| 2. |
- Calitz, Carlemi, et al.
(författare)
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Influence of extracellular matrix composition on tumour cell behaviour in a biomimetic in vitro model for hepatocellular carcinoma
- 2023
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The tumor micro-environment (TME) of hepatocellular carcinoma (HCC) consists out of cirrhotic liver tissue and is characterized by an extensive deposition of extracellular matrix proteins (ECM). The evolution from a reversible fibrotic state to end-stage of liver disease, namely cirrhosis, is characterized by an increased deposition of ECM, as well as changes in the exact ECM composition, which both contribute to an increased liver stiffness and can alter tumor phenotype. The goal of this study was to assess how changes in matrix composition and stiffness influence tumor behavior. HCC-cell lines were grown in a biomimetic hydrogel model resembling the stiffness and composition of a fibrotic or cirrhotic liver. When HCC-cells were grown in a matrix resembling a cirrhotic liver, they increased proliferation and protein content, compared to those grown in a fibrotic environment. Tumour nodules spontaneously formed outside the gels, which appeared earlier in cirrhotic conditions and were significantly larger compared to those found outside fibrotic gels. These tumor nodules had an increased expression of markers related to epithelial-to-mesenchymal transition (EMT), when comparing cirrhotic to fibrotic gels. HCC-cells grown in cirrhotic gels were also more resistant to doxorubicin compared with those grown in fibrotic gels or in 2D. Therefore, altering ECM composition affects tumor behavior, for instance by increasing pro-metastatic potential, inducing EMT and reducing response to chemotherapy.
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| 3. |
- Rosenquist, Jenny, et al.
(författare)
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An Injectable, Shape-Retaining Collagen Hydrogel Cross-linked Using Thiol-Maleimide Click Chemistry for Sealing Corneal Perforations
- 2023
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 15:29, s. 34407-34418
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Tidskriftsartikel (refereegranskat)abstract
- Injectable hydrogels show great promise in developingnovel regenerativemedicine solutions and present advantages for minimally invasive applications.Hydrogels based on extracellular matrix components, such as collagen,have the benefits of cell adhesiveness, biocompatibility, and degradabilityby enzymes. However, to date, reported collagen hydrogels possesssevere shortcomings, such as nonbiocompatible cross-linking chemistry,significant swelling, limited range of mechanical properties, or gelationkinetics unsuitable for in vivo injection. To solvethese issues, we report the design and characterization of an injectablecollagen hydrogel based on covalently modified acetyl thiol collagencross-linked using thiol-maleimide click chemistry. The hydrogel isinjectable for up to 72 h after preparation, shows no noticeable swelling,is transparent, can be molded in situ, and retainsits shape in solution for at least one year. Notably, the hydrogelmechanical properties can be fine-tuned by simply adjusting the reactantstoichiometries, which to date was only reported for synthetic polymerhydrogels. The biocompatibility of the hydrogel is demonstrated in vitro using human corneal epithelial cells, which maintainviability and proliferation on the hydrogels for at least seven days.Furthermore, the developed hydrogel showed an adhesion strength onsoft tissues similar to fibrin glue. Additionally, the developed hydrogelcan be used as a sealant for repairing corneal perforations and canpotentially alleviate the off-label use of cyanoacrylate tissue adhesivefor repairing corneal perforations. Taken together, these characteristicsshow the potential of the thiol collagen hydrogel for future use asa prefabricated implant, injectable filler, or as sealant for cornealrepair and regeneration.
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