No abstract

Hydrogels, being capable of mimicking the extracellular matrix composition of tissues, are greatly used as artificial matrices in tissue engineering applications. In this study, the generation of horseradish peroxidase (HRP)‐crosslinked silk fibroin (SF) hydrogels, using calcium peroxide as oxidizer is reported. The proposed fast forming calcium‐containing SF hydrogels spontaneously undergo SF conformational changes from random coil to β‐sheet during time, exhibiting ionic, and pH stimuli responsiveness. In vitro response shows calcium‐containing SF hydrogels’ encapsulation properties and their ability to promote SaOs‐2 tumor cells death after 10 days of culturing, upon complete β‐sheet conformation transition. Calcium‐containing SF hydrogels’ angiogenic potential investigated in an in ovo chick chorioallantoic membrane (CAM) assay, show a high number of converging blood vessels as compared to the negative control, although no endothelial cells infiltration is observed. The in vivo response evaluated in subcutaneous implantation in CD1 and nude NCD1 mice shows that calcium‐containing SF hydrogels are stable up to 6 weeks after implantation. However, an increased number of dead cells are also present in the surrounding tissue. The results suggest the potential of calcium‐containing SF hydrogels to be used as novel in situ therapeutics for bone cancer treatment applications, particularly to osteosarcoma.

Front Cover: This picture shows the in situ anti‐tumor therapeutic features of the developed calcium‐containing silk fibroin hydrogels cross‐linked in the presence of calcium peroxide and horseradish peroxidase. These are characterized by the fast gelation, compacted porous microstructure and slow drug release profile. They induced the death of encapsulated osteosarcoma cells after 10 days of culture. In in vivo studies, the calciumcontaining silk fibroin hydrogels inhibited angiogenesis and induced cells death and opening up new possible applications for bone cancer treatment. This is reported by Lara Pierantoni, Viviana P. Ribeiro, Lígia Costa, Sandra Pina, Alain da Silva Morais, Joana Silva‐Correia, Subhas C. Kundu, Antonella Motta, Rui L. Reis, Joaquim M. Oliveira in article 2000425.

No abstract

Breast cancer is still the leading cause of women's death due to relapse and metastasis. In vitro tumor models are considered reliable tools for drug screening and understanding cancer‐driving mechanisms due to the possibility of mimicking tumor heterogeneity. Herein, a 3D breast cancer model (3D‐BCM) is developed based on enzymatically‐crosslinked silk fibroin (eSF) hydrogels. Human MCF7 breast cancer cells are encapsulated into eSF hydrogels, with and without human mammary fibroblasts. The spontaneously occurring conformational change from random coil to β‐sheet is correlated with increased eSF hydrogels’ stiffness over time. Moreover, mechanical properties analysis confirms that the cells can modify the stiffness of the hydrogels, mimicking the microenvironment stiffening occurring in vivo. Fibroblasts support cancer cells growth and assembly in the eSF hydrogels up to 14 days of culture. Co‐cultured 3D‐BCM exhibits an upregulated expression of genes related to extracellular matrix remodeling and fibroblast activation. The 3D‐BCM is subjected to doxorubicin and paclitaxel treatments, showing differential drug response. Overall, these results suggest that the co‐culture of breast cancer cells and fibroblasts in eSF hydrogels allow the development of a mimetic in vitro platform to study cancer progression. This opens up new research avenues to investigate novel molecular targets for anti‐cancer therapy.