Tunable Collagen Microfluidic Platform to Study Nanoparticle Transport in the Tumor Microenvironment.

This chapter describes the motivation and protocol for creating a perfused 3D microfluidic in vitro platform representative of the tumor microenvironment to study nanoparticle transport. The cylindrical vascularized tumor platform described consists of a central endothelialized microchannel surrounded by a collagen hydrogel matrix containing cancer cells. This system can be employed to investigate key nanoparticle transport events in the tumor such as extravasation, diffusion within the extracellular matrix, and nanoparticle uptake.

Docetaxel facilitates lymphatic-tumor crosstalk to promote lymphangiogenesis and cancer progression.

Background: Infiltration into lymphatic vessels is a critical step in breast cancer metastasis. Lymphatics undergo changes that facilitate metastasis as a result of activation of the cells lining lymphatic vessels, lymphatic endothelial cells (LECs). Inhibition of activation by targeting VEGFR3 can reduce invasion toward lymphatics.

In-Season Variations in Head Impact Exposure among Youth Football Players.

Head impact exposure (HIE) is often summarized by the total exposure measured during the season and does not indicate how the exposure was accumulated, or how it varied during the season. Therefore, the objective of this study was to compare HIE during pre-season, the first and second halves of the regular season, and playoffs in a sample of youth football players (n = 119, aged 9-13 years). Athletes were divided into one of four exposure groups based on quartiles computed from the distribution of risk-weighted cumulative exposure (RWE).

Environmental Toxin Screening Using Human-Derived 3D Bioengineered Liver and Cardiac Organoids.

Introduction: Environmental toxins, such as lead and other heavy metals, pesticides, and other compounds, represent a significant health concern within the USA and around the world. Even in the twenty-first century, a plethora of cities and towns in the U.S.

Allele-specific methylation in the genomic region in DNA from human saliva, CD4+ cells, and total leukocytes.

Background: Genetic variants within the fatty acid desaturase () gene cluster (human Chr11) are important regulators of long-chain (LC) polyunsaturated fatty acid (PUFA) biosynthesis in the liver and consequently have been associated with circulating LC-PUFA levels. More recently, epigenetic modifications such as DNA methylation, particularly within the cluster, have been shown to affect LC-PUFA levels. Our lab previously demonstrated strong associations of allele-specific methylation (ASM) between a single nucleotide polymorphism (SNP) rs174537 and CpG sites across the region in human liver tissues.

In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening.

Variability in patient response to anti-cancer drugs is currently addressed by relating genetic mutations to chemotherapy through precision medicine. However, practical benefits of precision medicine to therapy design are less clear. Even after identification of mutations, oncologists are often left with several drug options, and for some patients there is no definitive treatment solution.

Hyaluronan chemistries for three-dimensional matrix applications.

Hyaluronan is a ubiquitous constituent of mammalian extracellular matrices and, because of its excellent intrinsic biocompatibility and chemical modification versatility, has been widely employed in a multitude of biomedical applications. In this article, we will survey the approaches used to tailor hyaluronan to specific needs of tissue engineering, regenerative and reconstructive medicine and overall biomedical research. We will also describe recent examples of applications in these broader areas, such as 3D cell culture, bioprinting, organoid biofabrication, and precision medicine that are facilitated by the use of hyaluronan as a biomaterial.

Solubilized Amnion Membrane Hyaluronic Acid Hydrogel Accelerates Full-Thickness Wound Healing.

The early and effective treatment of wounds is vital to ensure proper wound closure and healing with appropriate functional and cosmetic outcomes. The use of human amnion membranes for wound care has been shown to be safe and effective. However, the difficulty in handling and placing thin sheets of membrane, and the high costs associated with the use of living cellularized tissue has limited the clinical application of amniotic membrane wound healing products.

Bioengineered Submucosal Organoids for In Vitro Modeling of Colorectal Cancer.

The physical nature of the tumor microenvironment significantly impacts tumor growth, invasion, and response to drugs. Most in vitro tumor models are designed to study the effects of extracellular matrix (ECM) stiffness on tumor cells, while not addressing the effects of ECM's specific topography. In this study, we bioengineered submucosal organoids, using primary smooth muscle cells embedded in collagen I hydrogel, which produce aligned and parallel fiber topography similar to those found in vivo.

Tissue-specific extracellular matrix promotes myogenic differentiation of human muscle progenitor cells on gelatin and heparin conjugated alginate hydrogels.

Unlabelled: Myogenic differentiation, cell fusion, and myotube formation of skeletal muscle progenitor cells (SMPCs) have key roles during skeletal muscle development and repair. However, after isolation from living tissue and transition to culture dishes, SMPCs gradually lose their function and stop propagating due to the absence of extracellular matrix (ECM). Despite encouraging results of experiments using ECM components in cell culture for maintenance and propagation of some tissue types, the benefits of this approach on SMPC culture are limited, because the bioactive molecules and proteins instantly release and are degraded during culture.

Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform.

Many drugs have progressed through preclinical and clinical trials and have been available - for years in some cases - before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues.

Neural Interaction Between Risk Sensitivity and Cognitive Control Predicting Health Risk Behaviors Among Late Adolescents.

The developmental period of adolescence is characterized by increasing incidence of health risk behaviors (HRBs). Based on theoretical models that emphasize the moderating role of cognitive control, this study examined how neural correlates of cognitive control and risk sensitivity interact to predict HRBs among late adolescents (17-20 years). Neuroimaging data indicate that risk-related hemodynamic activity in the anterior insula during anticipation of uncertain outcomes predicts HRBs among late adolescents exhibiting greater dorsal anterior cingulate cortex (dACC) activity during a cognitive interference task but not among late adolescents requiring less dACC activity.

A Comprehensive Characterization of Parameters Affecting High-Frequency Irreversible Electroporation Lesions.

Several focal therapies are being investigated clinically to treat tumors in which surgery is contraindicated. Many of these ablation techniques, such as radiofrequency ablation and microwave ablation, rely on thermal damage mechanisms which can put critical nerves or vasculature at risk. Irreversible electroporation (IRE) is a minimally invasive, non-thermal technique to destroy tumors.

Shoulder Strength Requirements for Upper Limb Functional Tasks: Do Age and Rotator Cuff Tear Status Matter?

Understanding upper limb strength requirements for daily tasks is imperative for early detection of strength loss that may progress to disability due to age or rotator cuff tear. We quantified shoulder strength requirements for 5 upper limb tasks performed by 3 groups: uninjured young adults and older adults, and older adults with a degenerative supraspinatus tear prior to repair. Musculoskeletal models were developed for each group representing age, sex, and tear-related strength losses.

Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform.

Glioblastoma (GBM) is one of most aggressive forms of brain cancer, with a median survival time of 14.6 months following diagnosis. This low survival rate could in part be attributed to the lack of model systems of this type of cancer that faithfully recapitulate the tumor architecture and microenvironment seen in vivo in humans.

Successful Treatment of Passive Fecal Incontinence in an Animal Model Using Engineered Biosphincters: A 3-Month Follow-Up Study.

Fecal incontinence (FI) is the involuntary passage of fecal material. Current treatments have limited successful outcomes. The objective of this study was to develop a large animal model of passive FI and to demonstrate sustained restoration of fecal continence using anorectal manometry in this model after implantation of engineered autologous internal anal sphincter (IAS) biosphincters.

Transplantation of a Human Tissue-Engineered Bowel in an Athymic Rat Model.

Intestinal failure is a serious clinical condition characterized by loss of motility, absorptive function, and malnutrition. Current treatments do not provide the optimal solution for patients due to the numerous resulting complications. A bioengineered bowel that contains the necessary cellular components provides a viable option for patients.

Optical Tracking and Digital Quantification of Beating Behavior in Bioengineered Human Cardiac Organoids.

Organoid and organ-on-a-chip technologies are rapidly advancing towards deployment for drug and toxicology screening applications. Liver and cardiac toxicities account for the majority of drug candidate failures in human trials. Liver toxicity generally produces liver cell death, while cardiac toxicity causes adverse changes in heart beat kinetics.

A feasibility study for enrichment of highly aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow.

A common problem with cancer treatment is the development of treatment resistance and tumor recurrence that result from treatments that kill most tumor cells yet leave behind aggressive cells to repopulate. Presented here is a microfluidic device that can be used to isolate tumor subpopulations to optimize treatment selection. Dielectrophoresis (DEP) is a phenomenon where particles are polarized by an electric field and move along the electric field gradient.

Solid-state nanopore localization by controlled breakdown of selectively thinned membranes.

We demonstrate precise positioning of nanopores fabricated by controlled breakdown (CBD) on solid-state membranes by spatially varying the electric field strength with localized membrane thinning. We show 100 × 100 nm precision in standard SiN membranes (30-100 nm thick) after selective thinning by as little as 25% with a helium ion beam. Control over nanopore position is achieved through the strong dependence of the electric field-driven CBD mechanism on membrane thickness.

Biomechanical properties of an implanted engineered tubular gut-sphincter complex.

Neuromuscular diseases of the gut alter the normal motility patterns. Although surgical intervention remains the standard treatment, preservation of the sphincter attached to the rest of the gut is challenging. The present study aimed to evaluate a bioengineered gut-sphincter complex following its subcutaneous implantation for 4 weeks in rats.

A finite element model of a six-year-old child for simulating pedestrian accidents.

Child pedestrian protection deserves more attention in vehicle safety design since they are the most vulnerable road users who face the highest mortality rate. Pediatric Finite Element (FE) models could be used to simulate and understand the pedestrian injury mechanisms during crashes in order to mitigate them. Thus, the objective of the study was to develop a computationally efficient (simplified) six-year-old (6YO-PS) pedestrian FE model and validate it based on the latest published pediatric data.

Selective Osmotic Shock (SOS)-Based Islet Isolation for Microencapsulation.

Islet transplantation (IT) has recently been shown to be a promising alternative to pancreas transplantation for reversing diabetes. IT requires the isolation of the islets from the pancreas, and these islets can be used to fabricate a bio-artificial pancreas. Enzymatic digestion is the current gold standard procedure for islet isolation but has lingering concerns.

Characterization of Irreversible Electroporation Ablation with a Validated Perfused Organ Model.

Purpose: To develop and validate a perfused organ model for characterizing ablations for irreversible electroporation (IRE)-based therapies.

Materials And Methods: Eight excised porcine livers were mechanically perfused with a modified phosphate-buffered saline solution to maintain viability during IRE ablation. IRE pulses were delivered using 2 monopolar electrodes over a range of parameters, including voltage (1,875-3,000 V), pulse length (70-100 µsec), number of pulses (50-600), electrode exposure (1.

Bioengineering the gut: future prospects of regenerative medicine.

Functions of the gastrointestinal tract include motility, digestion and absorption of nutrients. These functions are mediated by several specialized cell types including smooth muscle cells, neurons, interstitial cells and epithelial cells. In gastrointestinal diseases, some of the cells become degenerated or fail to accomplish their normal functions.