Understanding glioblastoma stromal barriers against NK cell attack using tri-culture 3D spheroid model.

Glioblastoma multiforme (GBM), a highly aggressive tumor type with a dismal survival rate, has a poor outcome which is at least partly attributed to the crosstalk between cancer cells and cells from the tumor microenvironment such as astrocytes and microglia. We aimed to decipher the effect of these cells on GBM progression and on cell-based therapies using 3D co-cultures. Co-culturing of glioblastoma cells with patient-derived astrocytes or microglia or both formed dense and heterogeneous spheroids.

Endotoxin contamination alters macrophage-cancer cell interaction and therapeutic efficacy in pre-clinical 3D in vitro models.

The rapid developments in biofabrication, in particular 3D bioprinting, in the recent years have facilitated the need for novel biomaterials that aim to replicate the target tissue in great detail. The presence of endotoxins in these biomaterials is often an overlooked problem. In pre-clinical 3D in vitro models, endotoxins can have significant influence on cell behavior and credibility of the model.

Microarchitectural mimicking of stroma-induced vasculature compression in pancreatic tumors using a 3D engineered model.

Fibrotic tumors, such as pancreatic ductal adenocarcinoma (PDAC), are characterized for high desmoplastic reaction, which results in high intra-tumoral solid stress leading to the compression of blood vessels. These microarchitectural alterations cause loss of blood flow and poor intra-tumoral delivery of therapeutics. Currently, there is a lack of relevant in vitro models capable of replicating these mechanical characteristics and to test anti-desmoplastic compounds.

Cancer immune therapy using engineered ‛tail-flipping' nanoliposomes targeting alternatively activated macrophages.

Alternatively-activated, M2-like tumor-associated macrophages (TAM) strongly contribute to tumor growth, invasiveness and metastasis. Technologies to disable the pro-tumorigenic function of these TAMs are of high interest to immunotherapy research. Here we show that by designing engineered nanoliposomes bio-mimicking peroxidated phospholipids that are recognised and internalised by scavenger receptors, TAMs can be targeted.

Mimicking tumor microenvironment by 3D bioprinting: 3D cancer modeling.

The tumor microenvironment (TME) typically comprises cancer cells, tumor vasculature, stromal components like fibroblasts, and host immune cells that assemble to support tumorigenesis. However, preexisting classic cancer models like 2D cell culture methods, 3D cancer spheroids, and tumor organoids seem to lack essential TME components. 3D bioprinting offers enormous advantages for developingtumor models by allowing user-controlled deposition of multiple biomaterials, cells, and biomolecules in a predefined architecture.

Impact of endotoxins on bioengineered tissues and models.

Endotoxins are commonly present in both naturally derived and synthetic biomaterials. This Forum highlights the consequences of endotoxin contamination in biomaterials on different engineered tissues, such as bone, skin, or cartilage, and discusses the potential effects on novel 3D immunocompetent pathophysiological models.

Novel 3D µtissues Mimicking the Fibrotic Stroma in Pancreatic Cancer to Study Cellular Interactions and Stroma-Modulating Therapeutics.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor type with low patient survival due to the low efficacy of current treatment options. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) create a dense fibrotic environment around the tumor cells, preventing therapies from reaching their target. Novel 3D in vitro models are needed that mimic this fibrotic barrier for the development of therapies in a biologically relevant environment.

Translating complexity and heterogeneity of pancreatic tumor: 3D in vitro to in vivo models.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive type of cancer with an overall survival rate of less than 7-8%, emphasizing the need for novel effective therapeutics against PDAC. However only a fraction of therapeutics which seemed promising in the laboratory environment will eventually reach the clinic. One of the main reasons behind this low success rate is the complex tumor microenvironment (TME) of PDAC, a highly fibrotic and dense stroma surrounding tumor cells, which supports tumor progression as well as increases the resistance against the treatment.

3D In Vitro Model (R)evolution: Unveiling Tumor-Stroma Interactions.

The complex microenvironment in which malignant tumor cells grow is crucial for cancer progression. The physical and biochemical characteristics of this niche are involved in controlling cancer cell differentiation, proliferation, invasion, and metastasis. It is therefore essential to understand how cancer cells interact and communicate with their surrounding tissue - the so-called tumor stroma - and how this interplay regulates disease progression.

Nanomedicine strategies to target coronavirus.

With the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, the middle east respiratory syndrome CoV (MERS-CoV) in 2012 and the recently discovered SARS-CoV-2 in December 2019, the 21st first century has so far faced the outbreak of three major coronaviruses (CoVs). In particular, SARS-CoV-2 spread rapidly over the globe affecting nearly 25.000.

3D Bioprinting: from Benches to Translational Applications.

Over the last decades, the fabrication of 3D tissues has become commonplace in tissue engineering and regenerative medicine. However, conventional 3D biofabrication techniques such as scaffolding, microengineering, and fiber and cell sheet engineering are limited in their capacity to fabricate complex tissue constructs with the required precision and controllability that is needed to replicate biologically relevant tissues. To this end, 3D bioprinting offers great versatility to fabricate biomimetic, volumetric tissues that are structurally and functionally relevant.

3D-Bioprinted Mini-Brain: A Glioblastoma Model to Study Cellular Interactions and Therapeutics.

Glioblastoma-associated macrophages (GAMs) play a crucial role in the progression and invasiveness of glioblastoma multiforme (GBM); however, the exact crosstalk between GAMs and glioblastoma cells is not fully understood. Furthermore, there is a lack of relevant in vitro models to mimic their interactions. Here, novel 3D-bioprinted mini-brains consisting of glioblastoma cells and macrophages are presented as tool to study the interactions between these two cell types and to test therapeutics that target this interaction.

Reprogramming tumor stroma using an endogenous lipid lipoxin A4 to treat pancreatic cancer.

Pancreatic stellate cells (PSCs) are the precursors of cancer-associated fibroblasts (CAFs), which potentiate pancreatic tumor growth and progression. In this study, we investigated whether Lipoxin A4 (LXA4), an endogenous bioactive lipid, can inhibit the differentiation of human PSCs (hPSCs) into CAF-like myofibroblasts and thereby hPSC-induced pro-tumorigenic effects. LXA4 significantly inhibited TGF-β-mediated differentiation of hPSCs by inhibiting pSmad2/3 signalling.

Embedded Multimaterial Extrusion Bioprinting.

Embedded extrusion bioprinting allows for the generation of complex structures that otherwise cannot be achieved with conventional layer-by-layer deposition from the bottom, by overcoming the limits imposed by gravitational force. By taking advantage of a hydrogel bath, serving as a sacrificial printing environment, it is feasible to extrude a bioink in freeform until the entire structure is deposited and crosslinked. The bioprinted structure can be subsequently released from the supporting hydrogel and used for further applications.

Extrusion Bioprinting of Shear-Thinning Gelatin Methacryloyl Bioinks.

Bioprinting is an emerging technique for the fabrication of 3D cell-laden constructs. However, the progress for generating a 3D complex physiological microenvironment has been hampered by a lack of advanced cell-responsive bioinks that enable bioprinting with high structural fidelity, particularly in the case of extrusion-based bioprinting. Herein, this paper reports a novel strategy to directly bioprint cell-laden gelatin methacryloyl (GelMA) constructs using bioinks of GelMA physical gels (GPGs) achieved through a simple cooling process.

Rapid Continuous Multimaterial Extrusion Bioprinting.

The development of a multimaterial extrusion bioprinting platform is reported. This platform is capable of depositing multiple coded bioinks in a continuous manner with fast and smooth switching among different reservoirs for rapid fabrication of complex constructs, through digitally controlled extrusion of bioinks from a single printhead consisting of bundled capillaries synergized with programmed movement of the motorized stage.