Exploring Mechanical Features of 3D Head and Neck Cancer ModelsEvangelista, Scocozza, Conti
et alJ Funct Biomater (2025) 16 (3)
Abstract: Head and neck squamous cell carcinoma (HNSCC) presents significant challenges in oncology due to its complex biology and poor prognosis. Traditional two-dimensional (2D) cell culture models cannot replicate the intricate tumor microenvironment, limiting their usefulness in studying disease mechanisms and testing therapies. In contrast, three-dimensional (3D) in vitro models provide more realistic platforms that better mimic the architecture, mechanical features, and cellular interactions of HNSCC. This review explores the mechanical properties of 3D in vitro models developed for HNSCC research. It highlights key 3D culture techniques, such as spheroids, organoids, and bioprinted tissues, emphasizing their ability to simulate critical tumor characteristics like hypoxia, drug resistance, and metastasis. Particular attention is given to stiffness, elasticity, and dynamic behavior, highlighting how these models emulate native tumor tissues. By enhancing the physiological relevance of in vitro studies, 3D models offer significant potential to revolutionize HNSCC research and facilitate the development of effective, personalized therapeutic strategies. This review bridges the gap between preclinical and clinical applications by summarizing the mechanical properties of 3D models and providing guidance for developing systems that replicate both biological and mechanical characteristics of tumor tissues, advancing innovation in cancer research and therapy.
Pathway-like Activation of 3D Neuronal Constructs with an Optical InterfaceOmidi, Berdichevsky
Biosensors (Basel) (2025) 15 (3)
Abstract: Three-dimensional neuronal organoids, spheroids, and tissue mimics are increasingly used to model cognitive processes in vitro. These 3D constructs are also used to model the effects of neurological and psychiatric disorders and to perform computational tasks. The brain's complex network of neurons is activated via feedforward sensory pathways. Therefore, an interface to 3D constructs that models sensory pathway-like inputs is desirable. In this work, an optical interface for 3D neuronal constructs was developed. Dendrites and axons extended by cortical neurons within the 3D constructs were guided into microchannel-confined bundles. These neurite bundles were then optogenetically stimulated, and evoked responses were evaluated by calcium imaging. Optical stimulation was designed to deliver distinct input patterns to the network in the 3D construct, mimicking sensory pathway inputs to cortical areas in the intact brain. Responses of the network to the stimulation possessed features of neuronal population code, including separability by input pattern and mixed selectivity of individual neurons. This work represents the first demonstration of a pathway-like activation of networks in 3D constructs. Another innovation of this work is the development of an all-optical interface to 3D neuronal constructs, which does not require the use of expensive microelectrode arrays. This interface may enable the use of 3D neuronal constructs for investigations into cortical information processing. It may also enable studies into the effects of neurodegenerative or psychiatric disorders on cortical computation.
Non-Invasive and Long-Term Electrophysiological Monitoring Sensors for Cerebral Organoids DifferentiationJin, Guo, Li
et alBiosensors (Basel) (2025) 15 (3)
Abstract: Cerebral organoids derived from human induced pluripotent stem cells (iPSCs) have emerged as powerful in vitro models for studying human brain development and neurological disorders. Understanding the electrophysiological properties of these organoids is crucial for evaluating their functional maturity and potential applications. However, the differentiation and maturation of stem cells into cerebral organoids is a long, slow, and error-prone process. Hence, it is vitally crucial to establish a non-invasive method of monitoring the process over a long period of time. In this study, a planar microelectrode array (MEA) with platinum (Pt) black electroplating is designed to monitor the electrophysiological activities and pharmacological responses of cerebral organoids using an external neural signal acquisition system interfaced with the MEA. The planar MEA with Pt black electroplating has a significantly reduced electrode impedance and exhibits a robust capability for the real-time detection of spontaneous neural activities, including extracellular spikes and local field potentials. Distinct electrophysiological signal strengths in cerebral organoids were observed at early and late developmental stages. Further pharmacological stimulations showed that 30 mM KCl would induce a marked increase in spike rate, indicating an enhancement of neuronal depolarization and an elevation of network excitability. This robust response to KCl stimulation in mature networks serves as a reliable indicator of neural maturity in cerebral organoids and underscores the platform's potential for drug screening applications. This work highlights the integration of MEA technology with cerebral organoids, offering a powerful platform for real-time electrophysiological monitoring. It provides new insights into the functional maturation of neural networks and establishes a reliable system for drug screening and disease modeling, facilitating future research into human brain physiology and pathology.
Colorectal Organoids: Models, Imaging, Omics, Therapy, Immunology, and EthicsTaglieri, Di Gregorio, Matis
et alCells (2025) 14 (6)
Abstract: Colorectal epithelium was the first long-term 3D organoid culture established in vitro. Identification of the key components essential for the long-term survival of the stem cell niche allowed an indefinite propagation of these cultures and the modulation of their differentiation into various lineages of mature intestinal epithelial cells. While these methods were eventually adapted to establish organoids from different organs, colorectal organoids remain a pioneering model for the development of new applications in health and disease. Several basic and applicative aspects of organoid culture, modeling, monitoring and testing are analyzed in this review. We also tackle the ethical problems of biobanking and distribution of these precious research tools, frequently confined in the laboratory of origin or condemned to destruction at the end of the project.
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