A TISSUE ENGINEERED TRIPHASIC MODEL TO INVESTIGATE BREAST CANCER BONE METASTASIS

Date

2026-1-19

Author

Güngör, Ecem Öykü

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Tissue-engineered 3D systems provide physiologically relevant models for the investigation of breast cancer bone metastasis. In this study, a triphasic in vitro model was developed to recapitulate invasive breast cancer (Phase I), vessel matrix (Phase II), and healthy bone tissue (Phase III). GelMA hydrogels (5%, 7.5%, 10%, and 15%, w/v) were characterized to model breast and vessel matrices. 15% GelMA (15G) and 10% GelMA (10G) with compressive moduli of 5.9±0.6 kPa and 3.2±0.6 kPa were chosen to mimic the breast and vessel matrices, respectively. For the bone phase, GelMA/HAp composite hydrogels having 5%, 10%, and 15% (w/w) HAp in 15% GelMA were evaluated, and 15% GelMA with 15% HAp (15G15H) with a compressive modulus of 8.6±1.1 kPa was chosen for the bone matrix. A breast tumor was established by encapsulating spheroids of MDA-MB-231 and MCF10A cells within 15G GelMA. The vascular phase consisted of ADSCs and HUVECs in 10G GelMA, whereas the bone phase contained hFOBs embedded in 15G15H GelMA/HAp hydrogel. The model was assembled sequentially, starting with bone maturation for 7 days, followed by vascular integration and an additional 7-day incubation prior to breast cancer incorporation. Tumor cell migration was investigated using CellTracker labeled MDA-MB-231 cells after integration of the breast cancer phase. It was found that the vascular compartment critically directed tumor cells toward the bone region, while the presence of the bone matrix significantly influenced cancer cell metastasis. Overall, the platform enables investigation of transendothelial migration toward bone tissue and provides a valuable tool for cancer studies.

Subject Keywords

Kanser Modeli, Hidrojel, Meme Kanseri, Sferoid, Metastaz

URI

https://hdl.handle.net/11511/118466

Collections

Graduate School of Natural and Applied Sciences, Thesis