Fabrication of endothelialized capillary-like microchannel networks using sacrificial thermoresponsive microfibers.

In the body, capillary beds fulfill the metabolic needs of cells by acting as the sites of diffusive transport for vital gasses and nutrients. In artificial tissues, replicating the scale and complexity of capillaries has proved challenging, especially in a three-dimensional context. In order to better develop thick artificial tissues, it will be necessary to recreate both the form and function of capillaries.

mTG-Gelatin phantoms as standardized testbeds for skin biomechanical measurements with Myoton.

Quantitative assessment of skin mechanical properties can play a pivotal role in diagnosing and tracking various dermatological conditions. Myoton is a promising tool that rapidly and noninvasively measures five skin biomechanical parameters. Accurate interpretation of these parameters requires systematic in vitro testing with easy-to-fabricate, cost-effective skin-mimicking phantoms with controllable properties.

Microfluidic synthesis of radiotracers: recent developments and commercialization prospects.

Positron emission tomography (PET) is a powerful diagnostic tool that holds incredible potential for clinicians to track a wide variety of biological processes using specialized radiotracers. Currently, however, a single radiotracer accounts for over 95% of procedures, largely due to the cost of radiotracer synthesis. Microfluidic platforms provide a solution to this problem by enabling a dose-on-demand pipeline in which a single benchtop platform would synthesize a wide array of radiotracers.

Ectonucleoside triphosphate diphosphohydrolase-1 (CD39) impacts TGF-β1 responses: insights into cardiac fibrosis and function following myocardial infarction.

Extracellular purine nucleotides and nucleosides released from activated or injured cells influence multiple aspects of cardiac physiology and pathophysiology. Ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1; CD39) hydrolyzes released nucleotides and thereby regulates the magnitude and duration of purinergic signaling. However, the impact of CD39 activity on post-myocardial infarction (MI) remodeling is incompletely understood.

Leveraging the gel-to-sol transition of physically crosslinked thermoresponsive polymer hydrogels to enable reactions induced by lowering temperature.

Much work has been done on the use of heating to trigger reactions the temperature-dependent removal of a barrier or constraint separating reagents. Far less work, however, has been done on the use of cooling to achieve a similar goal. Numerous applications, such as those involving components or materials susceptible to persistent low temperatures and cases in which energy for heating is not available, would benefit from this inverse approach.

Rescuing the negative effects of aging in burn wounds using tacrolimus applied via microcapillary hydrogel dressing.

Introduction: Delays in treatment of burn injuries can lead to significant morbidity, loss of function, and poor aesthetic appearance. Preventing conversion from partial- to full-thickness burns may help mitigate these sequelae. The pathophysiology of burn wound conversion remains unknown, but an overactive immune response is thought to be implicated.

Successful prevention of secondary burn progression using infliximab hydrogel: A murine model.

Introduction: Burn injury remains a serious cause of morbidity and mortality worldwide. Severity of burns is determined by the percentage of burned area compared to the body surface area, age of patient, and by the depth of skin and soft tissue involvement; these factors determine management as well as prospective outcomes. The pathophysiology of partial- to full-thickness burn conversion remains poorly understood and is associated with a worse overall prognosis.

Rapid prototyping of cell culture microdevices using parylene-coated 3D prints.

Fabrication of microfluidic devices by photolithography generally requires specialized training and access to a cleanroom. As an alternative, 3D printing enables cost-effective fabrication of microdevices with complex features that would be suitable for many biomedical applications. However, commonly used resins are cytotoxic and unsuitable for devices involving cells.

Development of an N-Cadherin Biofunctionalized Hydrogel to Support the Formation of Synaptically Connected Neural Networks.

models of the human central nervous system (CNS), particularly those derived from induced pluripotent stem cells (iPSCs), are becoming increasingly recognized as useful complements to animal models for studying neurological diseases and developing therapeutic strategies. However, many current three-dimensional (3D) CNS models suffer from deficits that limit their research utility. In this work, we focused on improving the interactions between the extracellular matrix (ECM) and iPSC-derived neurons to support model development.

PRADA: Portable Reusable Accurate Diagnostics with nanostar Antennas for multiplexed biomarker screening.

Precise monitoring of specific biomarkers in biological fluids with accurate biodiagnostic sensors is critical for early diagnosis of diseases and subsequent treatment planning. In this work, we demonstrated an innovative biodiagnostic sensor, portable reusable accurate diagnostics with nanostar antennas (PRADA), for multiplexed biomarker detection in small volumes (~50 μl) enabled in a microfluidic platform. Here, PRADA simultaneously detected two biomarkers of myocardial infarction, cardiac troponin I (cTnI), which is well accepted for cardiac disorders, and neuropeptide Y (NPY), which controls cardiac sympathetic drive.

Spin∞: an updated miniaturized spinning bioreactor design for the generation of human cerebral organoids from pluripotent stem cells.

Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), have become a powerful system to study early development events and to model human disease. Cerebral organoids are generally produced in static culture or in a culture vessel with active mixing, and the two most widely used systems for mixing are a large spinning flask and a miniaturized multi-well spinning bioreactor (also known as Spin Omega (SpinΩ)). The SpinΩ provides a system that is amenable to drug testing, has increased throughput and reproducibility, and utilizes less culture media.

High-Yielding Radiosynthesis of [Ga]Ga-PSMA-11 Using a Low-Cost Microfluidic Device.

Purpose: Current PET radiotracer production models result in facility and operational costs that scale prohibitively with the number of tracers synthesized, particularly those made as a single dose-on-demand. Short of a paradigm shift in the technology and economics of radiotracer production, the impact of PET on precision medicine will be limited. Inexpensive, microfluidic radiochemistry platforms have the potential to significantly reduce costs associated with dose-on-demand production and expand the breadth of PET tracers accessible for molecular imaging.

Spatiotemporal Control of Morphogen Delivery to Pattern Stem Cell Differentiation in Three-Dimensional Hydrogels.

Morphogens are biological molecules that alter cellular identity and behavior across both space and time. During embryonic development, morphogen spatial localization can be confined to small volumes in a single tissue or permeate throughout an entire organism, and the temporal effects of morphogens can range from fractions of a second to several days. In most cases, morphogens are presented as a gradient to adjacent cells within tissues to pattern cell fate.

The relationship between the Young's modulus and dry etching rate of polydimethylsiloxane (PDMS).

Polydimethylsiloxane (PDMS) has been the pivotal materials for microfluidic technologies with tremendous amount of lab-on-a-chip devices made of PDMS microchannels. While molding-based soft-lithography approach has been extremely successful in preparing various PDMS constructs, some complex features have to been achieved through more complicated microfabrication techniques that involve dry etching of PDMS. Several recipes have been reported for reactive ion etching (RIE) of PDMS; however, the etch rates present large variations, even for the same etching recipe, which poses challenges in adopting this process for device fabrication.

Spatiotemporal control and modeling of morphogen delivery to induce gradient patterning of stem cell differentiation using fluidic channels.

The process of cell differentiation in a developing embryo is influenced by numerous factors, including various biological molecules whose presentation varies dramatically over space and time. These morphogens regulate cell fate based on concentration profiles, thus creating discrete populations of cells and ultimately generating large, complex tissues and organs. Recently, several in vitro platforms have attempted to recapitulate the complex presentation of extrinsic signals found in nature.

iPSC-Derived Brain Endothelium Exhibits Stable, Long-Term Barrier Function in Perfused Hydrogel Scaffolds.

There is a profound need for functional, biomimetic in vitro tissue constructs of the human blood-brain barrier and neurovascular unit (NVU) to model diseases and identify therapeutic interventions. Here, we show that induced pluripotent stem cell (iPSC)-derived human brain microvascular endothelial cells (BMECs) exhibit robust barrier functionality when cultured in 3D channels within gelatin hydrogels. We determined that BMECs cultured in 3D under perfusion conditions were 10-100 times less permeable to sodium fluorescein, 3 kDa dextran, and albumin relative to human umbilical vein endothelial cell and human dermal microvascular endothelial cell controls, and the BMECs maintained barrier function for up to 21 days.

Structural, functional, and behavioral insights of dopamine dysfunction revealed by a deletion in .

The human dopamine (DA) transporter (hDAT) mediates clearance of DA. Genetic variants in hDAT have been associated with DA dysfunction, a complication associated with several brain disorders, including autism spectrum disorder (ASD). Here, we investigated the structural and behavioral bases of an ASD-associated in-frame deletion in hDAT at N336 (∆N336).

Thermal transport in electrospun vinyl polymer nanofibers: effects of molecular weight and side groups.

Understanding and enhancing thermal transport in polymers is of great importance, and is necessary to enable next-generation flexible electronics, heat exchangers, and energy storage devices. Over the past several decades, significant enhancement of the thermal conductivity of polymeric materials has been achieved, but several key questions related to the effects of molecular structure on thermal transport still remain. By studying a series of electrospun vinyl polymer nanofibers, we investigate the relationship between thermal conductivity and both molecular chain length and side group composition.

Pulmonary Vascular Platform Models the Effects of Flow and Pressure on Endothelial Dysfunction in Associated Pulmonary Arterial Hypertension.

Endothelial dysfunction is a known consequence of bone morphogenetic protein type II receptor () mutations seen in pulmonary arterial hypertension (PAH). However, standard 2D cell culture models fail to mimic the mechanical environment seen in the pulmonary vasculature. Hydrogels have emerged as promising platforms for 3D disease modeling due to their tunable physical and biochemical properties.

A Customizable, Low-Cost Perfusion System for Sustaining Tissue Constructs.

The fabrication of engineered vascularized tissues and organs requiring sustained, controlled perfusion has been facilitated by the development of several pump systems. Currently, researchers in the field of tissue engineering require the use of pump systems that are in general large, expensive, and generically designed. Overall, these pumps often fail to meet the unique demands of perfusing clinically useful tissue constructs.

A simple microfluidic platform for rapid and efficient production of the radiotracer [F]fallypride.

Herein, we report the development of a simple, high-throughput and efficient microfluidic system for synthesizing radioactive [18F]fallypride, a PET imaging radiotracer widely used in medical research. The microfluidic chip contains all essential modules required for the synthesis and purification of radioactive fallypride. The radiochemical yield of the tracer is sufficient for multiple animal injections for preclinical imaging studies.

Modeling Neurovascular Disorders and Therapeutic Outcomes with Human-Induced Pluripotent Stem Cells.

The neurovascular unit (NVU) is composed of neurons, astrocytes, pericytes, and endothelial cells that form the blood-brain barrier (BBB). The NVU regulates material exchange between the bloodstream and the brain parenchyma, and its dysfunction is a primary or secondary cause of many cerebrovascular and neurodegenerative disorders. As such, there are substantial research thrusts in academia and industry toward building NVU models that mimic endogenous organization and function, which could be used to better understand disease mechanisms and assess drug efficacy.

Theranostic Gold Nanoantennas for Simultaneous Multiplexed Raman Imaging of Immunomarkers and Photothermal Therapy.

In this study, we demonstrate the theranostic capability of actively targeted, site-specific multibranched gold nanoantennas (MGNs) in triple-negative breast cancer (TNBC) cells in vitro. By utilizing multiplexed surface-enhanced Raman scattering (SERS) imaging, enabled by the narrow peak widths of Raman signatures, we simultaneously targeted immune checkpoint receptor programmed death ligand 1 (PDL1) and the epidermal growth factor receptor (EGFR) overexpressed in TNBC cells. A 1:1 mixture of MGNs functionalized with anti-PDL1 antibodies and Raman tag 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB) and MGNs functionalized with anti-EGFR antibodies and Raman tag -mercaptobenzoic acid (MBA) were incubated with the cells.

Composites Formed from Thermoresponsive Polymers and Conductive Nanowires for Transient Electronic Systems.

The disintegration of transient electronic systems after a preprogrammed time or a particular stimulus (e.g., water, light, or temperature) is fundamentally linked to the properties and behavior of the materials used for their construction.