|
Authors
|
Sievers-Liebschner, J.; Welzel, P. B.; Fusenig, M.; Sturm, L.; Pette, D.; Wagermaier, W.; Fischbach, C.; Fratzl, P.; Werner, C.
|
|
Title
|
Mineralized cryogel/hydrogel constructs to recapitulate early breast cancer bone metastasis in vitro
|
|
Date
|
27.01.2026
|
|
Number
|
0
|
|
Abstract
|
Initial stages of bone colonization by breast cancer cells are critical for metastasis, but current in vitro models cannot decipher the microenvironmental cues involved. Therefore, a biphasic hydrogel model system is designed that recapitulates structural, biophysical, and biochemical components of the bone microenvironment to replicate early metastasis events. Breast cancer cells embedded within a glycosaminoglycan-based nanoporous hydrogel phase are traced as they colonize a directly adjacent macroporous cryogel compartment, precisely and selectively equipped with specific bone-like biomolecular signals and/or solution-deposited mineral crystals. Microscopic monitoring of the spatiotemporal cancer cell distributions yields colonization profiles that display the correlated effects of cell invasion, matrix interaction, and proliferation. MDA-MB-231 cells, but not MCF-7 cells, rapidly infiltrate the cryogel compartment at rates depending on the cross-linking degree of the hydrogel phase. Cryogel functionalization with adhesion-mediating peptide ligands enhances matrix interactions and survival/proliferation of the MDA-MB-231 cells. When combined with cryogel-released stromal cell-derived factor 1 (SDF-1), survival/proliferation are further amplified and additionally MDA-MB-231 cell invasion is promoted. The presence of deposited bone-like mineral strongly impedes these responses and is accompanied by characteristic alterations in distinct cellular gene-expression programs. The reported methodology may not only provide further mechanistic insights into early bone metastasis, but also facilitate the screening of anti-metastatic drugs.
|
|
Publisher
|
Wiley
|
|
Wikidata
|
|
|
Citation
|
Advanced Science 13 (2026) e19798
|
|
DOI
|
https://doi.org/10.1002/advs.202519798
|
|
Tags
|
|
