Ovarian cancer remains the deadliest of the gynecological cancers, where this arises from poor screening and imaging tools that can detect early disease. To demonstrate underlying differences in fiber morphology and density which are related to tissue stiffness, in a spectrum of normal and diseases, we use a combination of wavelength dependent Second Harmonic Generation (SHG) and optical scattering measurements. To gain insight into how these structural details affect resulting underlying cellular dynamics, we have used multiphoton excited fabrication to create SHG image-based orthogonal models from collagen/GelMA that represent both the collagen matrix morphology and stiffness (~2-8 kPa) of normal ovarian stroma and high grade serous ovarian cancers (HGSOC). This overall approach of SHG microscopy and image-based tissue engineered scaffolds affords decoupling the roles of matrix morphology, stiffness and cell genotype and affords hypothesis testing of the factors giving rise to disease progression and metastasis. Further, more established fabrication techniques cannot simultaneously reproduce both the 3D collagen fiber morphology and stiffness.
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