fallopian tube secretory epithelial cells (FTSEC), enhance testosterone secretion by the ovary when co-cultured with the ovary, suggesting that testosterone is part of the signaling axis between the ovary and FTSEC. Furthermore, testosterone promotes proliferation of oviductal cells.

A high-throughput, 28-day, microfluidic model of gingival tissue inflammation and recovery.

Nearly half of American adults suffer from gum disease, including mild inflammation of gingival tissue, known as gingivitis. Currently, advances in therapeutic treatments are hampered by a lack of mechanistic understanding of disease progression in physiologically relevant vascularized tissues. To address this, we present a high-throughput microfluidic organ-on-chip model of human gingival tissue containing keratinocytes, fibroblast and endothelial cells.

Measurement of oxygen consumption rates of human renal proximal tubule cells in an array of organ-on-chip devices to monitor drug-induced metabolic shifts.

Measurement of cell metabolism in moderate-throughput to high-throughput organ-on-chip (OOC) systems would expand the range of data collected for studying drug effects or disease in physiologically relevant tissue models. However, current measurement approaches rely on fluorescent imaging or colorimetric assays that are focused on endpoints, require labels or added substrates, and lack real-time data. Here, we integrated optical-based oxygen sensors in a high-throughput OOC platform and developed an approach for monitoring cell metabolic activity in an array of membrane bilayer devices.

Characterization of main pulmonary artery and valve annulus region of piglets using echocardiography, uniaxial tensile testing, and a novel non-destructive technique.

Characterization of cardiovascular tissue geometry and mechanical properties of large animal models is essential when developing cardiovascular devices such as heart valve replacements. These datasets are especially critical when designing devices for pediatric patient populations, as there is often limited data for guidance. Here, we present a previously unavailable dataset capturing anatomical measurements and mechanical properties of juvenile Yorkshire (YO) and Yucatan (YU) porcine main pulmonary artery (PA) and pulmonary valve (PV) tissue regions that will inform pediatric heart valve design requirements for preclinical animal studies.

Versican secreted by the ovary links ovulation and migration in fallopian tube derived serous cancer.

High grade serous ovarian cancers (HGSOC) predominantly arise in the fallopian tube epithelium (FTE) and colonize the ovary first, before further metastasis to the peritoneum. Ovarian cancer risk is directly related to the number of ovulations, suggesting that the ovary may secrete specific factors that act as chemoattractants for fallopian tube derived tumor cells during ovulation. We found that 3D ovarian organ culture produced a secreted factor that enhanced the migration of FTE non-tumorigenic cells as well as cells harboring specific pathway modifications commonly found in high grade serous cancers.

Toward Development of a Higher Flow Rate Hemocompatible Biomimetic Microfluidic Blood Oxygenator.

The recent emergence of microfluidic extracorporeal lung support technologies presents an opportunity to achieve high gas transfer efficiency and improved hemocompatibility relative to the current standard of care in extracorporeal membrane oxygenation (ECMO). However, a critical challenge in the field is the ability to scale these devices to clinically relevant blood flow rates, in part because the typically very low blood flow in a single layer of a microfluidic oxygenator device requires stacking of a logistically challenging number of layers. We have developed biomimetic microfluidic oxygenators for the past decade and report here on the development of a high-flow (30 mL/min) single-layer prototype, scalable to larger structures via stacking and assembly with blood distribution manifolds.

High-throughput human primary cell-based airway model for evaluating influenza, coronavirus, or other respiratory viruses in vitro.

Influenza and other respiratory viruses present a significant threat to public health, national security, and the world economy, and can lead to the emergence of global pandemics such as from COVID-19. A barrier to the development of effective therapeutics is the absence of a robust and predictive preclinical model, with most studies relying on a combination of in vitro screening with immortalized cell lines and low-throughput animal models. Here, we integrate human primary airway epithelial cells into a custom-engineered 96-device platform (PREDICT96-ALI) in which tissues are cultured in an array of microchannel-based culture chambers at an air-liquid interface, in a configuration compatible with high resolution in-situ imaging and real-time sensing.

Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems.

Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. Uropathogenic (UPEC) accounts for a significant proportion of UTI, but a large number of other species can infect the urinary tract, each of which will have unique host-pathogen interactions with the bladder environment. Given the substantial economic burden of UTI and its increasing antibiotic resistance, there is an urgent need to better understand UTI pathophysiology - especially its tendency to relapse and recur.

A high-throughput microfluidic bilayer co-culture platform to study endothelial-pericyte interactions.

Microphysiological organ-on-chip models offer the potential to improve the prediction of drug safety and efficacy through recapitulation of human physiological responses. The importance of including multiple cell types within tissue models has been well documented. However, the study of cell interactions in vitro can be limited by complexity of the tissue model and throughput of current culture systems.

Comparison of Methods for Alcohol and Drug Screening in Primary Care Clinics.

Importance: Guidelines recommend that adult patients receive screening for alcohol and drug use during primary care visits, but the adoption of screening in routine practice remains low. Clinics frequently struggle to choose a screening approach that is best suited to their resources, workflows, and patient populations.

Objective: To evaluate how to best implement electronic health record (EHR)-integrated screening for substance use by comparing commonly used screening methods and examining their association with implementation outcomes.

High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows.

Drug development suffers from a lack of predictive and human-relevant in vitro models. Organ-on-chip (OOC) technology provides advanced culture capabilities to generate physiologically appropriate, human-based tissue in vitro, therefore providing a route to a predictive in vitro model. However, OOC technologies are often created at the expense of throughput, industry-standard form factors, and compatibility with state-of-the-art data collection tools.

The effectiveness of post-discharge navigation added to an inpatient addiction consultation for patients with substance use disorder; a randomized controlled trial.

It is unknown whether post-discharge navigation enhances the impact of hospital-initiated addiction care. This study tested the incremental benefit of telephonic linkage to a post-discharge navigator for patients who received an addiction consultation during hospitalization. A two-arm, randomized controlled trial of 395 hospitalized adults with substance use disorder who received an addiction consultation.

Exposure of human fallopian tube epithelium to elevated testosterone results in alteration of cilia gene expression and beating.

Study Question: How does exposure to a testosterone rich environment affect the function and gene expression of human fallopian tube epithelium (hFTE)?

Summary Answer: Elevated testosterone level alters several gene transcripts that regulate cilia expression and negatively impacts the rate of cilia beating.

What Is Known Already: The presence of estrogen in the follicular phase of the menstrual cycle increases the human fallopian tube ciliary beating frequency. The luteal phase, triggered by ovulation and increasing progesterone, is marked by a decrease in ciliary beating.

Correction: A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions.

Correction for 'A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions' by Kelly Tan et al., Lab Chip, 2019, 19, 1556-1566, DOI: .

Considerations for Treating Young People With Comorbid Autism Spectrum Disorder and Substance Use Disorder.

Although substance use disorder (SUD) and autism spectrum disorder (ASD) are highly comorbid with other mental disorders and commonly have onset during childhood, little attention has been paid to their overlap. Despite limited data suggesting that up to 4% of patients with ASD also have substance-related problems, there are no existing guidelines, protocols, or tailored resources focused on SUD in young people with co-occurring ASD. This is concerning given that the simultaneous presence of these disorders presents unique challenges that complicate clinical care.