Repurposing amniotic membrane as a native scaffold for cancer cell invasion studies

Modeling cancer cell invasion requires physiologically relevant systems, yet traditional 2D/3D assays and animal models fail to capture the biochemical and mechanical complexity of the human extracellular matrix (ECM). The human amniotic membrane (AM) is a clinically approved, abundant, and immunologically privileged tissue with a rich ECM composition and favorable mechanical properties. Despite its extensive use in regenerative medicine, its potential as a cancer invasion scaffold remains underexplored. We propose repurposing decellularized AM (dAM) as a human-derived ECM platform to study tumor invasion. dAM retains structural proteins, growth factor reservoirs, and stiffness gradients that influence epithelial-to-mesenchymal transition (EMT) and invasion pathways. Compared with conventional matrices, it offers improved biochemical fidelity and compatibility with patient-derived organoids. Key challenges, including donor variability, decellularization optimization, and reproducibility, are also addressed. dAM provides a non-invasive, scalable, and physiologically relevant tool for cancer invasion assays, drug screening, and patient-specific models. Its integration into oncology research may enhance translational relevance and accelerate personalized medicine.