Multi-Cell Type Glioblastoma Tumor Spheroids for Evaluating Sub-Population-Specific Drug Response.

Glioblastoma (GBM) is a lethal, incurable form of cancer in the brain. Even with maximally aggressive surgery and chemoradiotherapy, median patient survival is 14.5 months.

host-cell binding and invasion induces IL-8 and CXCL1 secretion that drives colorectal cancer cell migration.

is implicated in accelerating colorectal cancer (CRC) and is found within metastatic CRC cells in patient biopsies. Here, we found that bacterial invasion of CRC cells and cocultured immune cells induced a differential cytokine secretion that may contribute to CRC metastasis. We used a modified galactose kinase markerless gene deletion approach and found that invaded cultured HCT116 CRC cells through the bacterial surface adhesin Fap2.

Multi-Domain Photopatterned 3D Tumor Constructs in a Micro-Physiological System for Analysis, Quantification, and Isolation of Infiltrating Cells.

Cancer cell motility plays a central role in metastasis and tumor invasion but can be difficult to study accurately in vitro. A simple approach to address this challenge through the production of monolithic, photopatterned 3D tumor constructs in situ in a microfluidic device is described here. Through step-wise fabrication of adjoining hydrogel regions with and without incorporated cells, multidomain structures with defined boundaries are produced.

Functional restoration of ex vivo model of pylorus: Co-injection of neural progenitor cells and interstitial cells of Cajal.

Transplantation of neural stem cells is a promising approach in treatment of intestinal dysfunctionality. The interstitial cells of Cajal (ICCs) are also critical in conditions such as pyloric dysfunctionality and gastroparesis. The objective of this study was to replenish neurons and ICCs in a dysfunctional pylorus as cell-based therapy to restore functionality.

Immersion Bioprinting of Tumor Organoids in Multi-Well Plates for Increasing Chemotherapy Screening Throughput.

The current drug development pipeline takes approximately fifteen years and $2.6 billion to get a new drug to market. Typically, drugs are tested on two-dimensional (2D) cell cultures and animal models to estimate their efficacy before reaching human trials.

Probing prodrug metabolism and reciprocal toxicity with an integrated and humanized multi-tissue organ-on-a-chip platform.

Current drug development techniques are expensive and inefficient, partially due to the use of preclinical models that do not accurately recapitulate in vivo drug efficacy and cytotoxicity. To address this challenge, we report on an integrated, in vitro multi-organoid system that enables parallel assessment of drug efficiency and toxicity on multiple 3D tissue organoids. Built in a low-cost, adhesive film-based microfluidic device, these miniaturized structures require less than 200 µL fluid volume and are amenable to both matrix-based 3D cell culture and spheroid aggregate integration, each supported with an in situ photocrosslinkable hyaluronic acid hydrogel.

Using Low-Dimensional Manifolds to Map Relationships Between Dynamic Brain Networks.

As the field of dynamic brain networks continues to expand, new methods are needed to allow for optimal handling and understanding of this explosion in data. We propose here a novel approach that embeds dynamic brain networks onto a two-dimensional (2D) manifold based on similarities and differences in network organization. Each brain network is represented as a single point on the low dimensional manifold with networks of similar topology being located in close proximity.

Model of Patient-Specific Immune-Enhanced Organoids for Immunotherapy Screening: Feasibility Study.

Introduction: We hypothesized that engineering a combined lymph node/melanoma organoid from the same patient would allow tumor, stroma, and immune system to remain viable for personalized immunotherapy screening.

Methods: Surgically obtained matched melanoma and lymph node biospecimens from the same patient were transferred to the laboratory and washed with saline, antibiotic, and red blood cell lysis buffer. Biospecimens were dissociated, incorporated into an extracellular matrix (ECM)-based hydrogel system, and biofabricated into three dimensional (3D) mixed melanoma/node organoids.

Methods to measure, model and manipulate fluid flow in brain.

The brain consists of a complex network of cells and matrix that is cushioned and nourished by multiple types of fluids: cerebrospinal fluid, blood, and interstitial fluid. The movement of these fluids through the tissues has recently gained more attention due to implications in Alzheimer's Disease and glioblastoma. Therefore, methods to study these fluid flows are necessary and timely for the current study of neuroscience.

BioSphincters to treat Fecal Incontinence in Nonhuman Primates.

Loss of anorectal resting pressure due to internal anal sphincter (IAS) dysfunctionality causes uncontrolled fecal soiling and leads to passive fecal incontinence (FI). The study is focused on immediate and long-term safety and potential efficacy of bioengineered IAS BioSphincters to treat passive FI in a clinically relevant large animal model of passive FI. Passive FI was successfully developed in Non-Human Primates (NHPs) model.

Pleural Effusion Aspirate for use in 3D Lung Cancer Modeling and Chemotherapy Screening.

Lung cancer is the leading cause of cancer-related death worldwide yet disease models have been limited to traditional 2D culture utilizing cancer cell lines. In contrast, recently developed 3D models (organoids) have been adopted by researchers to improve the physiological relevance of laboratory study. We have hypothesized that 3D hydrogel-based models will allow for improved disease replication and characterization over standard 2D culture using cells taken directly from patients.

Development of a Concussion Risk Function for a Youth Population Using Head Linear and Rotational Acceleration.

Physical differences between youth and adults, which include incomplete myelination, limited neck muscle development, and a higher head-body ratio in the youth population, likely contribute towards the increased susceptibility of youth to concussion. Previous research efforts have considered the biomechanics of concussion for adult populations, but these known age-related differences highlight the necessity of quantifying the risk of concussion for a youth population. This study adapted the previously developed Generalized Acceleration Model for Brian Injury Threshold (GAMBIT) that combines linear and rotational head acceleration to model the risk of concussion for a youth population with the Generalized Acceleration Model for Concussion in Youth (GAM-CY).

Utilizing Whole Genomes To Identify, Correct, and Characterize Potential Virulence Protein Families.

spp. are Gram-negative, anaerobic, opportunistic pathogens involved in multiple diseases, including a link between the oral pathogen and the progression and severity of colorectal cancer. The identification and characterization of virulence factors in the genus has been greatly hindered by a lack of properly assembled and annotated genomes.

Analysis of brain subnetworks within the context of their whole-brain networks.

Analyzing the structure and function of the brain from a network perspective has increased considerably over the past two decades, with regional subnetwork analyses becoming prominent in the recent literature. However, despite the fact that the brain, as a complex system of interacting subsystems (i.e.

Chemical Modification of Alginate for Controlled Oral Drug Delivery.

Here, we report two methods that chemically modify alginate to achieve neutral-basic pH sensitivity of the resultant hydrogel. The first method involves direct amide bond formation between alginate and 4-(2-aminoethyl)benzoic acid. The second method that arose out of the desire to achieve better control of the degradation rate of the alginate hydrogel involves reductive amination of oxidized alginate.

Effects of exoskeleton design and precision requirements on physical demands and quality in a simulated overhead drilling task.

We compared three passive exoskeleton designs in a mock drilling task under three precision requirements levels, defined by required hole sizes, in terms of physical demands (perceived exertion and muscular activation) and quality. The investigated designs were: 1) an upper-body exoskeleton mainly supporting the shoulder; and both 2) full-body, and 3) upper-body exoskeletons, each with connected supernumerary arms. At a fixed pace, participants (n = 12) repeated "drilling" two same-sized holes for 2 min.

The feasibility of using dielectrophoresis for isolation of glioblastoma subpopulations with increased stemness.

Cancer stem cells (CSCs) are aggressive subpopulations with increased stem-like properties. CSCs are usually resistant to most standard therapies and are responsible for tumor repropagation. Similar to normal stem cells, isolation of CSCs is challenging due to the lack of reliable markers.

Assessing drug response in engineered brain microenvironments.

Tissue engineered systems are important models for the testing and discovery of therapeutics against a number of diseases. The use of these models in vitro can expand both our understanding of the mechanisms behind disease and allow for higher throughput and personalized modeling of therapeutic response. Over the past decade there has been an explosion of models of neurological disorders that can be used in vitro to study new therapies against devastating neurodegenerative, neurodevelopmental, and neuro-oncological disease.

Development of Zinc Chelating Resin Polymer Beads for the Removal of Cell-Free Hemoglobin.

Red blood cell (RBC) hemolysis is one of the most common storage lesions in packed RBCs (pRBC). Older units of pRBCs, especially those > 21 days old, have increasing levels of hemolysis leading to increased oxidative stress and premature platelet activation. This effect can mostly be attributed to the increase of cell-free hemoglobin (Hb).

3D bioprinting for high-throughput screening: Drug screening, disease modeling, and precision medicine applications.

High-throughput technologies have become essential in many fields of pharmaceutical and biological development and production. Such technologies were initially developed with compatibility with liquid handling-based cell culture techniques to produce large-scale 2D cell culture experiments for the compound analysis of candidate drug compounds. Over the past two decades, tools for creating 3D cell cultures, organoids, and other 3D models, such as cell supportive biomaterials and 3D bioprinting, have rapidly advanced.

In Situ Bioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds.

The early treatment and rapid closure of acute or chronic wounds is essential for normal healing and prevention of hypertrophic scarring. The use of split thickness autografts is often limited by the availability of a suitable area of healthy donor skin to harvest. Cellular and non-cellular biological skin-equivalents are commonly used as an alternative treatment option for these patients, however these treatments usually involve multiple surgical procedures and associated with high costs of production and repeated wound treatment.

Influences of different exoskeleton designs and tool mass on physical demands and performance in a simulated overhead drilling task.

We compared different passive exoskeletal designs in terms of physical demands (maximum acceptable frequency = MAF, perceived discomfort, and muscular loading) and quality in a simulated overhead drilling task, and the moderating influence of tool mass (∼2 and ∼5 kg). Three distinct designs were used: full-body and upper-body exoskeletons with attached mechanical arms; and an upper-body exoskeleton providing primarily shoulder support. Participants (n = 16, gender-balanced) simulated drilling for 15 min to determine their MAF, then maintained this pace for three additional minutes while the remaining outcome measures were obtained.

A multi-site metastasis-on-a-chip microphysiological system for assessing metastatic preference of cancer cells.

Metastatic disease remains one of the primary reasons for cancer-related deaths, yet the majority of in vitro cancer models focus on the primary tumor sites. Here, we describe a metastasis-on-a-chip device that houses multiple bioengineered three-dimensional (3D) organoids, established by a 3D photopatterning technique employing extracellular matrix-derived hydrogel biomaterials. Specifically, cancer cells begin in colorectal cancer (CRC) organoid, which resides in a single microfluidic chamber connected to multiple downstream chambers in which liver, lung, and endothelial constructs are housed.

Appendiceal Cancer Patient-Specific Tumor Organoid Model for Predicting Chemotherapy Efficacy Prior to Initiation of Treatment: A Feasibility Study.

Introduction: We have hypothesized that biofabrication of appendiceal tumor organoids allows for a more personalized clinical approach and facilitates research in a rare disease.

Methods: Appendiceal cancer specimens obtained during cytoreduction with hyperthermic intraperitoneal chemotherapy procedures (CRS/HIPEC) were dissociated and incorporated into an extracellular matrix-based hydrogel system as three-dimensional (3D), patient-specific tumor organoids. Cells were not sorted, preserving tumor heterogeneity, including stroma and immune cell components.