TY - JOUR
T1 - Horseradish peroxidase-crosslinked calcium-containing silk fibroin hydrogels as artificial matrices for bone cancer research
AU - Pierantoni, Lara
AU - Ribeiro, Viviana P.
AU - Costa, Lígia
AU - Pina, Sandra
AU - da Silva Morais, Alain
AU - Silva-Correia, Joana
AU - Kundu, Subhas C.
AU - Motta, Antonella
AU - Reis, Rui L.
AU - Oliveira, Joaquim M.
N1 - Funding Information:
L.P. thanks the International mobility program of the University of Trento, Italy. J.S.-C. and J.M.O. thank the Portuguese Foundation for Science and Technology (FCT) for the funds provided under the program Investigador FCT 2015 (IF/00115/2015 and IF/01285/2015, respectively). This research was funded by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000023). The project BAMOS (H2020-MSCA-RISE-2016-734156) funded by the European Union under the Horizon 2020 program, and the EU Framework Programme for Research and Innovation H2020 on FoReCaST (Grant Agreement No.668983), are also greatly acknowledged. V.P.R. acknowledge for the Junior Researcher contract (POCI-01-0145-FEDER-031367) attributed by the Portuguese Foundation for Science and Technology to Fun4TE project (PTDC/EMD-EMD/31367/2017). L.P. thanks C. Gonçalves for helping with analysis of rheology data, and T. Oliveira for the histology.
Funding Information:
L.P. thanks the International mobility program of the University of Trento, Italy. J.S.‐C. and J.M.O. thank the Portuguese Foundation for Science and Technology (FCT) for the funds provided under the program Investigador FCT 2015 (IF/00115/2015 and IF/01285/2015, respectively). This research was funded by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE‐01‐0145‐FEDER‐000023). The project BAMOS (H2020‐MSCA‐RISE‐2016‐734156) funded by the European Union under the Horizon 2020 program, and the EU Framework Programme for Research and Innovation H2020 on FoReCaST (Grant Agreement No.668983), are also greatly acknowledged. V.P.R. acknowledge for the Junior Researcher contract (POCI‐01‐0145‐FEDER‐031367) attributed by the Portuguese Foundation for Science and Technology to Fun4TE project (PTDC/EMD‐EMD/31367/2017). L.P. thanks C. Gonçalves for helping with analysis of rheology data, and T. Oliveira for the histology.
Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Bone
KW - Calcium
KW - Cancer
KW - Hydrogels
KW - Silk fibroin
UR - http://www.scopus.com/inward/record.url?scp=85100049383&partnerID=8YFLogxK
U2 - 10.1002/mabi.202000425
DO - 10.1002/mabi.202000425
M3 - Article
C2 - 33522095
SN - 1616-5187
VL - 21
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
IS - 4
M1 - 2000425
ER -