作者: Elke Kaemmerer , Ferry P.W. Melchels , Boris M. Holzapfel , Tobias Meckel , Dietmar W. Hutmacher
DOI: 10.1016/J.ACTBIO.2014.02.035
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摘要: Modern cancer research requires physiological, three-dimensional (3-D) cell culture platforms, wherein the physical and chemical characteristics of extracellular matrix (ECM) can be modified. In this study, gelatine methacrylamide (GelMA)-based hydrogels were characterized established as in vitro vivo spheroid-based models for ovarian cancer, reflecting advanced disease stage patients, with accumulation multicellular spheroids tumour fluid (ascites). Polymer concentration (2.5-7% w/v) strongly influenced hydrogel stiffness (0.5±0.2kPa to 9.0±1.8kPa) but had little effect on solute diffusion. The diffusion coefficient 70kDa fluorescein isothiocyanate (FITC)-labelled dextran 7% GelMA-based was only 2.3 times slower compared water. Hydrogels medium (5% w/v GelMA) (3.4kPa) allowed spheroid formation high proliferation metabolic rates. inhibition metalloproteinases consequently ECM degradability reduced incorporation components laminin-411 hyaluronic acid further stimulated growth within hydrogels. feasibility pre-cultured carriers an animal model proven led development metastasis. These tumours sensitive treatment anti-cancer drug paclitaxel, not integrin antagonist ATN-161. While paclitaxel its combination ATN-161 resulted a response 33-37.8%, alone no peritoneal spread. semi-synthetic biomaterial GelMA combines relevant natural cues tunable properties, providing alternative, bioengineered 3-D systems.