• Tissue-Engineered ECM Scaffolds for Modeling Digestive System Tumors
  • Leila Rezakhani,1,* Zahra Siefi,2
    1. Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
    2. Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran


  • Introduction: The extracellular matrix (ECM) is crucial in tumor biology, serving not just as a physical framework but also as a vital regulator of important cancer-related processes, such as invasion, metastasis, angiogenesis, immune evasion, and resistance to therapy. In breast cancer, the remodeling of the ECM leads to increased stiffness, disordered architecture, and modified biochemical signaling, all of which promote malignant progression and are associated with unfavorable clinical outcomes. Traditional 2D in vitro models are inadequate in mimicking these intricate microenvironmental factors, which limits their practical applicability. Conversely, 3D culture systems—particularly those that use decellularized ECM—provide a more physiologically relevant environment for studying tumor behavior, interactions between cells and the ECM, and responses to therapies in a manner that is more specific to patients and clinically relevant.
  • Methods: A search for studies from 2013 to 2025 was conducted in databases like PubMed, Scopus, and Web of Science, using targeted keywords related to decellularized extracellular matrix and tumor modeling. Articles were selected based on their relevance and quality to enhance the understanding of this emerging field.
  • Results: In colorectal cancer models, scaffolds based on a 3D ECM provide a more accurate representation of in vivo conditions than traditional 2D cultures. These models exhibited improved metastatic behavior, angiogenesis, and increased expression of epithelial-mesenchymal transition (EMT) markers—specifically, heightened levels of vimentin and diminished levels of E-cadherin—reflecting patient tumor characteristics closely. Notably, the scaffolds demonstrated greater resistance to 5-fluorouracil (5-FU), which corresponds with clinical evidence of chemoresistance. The use of decellularized matrices preserved the original ECM signals, enhancing tumor cell survival and invasiveness. Additionally, co-culturing with stromal and immune cells enriched the complexity of tumor-microenvironment interactions, providing a more authentic setting for assessing therapeutic effects and drug testing. These results highlight the potential of 3D models in advancing colorectal cancer research.
  • Conclusion: Decellularized ECM-based models provide a compelling platform for modeling patient-specific tumors by maintaining the native biochemical and structural characteristics of the tissue microenvironment. Nonetheless, their implementation encounters various challenges, such as the limited availability of human tissues and the variability in ECM composition. When sourced from animals, interspecies variations may undermine their translational significance. Additionally, ethical and regulatory considerations require careful sourcing and validation processes. Despite these challenges, decellularized ECM facilitates cell attachment, growth, and preservation of cellular phenotype. The addition of stromal fibroblasts, endothelial cells, and immune system components greatly improves the physiological relevance of these models. Overall, ECM-based platforms hold substantial potential for enhancing preclinical drug testing and personalized cancer treatment strategies.
  • Keywords: Decellularized tissues, Digestive system, Extracellular matrix, Cancer