Ozlem Yesil-Celiktas

Lung cancer progression is regulated by dynamic alterations in the extracellular matrix (ECM), yet these changes remain insufficiently captured in conventional in vitro models. Here, we present a biomimetic lung tumor‐stroma‐on‐chip integrating a decellularized lung‐derived ECM (dlECM) with gelatin methacrylate (GelMA) hydrogel to recapitulate tissue‐specific microenvironmental dynamics. The decellularization protocol was optimized to achieve approximately 98%–99% DNA removal, while maintaining the integrity of key ECM components including ∼70% collagen, ∼62% elastin, and near‐complete retention of sGAGs, ensuring biochemical fidelity. The hybrid GelMA‐dlECM hydrogel was engineered to support a multicellular architecture, where lung carcinoma cells formed a central tumor focus, surrounded by fibroblasts and overlaid with epithelial cells, emulating the lung tumor microenvironment. Mechanical characterization revealed an increase in matrix stiffness in the tumor model (154.7 Pa) compared to the healthy one (108.29 Pa), accompanied by elevated collagen and elastin deposition, indicating cancer‐associated matrix remodeling. Consistent with these findings, MMP‐2 and MMP‐9 levels were markedly upregulated at early time points, reflecting active ECM degradation and remodeling processes. Collectively, this platform demonstrates how the interplay between biochemical composition and mechanical properties governs tumor evolution, providing a physiologically relevant model for investigating ECM‐driven mechanisms in lung cancer and for future therapeutic screening applications.

Engineering physiologically relevant vascular models remains a challenge in cancer biology and tissue engineering. Here, we present a microfluidic wet‐spinning methodology for the biofabrication of cell‐laden alginate‐gelatin methacryloyl (GelMA) hydrogel‐based vessel‐like structures with controlled geometry and perfusable architecture. Using a sacrificial gelatin core within a core–shell microfluidic device, tubular scaffolds were produced in a single continuous step under mild, cell‐compatible conditions. The alginate‐GelMA shell is fine‐tuned and loaded with human umbilical vein endothelial cells (HUVEC), yielding an endothelialized‐like, perfusable construct at the small‐vein scale (∼0.6–0.7 mm lumen diameter). As a proof‐of‐concept use case, the biofabricated vessel‐like structure was integrated into the breast cancer‐on‐a‐chip (BCoC) platform to showcase its feasibility in a 3D vascularized‐like tumor model for interrogating cancer cell propagation. Breast cancer spheroids were positioned in the surrounding GelMA matrix (perivascular‐like compartment), and THP‐1 monocytes were circulated through the perfusion platform. Cancer cell dissemination, quantified as circulating tumor cells (CTCs), was modulated by the immune microenvironment: interleukin‐4 (IL‐4, anti‐inflammatory‐like) conditions promoted peak CTC release, whereas lipopolysaccharide (LPS, pro‐inflammatory‐like) stimulation suppressed this dissemination. Our model integrates the vascular, tumor, and immune compartments within a single construct, providing a versatile platform for investigations of breast cancer dissemination and tumor‐immune crosstalk.

The Impact of the Exposome on Epithelial Barriers: New Approach Methodologies for Translational Research - Thoracic Research and Practice

Under the influence of environmental pollution, chronic non‐communicable diseases have increased. The epithelial lining of the airway forms the initial barrier; however, upon exposure, nanoplastics (NPs) may cross this interface and enter systemic circulation. This study aims to elucidate the effects of polypropylene nanoplastics (PP NPs) on the epithelial barrier and the interactions with serum proteins. PP beads were chemically degraded, characterized, and administered to the epithelial barrier‐on‐chip at a dose of 250 μg/mL, followed by continuous perfusion for 3 days. Their colloidal and biological behavior was investigated in cell culture medium supplemented with 10% fetal bovine serum. To explore clinical relevance, the interaction of PP NPs with human serum albumin was analyzed using molecular dynamics simulations, supported by protein profiling of plasma samples from healthy male and female individuals to understand gender‐related differences. PP NPs with an average size of 305 nm were exposed to the epithelial barrier‐on‐chip leading to a decrease in cell viability via apoptotic cell death and transepithelial electrical resistance (TEER) value from ~2600 to 2200 Ω·cm ² with altered ZO‐1 and ACE2 expression, as well as an increased proinflammatory response and intracellular reactive oxygen species (ROS) levels. [Correction added on 15 April 2026, after first online publication: The word “suppressed” has been deleted from the ] The size of NPs increased to 364 nm after incubation with cell culture medium, indicating protein corona formation. The simulation revealed a biphasic adsorption pattern. The major differences in blood plasma of male and female donors were observed in the protein bands around 130 and 180 kDa. By integrating experimental and computational approaches, this study advances our understanding of how inhaled NPs may interact with blood proteins upon systemic exposure, with potential implications for human health risk assessment.

Dust exposure affects an estimated 330 million people worldwide and can penetrate deep into the respiratory tract, disrupting epithelial and endothelial barriers. However, current in vitro models do not recapitulate the perfusable airway-vascular interface required to investigate dust-induced barrier alterations. Bioinspired scaffolds from decellularized plants hold strong potential as new approach methodologies (NAMs), considering the need for physiologically relevant in vitro models with vascular networks. Herein, we developed a decellularized plant-based air–liquid interface (ALI)-on-a-chip to study inorganic dust aerosol exposure in human airway epithelial barrier. The decellularization method achieved ≥ 99% DNA removal and a hydrophilic interface, while preserving vascular network and cellulose-rich extracellular matrix. Subsequently, human umbilical vein endothelial cells and bronchial epithelial cells were seeded to the decellularized scaffold, positioned on a PDMS-based platform to reconstruct a perfusable ALI-on-a-chip. Nanoscale dust particles were administered to the epithelium. The dust particles resulted in a significant decrease in barrier integrity, where the TEER value of the epithelial barrier decreased from ~ 126.42 to ~ 56.11Ω*cm², with altered cell viabilities, and significant increases in pro-inflammatory cytokines such as TNF-α and IL-6. Our study reports the effects of inhaled dust aerosols on pulmonary barriers, along with offering a plant-based, biocompatible, and tissue-emulating air–liquid interface on-a-chip model. The developed model offers a versatile platform for studying toxicity of diverse particles and a preclinical evaluation of respiratory therapeutics.

Hydrogel Formulations to Investigate Lung Cancer Mechanism - Thoracic Research and Practice

A NAMs-Based Microphysiological System for Metastasis and Mechanobiology Studies - Thoracic Research and Practice

Occupational and Environmental Exposures: Trends in Publications, Diseases, and Experimental Models - Thoracic Research and Practice