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The NLRP3 inflammasome plays a crucial role in the inflammatory response, reacting to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). This response is essential for combating infections and restoring tissue homeostasis. However, chronic activation can lead to detrimental effects, particularly in neuropsychiatric and neurodegenerative diseases. Our study seeks to provide a method to effectively measure the NLRP3 inflammasome's activation within cerebral organoids (COs), providing insights into the underlying pathophysiology of these conditions and enabling future studies to investigate the development of targeted therapies. [ABSTRACT FROM AUTHOR]

Shape-controlled 3D tissues resemble natural living tissues in human and animal bodies and are essential materials for developing and improving technologies in regenerative medicine, drug discovery, and biological robotics. In previous studies, shape-controlled 3D tissues were fabricated using scaffold structures or 3D bioprinting techniques. However, controlling the shape of 3D tissues without leaving non-natural materials inside the 3D tissue and efficiently fabricating them remains challenging. In this paper, we propose a novel method for fabricating shape-controlled 3D tissues free of non-natural materials using a flexible high-porosity porous structure (HPPS). The HPPS consisted of a micromesh with pore sizes of 14.87 ± 1.83 μm, lattice widths of 2.24 ± 0.10 μm, thicknesses of 9.96 ± 0.92 μm, porosity of 69.06 ± 3.30%, and an I-shaped microchamber of depth 555.26 ± 11.17 μm. U-87 human glioma cells were cultured in an I-shaped HPPS microchamber for 48 h. After cultivation, the 3D tissue was released within a few seconds while maintaining its I-shape. Specific chemicals, such as proteolytic enzymes, were not used. Moreover, the viability of the released cells composed of shape-controlled 3D tissues free of non-natural materials was above 90%. Therefore, the proposed fabrication method is recommended for shape-controlled 3D tissues free of non-natural materials without applying significant stresses to the cells. [ABSTRACT FROM AUTHOR]

Inflammation plays a pivotal role in the development and progression of inflammatory bowel disease (IBD), by contributing to tissue damage and exacerbating the immune response. The investigation of serotonin receptor 2A (5-HT2A) ligands and transient receptor potential (TRP) channel ligands is of significant interest due to their potential to modulate key inflammatory pathways, mitigate the pathological effects of inflammation, and offer new avenues for therapeutic interventions in IBD. This study investigates the anti-inflammatory effects of 5-HT2A ligands, including psilocybin, 4-AcO-DMT, and ketanserin, in combination with TRP channel ligands, including capsaicin, curcumin, and eugenol, on the inflammatory response induced by tumor necrosis factor (TNF)-α and interferon (IFN)-γ in human 3D EpiIntestinal tissue. Enzyme-linked immunosorbent assay was used to assess the expression of pro-inflammatory markers TNF-α, IFN-γ, IL-6, IL-8, MCP-1, and GM-CSF. Our results show that psilocybin, 4-AcO-DMT, and eugenol significantly reduce TNF-α and IFN-γ levels, while capsaicin and curcumin decrease these markers to a lesser extent. Psilocybin effectively lowers IL-6 and IL-8 levels, but curcumin, capsaicin, and 4-AcO-DMT have limited effects on these markers. In addition, psilocybin can significantly decrease MCP-1 and GM-CSF levels. While ketanserin lowers IL-6 and GM-CSF levels, there are no effects seen on TNF-α, IFN-γ, IL-8, or MCP-1. Although synergistic effects between 5-HT2A and TRP channel ligands are minimal in this study, the results provide further evidence of the anti-inflammatory effects of psilocybin and eugenol. Further research is needed to understand the mechanisms of action and the feasibility of using these compounds as anti-inflammatory therapies for conditions like IBD. [ABSTRACT FROM AUTHOR]

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a new source of cardiac cells are expected to find use as tools in high-throughput screening for drug candidates and cardiotoxicity validation without the need for experimentation on animals. In recent years, it has been reported that drug screening using three-dimensional (3D) tissue is better than conventional 2D culture. Various methods have been developed for mass culture of hiPSC-CMs, and embryoid body (EB) formation is necessary in the majority of differentiation methods as this is reported to promote the differentiation of hiPSCs. However, these operations result in increased processing, cost and loss of hiPSCs. Here, we show alternative methods for differentiation to hiPSC-CMs from <100 μm hiPSC-clumps without EB formation and report on a 3D-tissue fabrication using hiPSC-CMs. The 3D cardiac tissue constructed by a layer-by-layer (LbL) cell coating technique (LbL-3D Heart) showed synchronous powerful beating. We conclude that this method enables cost-effective, reproducible and scalable hiPSC-CM production with high activity for tissue engineering, drug screening and regenerative medicine. [ABSTRACT FROM AUTHOR]

Abstract A challenge in developing effective treatments is the modeling of the human disease using in vitro and in vivo systems. Animal models have played a critical role in the understanding of disease pathophysiology, target validation, and evaluation of novel therapeutic agents. However, as the success rate from entry into clinical testing to drug approval remains low, it is critical to have high quality and well-validated models reflective of the disease condition. Additional experimental models are being developed based on functional in vitro 3D tissue models such as organoids and 3D bioprinted tissues. Because these 3D tissue models mimic closer the architecture, cell composition and physiology of native tissues, they are now being used as screening platforms in drug discovery and development and for tissue transplant in regenerative medicine. Here we review the current state-of-art of in vitro and in vivo translational models for the development of therapies for rare diseases of the liver. Highlights • Targeting early steps of liver disease progression can lead to more successful therapeutic interventions. • Validated animal models reflective of human liver disease phenotypes increase predictability of drug toxicity and efficacy. • 3D liver tissue models are being developed as in vitro platforms for drug development and regenerative medicine. [ABSTRACT FROM AUTHOR]

The ability to accurately detect cardiotoxicity has become increasingly important in the development of new drugs. Since the advent of human pluripotent stem cell-derived cardiomyocytes, researchers have explored their use in creating an in vitro drug screening platform. Recently, there has been increasing interest in creating 3D microphysiological models of the heart as a tool to detect cardiotoxic compounds. By recapitulating the complex microenvironment that exists in the native heart, cardiac microphysiological systems have the potential to provide a more accurate pharmacological response compared to current standards in preclinical drug screening. This review aims to provide an overview on the progress made in creating advanced models of the human heart, including the significance and contributions of the various cellular and extracellular components to cardiac function. [ABSTRACT FROM AUTHOR]

Abstract: A hormone-responsive 3D human tissue-like culture system was developed in which human primary mammary epithelial cells (MECs) were co-cultured with two types of predominant mammary stromal cells on silk protein scaffolds. Silk porous scaffolds with incorporated extracellular matrix provided a compatible environment for epithelial structure morphogenesis and differentiation. The presence of stromal cells promoted MEC proliferation, induced both alveolar and ductal morphogenesis and enhanced casein expression. In contrast, only alveolar structures were observed in monocultures. The alveolar structures generated from the heterotypic cultures in vitro exhibited proper polarity similar to human breast tissue in vivo. Consistent with their phenotypic appearance, more functional differentiation of epithelial cells was also observed in the heterotypic cultures, where casein-α and -β mRNA expression were increased significantly. Additionally, this 3D multicellular culture model displayed an estrogen-responsive physiologically relevant response, evidenced by enhanced cell proliferation, aberrant morphology, changes in gene expression profile and few polarized lumen structures after estrogen treatment. This culture system offers an excellent opportunity to explore the role of cell–cell and cell–substrate interactions during mammary gland development, the consequences of hormone receptor activation on MEC behavior and morphogenesis, as well as their alteration during neoplastic transformation in human breast tissue. [Copyright &y& Elsevier]

Organ on chip (OOC) has emerged as a major technological breakthrough and distinct model system revolutionizing biomedical research and drug discovery by recapitulating the crucial structural and functional complexity of human organs in vitro. OOC are rapidly emerging as powerful tools for oncology research. Indeed, Cancer on chip (COC) can ideally reproduce certain key aspects of the tumor microenvironment (TME), such as biochemical gradients and niche factors, dynamic cell–cell and cell–matrix interactions, and complex tissue structures composed of tumor and stromal cells. Here, we review the state of the art in COC models with a focus on the microphysiological systems that host multicellular 3D tissue engineering models and can help elucidate the complex biology of TME and cancer growth and progression. Finally, some examples of microengineered tumor models integrated with multi-organ microdevices to study disease progression in different tissues will be presented. [ABSTRACT FROM AUTHOR]

The vascularization of three-dimensional (3D) tissue constructs is necessary for transporting nutrients and oxygen to the component cells. In this study, a vacuum forming method was applied to emboss a vascular pattern on an electrospun membrane so that guided vascular structures could develop within the construct. Two- or six-layer constructs of electrospun membranes seeded with endothelial cells and pericytes were stacked and subcutaneously implanted into mice. Blood vessel formation in the implanted constructs with six alternating layers of flat membranes and membranes embossed with a blood vessel pattern was observed after two weeks of implantation. The formation of blood vessels was observed along the embossed blood vessel pattern in the structure of the embossed membrane laminated at four weeks and eight weeks. Vascular endothelial growth factor (VEGF) and angiopoietin 1 (Ang-1) were highly expressed in the vascularized structures. Therefore, we demonstrated that a structure capable of producing a desired blood vessel shape with electrospun membranes embossed with a blood vessel pattern can be manufactured, and that a variety of structures can be manufactured using electrospun membranes in the tissue engineering era. [ABSTRACT FROM AUTHOR]