Semiconducting polymer nanoparticles for photothermal ablation of colorectal cancer organoids.

Colorectal cancer (CRC) treatment is currently hindered by micrometastatic relapse that cannot be removed completely during surgery and is often chemotherapy resistant. Targeted theranostic nanoparticles (NPs) that can produce heat for ablation and enable tumor visualization via their fluorescence offer advantages for detection and treatment of disseminated small nodules. A major hurdle in clinical translation of nanoparticles is their interaction with the 3D tumor microenvironment.

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.

Personalized Identification of Optimal HIPEC Perfusion Protocol in Patient-Derived Tumor Organoid Platform.

Background: Chemotherapy dosing duration and perfusion temperature vary significantly in HIPEC protocols. This study investigates patient-derived tumor organoids as a platform to identify the most efficacious perfusion protocol in a personalized approach.

Patients And Methods: Peritoneal tumor tissue from 15 appendiceal and 8 colon cancer patients who underwent CRS/HIPEC were used for personalized organoid development.

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.

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.

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.

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 Colorectal Cancer 3D Micro-tumor Construct Platform From Cell Lines and Patient Tumor Biospecimens for Standard-of-Care and Experimental Drug Screening.

Colorectal cancer is subject to a high rate of mutations, with late stage tumors often containing many mutations. These tumors are difficult to treat, and even with the recently implemented methods of personalized medicine at modern hospitals aiming to narrow treatments, a gap still exists. Proper modeling of these tumors may help to recommend optimal treatments for individual patients, preferably utilizing a model that maintains proper signaling in respect to the derived parent tissue.

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.

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.

CD38 Inhibits Prostate Cancer Metabolism and Proliferation by Reducing Cellular NAD Pools.

Tumor cells require increased rates of cell metabolism to generate the macromolecules necessary to sustain proliferation. They rely heavily on NAD as a cofactor for multiple metabolic enzymes in anabolic and catabolic reactions. NAD also serves as a substrate for PARPs, sirtuins, and cyclic ADP-ribose synthases.

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.

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.

Applications of Bioengineered 3D Tissue and Tumor Organoids in Drug Development and Precision Medicine: Current and Future.

Over the past decade, advances in biomedical and tissue engineering technologies, such as cell culture techniques, biomaterials, and biofabrication, have driven increasingly widespread use of three-dimensional (3D) cell culture platforms and, subsequently, the use of organoids in a variety of research endeavors. Given the 3D nature of these organoid systems, and the frequent inclusion of extracellular matrix components, these constructs typically have more physiologically accurate cell-cell and cell-matrix interactions than traditional 2D cell cultures. As a result, 3D organoids can serve as better model systems than their 2D counterparts.

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.

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.