Development of an Injectable Hydrogel for Histotripsy Ablation Toward Future Glioblastoma Therapy Applications.

Glioblastoma (GBM) is the most common and malignant type of primary brain tumor. Even after surgery and chemoradiotherapy, residual GBM cells can infiltrate the healthy brain parenchyma to form secondary tumors. To mitigate GBM recurrence, we recently developed an injectable hydrogel that can be crosslinked in the resection cavity to attract, collect, and ablate residual GBM cells.

Fusobacterium nucleatum infection modulates the transcriptome and epigenome of HCT116 colorectal cancer cells in an oxygen-dependent manner.

Fusobacterium nucleatum, a gram-negative oral bacterium, has been consistently validated as a strong contributor to the progression of several types of cancer, including colorectal (CRC) and pancreatic cancer. While previous in vitro studies have shown that intracellular F. nucleatum enhances malignant phenotypes such as cell migration, the dependence of this regulation on features of the tumor microenvironment (TME) such as oxygen levels are wholly uncharacterized.

Electro-antibacterial therapy (EAT) to enhance intracellular bacteria clearance in pancreatic cancer cells.

Intratumoral bacteria have been implicated in driving tumor progression, yet effective treatments to modulate the tumor microbiome remain limited. In this study, we investigate the use of electroporation in combination with metronidazole to enhance the clearance of intracellular Fusobacterium nucleatum within pancreatic cancer cells. We explore various parameters, including electric field strength, pulse width, and pulse number to assess the permeability of pancreatic cancer cells infected with F.

Editorial: 'Engineering the Tumor Immune Microenvironment' Special Issue.

Cancer immunotherapies, while promising and occasionally even curative, encounter numerous hurdles within the tumor microenvironment that hinder their efficacy [...

High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas.

Background: Irreversible electroporation (IRE) has been previously investigated in preclinical trials as a treatment for intracranial malignancies. Here, we investigate next generation high-frequency irreversible electroporation (H-FIRE), as both a monotherapy and a combinatorial therapy, for the treatment of malignant gliomas.

Methods: Hydrogel tissue scaffolds and numerical modeling were used to inform H-FIRE pulsing parameters for our orthotopic tumor-bearing glioma model.

Development of a Synthetic, Injectable Hydrogel to Capture Residual Glioblastoma and Glioblastoma Stem-Like Cells with CXCL12-Mediated Chemotaxis.

Glioblastoma (GBM), characterized by high infiltrative capacity, is the most common and deadly type of primary brain tumor in adults. GBM cells, including therapy-resistant glioblastoma stem-like cells (GSCs), invade the healthy brain parenchyma to form secondary tumors even after patients undergo surgical resection and chemoradiotherapy. New techniques are therefore urgently needed to eradicate these residual tumor cells.

induces proliferation and migration in pancreatic cancer cells through host autocrine and paracrine signaling.

The tumor microbiome is increasingly implicated in cancer progression and resistance to chemotherapy. In pancreatic ductal adenocarcinoma (PDAC), high intratumoral loads of correlate with shorter survival in patients. Here, we investigated the potential mechanisms underlying this association.

High-Frequency Irreversible Electroporation (H-FIRE) Induced Blood-Brain Barrier Disruption Is Mediated by Cytoskeletal Remodeling and Changes in Tight Junction Protein Regulation.

Glioblastoma is the deadliest malignant brain tumor. Its location behind the blood-brain barrier (BBB) presents a therapeutic challenge by preventing effective delivery of most chemotherapeutics. H-FIRE is a novel tumor ablation method that transiently disrupts the BBB through currently unknown mechanisms.

Characterization and structure-property relationships of an injectable thiol-Michael addition hydrogel toward compatibility with glioblastoma therapy.

Glioblastoma multiforme (GBM) is an aggressive primary brain cancer and although patients undergo surgery and chemoradiotherapy, residual cancer cells still migrate to healthy brain tissue and lead to tumor relapse after treatment. New therapeutic strategies are therefore urgently needed to better mitigate this tumor recurrence. To address this need, we envision after surgical removal of the tumor, implantable biomaterials in the resection cavity can treat or collect residual GBM cells for their subsequent eradication.

Smooth Muscle Organization and Nerves in the Rat Vagina: A First Look Using Tissue Clearing and Immunolabeling.

Smooth muscle fibers within the vagina, as well as the nerve fibers that contribute to their control mechanisms, are important for the maintenance and alteration of vaginal length and tone. Vaginal smooth muscle (VaSM) is typically described as being arranged into two distinct concentric layers: an inner circular muscular layer and an outer longitudinal muscular layer. However, the distribution of VaSM oriented in the longitudinal direction (LD) and circumferential direction (CD) has never been quantified.

Comparative Analysis of Colon Cancer-Derived Fusobacterium nucleatum Subspecies: Inflammation and Colon Tumorigenesis in Murine Models.

Fusobacteria are commonly associated with human colorectal cancer (CRC), but investigations are hampered by the absence of a stably colonized murine model. Further, Fusobacterium nucleatum subspecies isolated from human CRC have not been investigated. While F.

Electroresponsive Hydrogels for Therapeutic Applications in the Brain.

Electroresponsive hydrogels possess a conducting material component and respond to electric stimulation through reversible absorption and expulsion of water. The high level of hydration, soft elastomeric compliance, biocompatibility, and enhanced electrochemical properties render these hydrogels suitable for implantation in the brain to enhance the transmission of neural electric signals and ion transport. This review provides an overview of critical electroresponsive hydrogel properties for augmenting electric stimulation in the brain.

Generation of Tumor-activated T cells Using Electroporation.

Expansion of cytotoxic T lymphocytes (CTLs) is a crucial step in almost all cancer immunotherapeutic methods. Current techniques for expansion of tumor-reactive CTLs present major limitations. This study introduces a novel method to effectively produce and expand tumor-activated CTLs using high-voltage pulsed electric fields.

A thermodynamic scaling law for electrically perturbed lipid membranes: Validation with steepest entropy ascent framework.

Experimental evidence has demonstrated the ability of transient pulses of electric fields to alter mammalian cell behavior. Strategies with these pulsed electric fields (PEFs) have been developed for clinical applications in cancer therapeutics, in-vivo decellularization, and tissue regeneration. Successful implementation of these strategies involve understanding how PEFs impact the cellular structures and, hence, cell behavior.

Web Conferencing Facilitation Within Problem-Based Learning Biomedical Engineering Courses.

Problem-based learning (PBL) has been effectively used within BME education, though there are several challenges in its implementation within courses with larger enrollments. Furthermore, the sudden transition to online learning from the COVID-19 pandemic introduced additional challenges in creating a similar PBL experience in an online environment. Online constrained PBL was implemented through asynchronous modules and synchronous web conferencing with rotating facilitators.

Harnessing Tissue Engineering Tools to Interrogate Host-Microbiota Crosstalk in Cancer.

Recent studies have begun to highlight the diverse and tumor-specific microbiomes across multiple cancer types. We believe this work raises the important question of whether the classical "Hallmarks of Cancer" should be expanded to include tumor microbiomes. To answer this question, the causal relationships and co-evolution of these microbiotic tumor ecosystems must be better understood.

Electro-chemo-mechanical model to investigate multi-pulse electric-field-driven integrin clustering.

The effect of pulsed electric fields (PEFs) on transmembrane proteins is not fully understood; how do chemo-mechanical cues in the microenvironment mediate the electric field sensing by these proteins? To answer this key gap in knowledge, we have developed a kinetic Monte Carlo statistical model of the integrin proteins that integrates three components of the morphogenetic field (i.e., chemical, mechanical, and electrical cues).

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.

Effects of culture condition on epigenomic profiles of brain tumor cells.

Personalized cancer medicine offers the promise of more effective treatments that are tailored to an individual's own dynamic cancer phenotype. Meanwhile, tissue-engineering approaches to modeling tumors may complement these advances by providing a powerful new approach to understanding the adaptation dynamics occurring during treatment. However, in both of these areas new tools will be required to gain a full picture of the genetic and epigenetic regulators of phenotype dynamics occurring in the small populations of cells that drive resistance.

Temporal Characterization of Blood-Brain Barrier Disruption with High-Frequency Electroporation.

Treatment of intracranial disorders suffers from the inability to accumulate therapeutic drug concentrations due to protection from the blood-brain barrier (BBB). Electroporation-based therapies have demonstrated the capability of permeating the BBB, but knowledge of the longevity of BBB disruption (BBBD) is limited. In this study, we quantify the temporal, high-frequency electroporation (HFE)-mediated BBBD in an in vivo healthy rat brain model.

Understanding the role of calcium-mediated cell death in high-frequency irreversible electroporation.

High-frequency irreversible electroporation (H-FIRE) is an emerging electroporation-based therapy used to ablate cancerous tissue. Treatment consists of delivering short, bipolar pulses (1-10μs) in a series of 80-100 bursts (1 burst/s, 100μs on-time). Reducing pulse duration leads to reduced treatment volumes compared to traditional IRE, therefore larger voltages must be applied to generate ablations comparable in size.

Characterization of Ablation Thresholds for 3D-Cultured Patient-Derived Glioma Stem Cells in Response to High-Frequency Irreversible Electroporation.

High-frequency irreversible electroporation (H-FIRE) is a technique that uses pulsed electric fields that have been shown to ablate malignant cells. In order to evaluate the clinical potential of H-FIRE to treat glioblastoma (GBM), a primary brain tumor, we have studied the effects of high-frequency waveforms on therapy-resistant glioma stem-like cell (GSC) populations. We demonstrate that patient-derived GSCs are more susceptible to H-FIRE damage than primary normal astrocytes.

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.

High-frequency irreversible electroporation is an effective tumor ablation strategy that induces immunologic cell death and promotes systemic anti-tumor immunity.

Background: Despite promising treatments for breast cancer, mortality rates remain high and treatments for metastatic disease are limited. High-frequency irreversible electroporation (H-FIRE) is a novel tumor ablation technique that utilizes high-frequency bipolar electric pulses to destabilize cancer cell membranes and induce cell death. However, there is currently a paucity of data pertaining to immune system activation following H-FIRE and other electroporation based tumor ablation techniques.