Engineering a Lung‐Derived Extracellular Matrix‐GelMA Hydrogel to Elucidate Alterations in Lung Tumor‐Stroma‐On‐Chip
Makaleler > Tam Makale · 2026
Yazarlar: Aysel Saskara, Yagmur Arslan, Özlem YEŞİL ÇELİKTAŞ
Macromolecular Materials and Engineering, Uluslararası, Wos, 2026, cilt 311
DOI: 10.1002/mame.70274
Özet
ABSTRACT 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.