Horseradish peroxidase-crosslinked calcium-containing silk fibroin hydrogels as artificial matrices for bone cancer research
"Online ahead of print" Hydrogels, being capable of mimicking the extracellular matrix composition of tissues, are greatly used as artificial matrices in tissue engineering applications. In this study, we report the generation of horseradish peroxidase (HRP)-crosslinked silk fibroin (SF) h...
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| Veröffentlicht in: | Macromolecular bioscience 2021-04, Vol.21 (4), p.2000425(1)-2000425(7) |
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| creator | Pierantoni, Lara Ribeiro, Viviana Pinto Costa, Lígia Francisca Rodrigues Pina, Sandra Cristina Almeida da Silva Morais, Alain Silva-Correia, Joana Kundu, Subhas C Motta, Antonella Reis, R. L. Oliveira, J. M. |
| description | "Online ahead of print"
Hydrogels, being capable of mimicking the extracellular matrix composition of tissues, are greatly used as artificial matrices in tissue engineering applications. In this study, we report the generation of horseradish peroxidase (HRP)-crosslinked silk fibroin (SF) hydrogels, using calcium peroxide as oxidizer. 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 hydrogelsâ 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 hydrogelsâ 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.
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-MSCARISE-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). |
| doi_str_mv | 10.1002/mabi.202000425 |
| format | Article |
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Hydrogels, being capable of mimicking the extracellular matrix composition of tissues, are greatly used as artificial matrices in tissue engineering applications. In this study, we report the generation of horseradish peroxidase (HRP)-crosslinked silk fibroin (SF) hydrogels, using calcium peroxide as oxidizer. 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 hydrogelsâ 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 hydrogelsâ 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.
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-MSCARISE-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).</description><identifier>ISSN: 1616-5187</identifier><identifier>EISSN: 1616-5195</identifier><identifier>DOI: 10.1002/mabi.202000425</identifier><identifier>PMID: 33522095</identifier><language>eng</language><publisher>Germany: Wiley</publisher><subject>Angiogenesis ; Animals ; Biomedical materials ; Blood vessels ; Bone ; Bone and Bones - metabolism ; Bone cancer ; Bone composition ; Bone Neoplasms - metabolism ; Bone Neoplasms - pathology ; Calcium ; Cancer ; Cancer research ; Cell death ; Cell Line, Tumor ; Chorioallantoic membrane ; Chorioallantoic Membrane - metabolism ; Coils ; Conformation ; Crosslinking ; Endothelial cells ; Extracellular matrix ; Fibroins - chemistry ; Horseradish peroxidase ; Horseradish Peroxidase - chemistry ; Humans ; Hydrogels ; Hydrogels - chemistry ; Hydrogen-Ion Concentration ; Implantation ; Metastases ; Mice ; Mimicry ; Neovascularization, Pathologic ; Osteosarcoma ; Oxidizing agents ; Peroxidase ; Peroxide ; Protein Conformation ; Random coil ; Science & Technology ; Silk ; Silk - metabolism ; Silk Fibroin ; Surgical implants ; Tissue Engineering ; Tumor cells</subject><ispartof>Macromolecular bioscience, 2021-04, Vol.21 (4), p.2000425(1)-2000425(7)</ispartof><rights>2021 Wiley‐VCH GmbH</rights><rights>2021 Wiley-VCH GmbH.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5415-24f03ff916f8a1c10da0d5c75bdc0c5ce54dbf4322b01fd84543eae0d4f503793</citedby><cites>FETCH-LOGICAL-c5415-24f03ff916f8a1c10da0d5c75bdc0c5ce54dbf4322b01fd84543eae0d4f503793</cites><orcidid>0000-0002-4361-1253 ; 0000-0003-1312-3109 ; 0000-0003-4893-6863 ; 0000-0002-7170-2291 ; 0000-0001-5057-0819 ; 0000-0001-8618-7889 ; 0000-0001-7052-8837 ; 0000-0002-3679-0759 ; 0000-0002-4295-6129</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmabi.202000425$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmabi.202000425$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33522095$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pierantoni, Lara</creatorcontrib><creatorcontrib>Ribeiro, Viviana Pinto</creatorcontrib><creatorcontrib>Costa, Lígia Francisca Rodrigues</creatorcontrib><creatorcontrib>Pina, Sandra Cristina Almeida</creatorcontrib><creatorcontrib>da Silva Morais, Alain</creatorcontrib><creatorcontrib>Silva-Correia, Joana</creatorcontrib><creatorcontrib>Kundu, Subhas C</creatorcontrib><creatorcontrib>Motta, Antonella</creatorcontrib><creatorcontrib>Reis, R. L.</creatorcontrib><creatorcontrib>Oliveira, J. M.</creatorcontrib><title>Horseradish peroxidase-crosslinked calcium-containing silk fibroin hydrogels as artificial matrices for bone cancer research</title><title>Macromolecular bioscience</title><addtitle>Macromol Biosci</addtitle><description>"Online ahead of print"
Hydrogels, being capable of mimicking the extracellular matrix composition of tissues, are greatly used as artificial matrices in tissue engineering applications. In this study, we report the generation of horseradish peroxidase (HRP)-crosslinked silk fibroin (SF) hydrogels, using calcium peroxide as oxidizer. 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 hydrogelsâ 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 hydrogelsâ 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.
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-MSCARISE-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).</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biomedical materials</subject><subject>Blood vessels</subject><subject>Bone</subject><subject>Bone and Bones - metabolism</subject><subject>Bone cancer</subject><subject>Bone composition</subject><subject>Bone Neoplasms - metabolism</subject><subject>Bone Neoplasms - pathology</subject><subject>Calcium</subject><subject>Cancer</subject><subject>Cancer research</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Chorioallantoic membrane</subject><subject>Chorioallantoic Membrane - metabolism</subject><subject>Coils</subject><subject>Conformation</subject><subject>Crosslinking</subject><subject>Endothelial cells</subject><subject>Extracellular matrix</subject><subject>Fibroins - chemistry</subject><subject>Horseradish peroxidase</subject><subject>Horseradish Peroxidase - chemistry</subject><subject>Humans</subject><subject>Hydrogels</subject><subject>Hydrogels - chemistry</subject><subject>Hydrogen-Ion Concentration</subject><subject>Implantation</subject><subject>Metastases</subject><subject>Mice</subject><subject>Mimicry</subject><subject>Neovascularization, Pathologic</subject><subject>Osteosarcoma</subject><subject>Oxidizing agents</subject><subject>Peroxidase</subject><subject>Peroxide</subject><subject>Protein Conformation</subject><subject>Random coil</subject><subject>Science & Technology</subject><subject>Silk</subject><subject>Silk - metabolism</subject><subject>Silk Fibroin</subject><subject>Surgical implants</subject><subject>Tissue Engineering</subject><subject>Tumor cells</subject><issn>1616-5187</issn><issn>1616-5195</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQRi0EomXhyhFZ4sIly9iON8mxVEArFXGBs-XY465bJ17GCbASP560W1aIC5JH9uHNG2s-xl4KWAsA-XawfVxLkABQS_2InYqN2FRadPrx8d02J-xZKTcAomk7-ZSdKKWlhE6fsl8XmQqS9bFs-Q4p_4zeFqwc5VJSHG_Rc2eTi_NQuTxONo5xvOYlplseYk85jny795SvMRVul0NTDNFFm_hgJ4oOCw-ZeJ9HXEyjQ-KEBS257XP2JNhU8MXDvWJfP7z_cn5RXX3-eHl-dlU5XQtdyTqACqETm9Ba4QR4C167RvfegdMOde37UCspexDBt7WuFVoEXwcNqunUir05eHeUv81YJjPE4jAlO2Kei5F1u8zRzT36-h_0Js80Lr8zUguppBJLrdj6QN2viTCYHcXB0t4IMHe5mLtczDGXpeHVg3buB_RH_E8QC9AdgB8x4f4_OvPp7N3l33J-6CVn7c4Qfo9lssWIVkrTALRK_QYJL6Zc</recordid><startdate>202104</startdate><enddate>202104</enddate><creator>Pierantoni, Lara</creator><creator>Ribeiro, Viviana Pinto</creator><creator>Costa, Lígia Francisca Rodrigues</creator><creator>Pina, Sandra Cristina Almeida</creator><creator>da Silva Morais, Alain</creator><creator>Silva-Correia, Joana</creator><creator>Kundu, Subhas C</creator><creator>Motta, Antonella</creator><creator>Reis, R. L.</creator><creator>Oliveira, J. M.</creator><general>Wiley</general><general>Wiley Subscription Services, Inc</general><scope>RCLKO</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4361-1253</orcidid><orcidid>https://orcid.org/0000-0003-1312-3109</orcidid><orcidid>https://orcid.org/0000-0003-4893-6863</orcidid><orcidid>https://orcid.org/0000-0002-7170-2291</orcidid><orcidid>https://orcid.org/0000-0001-5057-0819</orcidid><orcidid>https://orcid.org/0000-0001-8618-7889</orcidid><orcidid>https://orcid.org/0000-0001-7052-8837</orcidid><orcidid>https://orcid.org/0000-0002-3679-0759</orcidid><orcidid>https://orcid.org/0000-0002-4295-6129</orcidid></search><sort><creationdate>202104</creationdate><title>Horseradish peroxidase-crosslinked calcium-containing silk fibroin hydrogels as artificial matrices for bone cancer research</title><author>Pierantoni, Lara ; Ribeiro, Viviana Pinto ; Costa, Lígia Francisca Rodrigues ; Pina, Sandra Cristina Almeida ; da Silva Morais, Alain ; Silva-Correia, Joana ; Kundu, Subhas C ; Motta, Antonella ; Reis, R. L. ; Oliveira, J. M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5415-24f03ff916f8a1c10da0d5c75bdc0c5ce54dbf4322b01fd84543eae0d4f503793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Biomedical materials</topic><topic>Blood vessels</topic><topic>Bone</topic><topic>Bone and Bones - metabolism</topic><topic>Bone cancer</topic><topic>Bone composition</topic><topic>Bone Neoplasms - metabolism</topic><topic>Bone Neoplasms - pathology</topic><topic>Calcium</topic><topic>Cancer</topic><topic>Cancer research</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Chorioallantoic membrane</topic><topic>Chorioallantoic Membrane - metabolism</topic><topic>Coils</topic><topic>Conformation</topic><topic>Crosslinking</topic><topic>Endothelial cells</topic><topic>Extracellular matrix</topic><topic>Fibroins - chemistry</topic><topic>Horseradish peroxidase</topic><topic>Horseradish Peroxidase - chemistry</topic><topic>Humans</topic><topic>Hydrogels</topic><topic>Hydrogels - chemistry</topic><topic>Hydrogen-Ion Concentration</topic><topic>Implantation</topic><topic>Metastases</topic><topic>Mice</topic><topic>Mimicry</topic><topic>Neovascularization, Pathologic</topic><topic>Osteosarcoma</topic><topic>Oxidizing agents</topic><topic>Peroxidase</topic><topic>Peroxide</topic><topic>Protein Conformation</topic><topic>Random coil</topic><topic>Science & Technology</topic><topic>Silk</topic><topic>Silk - metabolism</topic><topic>Silk Fibroin</topic><topic>Surgical implants</topic><topic>Tissue Engineering</topic><topic>Tumor cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pierantoni, Lara</creatorcontrib><creatorcontrib>Ribeiro, Viviana Pinto</creatorcontrib><creatorcontrib>Costa, Lígia Francisca Rodrigues</creatorcontrib><creatorcontrib>Pina, Sandra Cristina Almeida</creatorcontrib><creatorcontrib>da Silva Morais, Alain</creatorcontrib><creatorcontrib>Silva-Correia, Joana</creatorcontrib><creatorcontrib>Kundu, Subhas C</creatorcontrib><creatorcontrib>Motta, Antonella</creatorcontrib><creatorcontrib>Reis, R. L.</creatorcontrib><creatorcontrib>Oliveira, J. M.</creatorcontrib><collection>RCAAP open access repository</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Macromolecular bioscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pierantoni, Lara</au><au>Ribeiro, Viviana Pinto</au><au>Costa, Lígia Francisca Rodrigues</au><au>Pina, Sandra Cristina Almeida</au><au>da Silva Morais, Alain</au><au>Silva-Correia, Joana</au><au>Kundu, Subhas C</au><au>Motta, Antonella</au><au>Reis, R. L.</au><au>Oliveira, J. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Horseradish peroxidase-crosslinked calcium-containing silk fibroin hydrogels as artificial matrices for bone cancer research</atitle><jtitle>Macromolecular bioscience</jtitle><addtitle>Macromol Biosci</addtitle><date>2021-04</date><risdate>2021</risdate><volume>21</volume><issue>4</issue><spage>2000425(1)</spage><epage>2000425(7)</epage><pages>2000425(1)-2000425(7)</pages><issn>1616-5187</issn><eissn>1616-5195</eissn><abstract>"Online ahead of print"
Hydrogels, being capable of mimicking the extracellular matrix composition of tissues, are greatly used as artificial matrices in tissue engineering applications. In this study, we report the generation of horseradish peroxidase (HRP)-crosslinked silk fibroin (SF) hydrogels, using calcium peroxide as oxidizer. 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 hydrogelsâ 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 hydrogelsâ 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.
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-MSCARISE-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).</abstract><cop>Germany</cop><pub>Wiley</pub><pmid>33522095</pmid><doi>10.1002/mabi.202000425</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-4361-1253</orcidid><orcidid>https://orcid.org/0000-0003-1312-3109</orcidid><orcidid>https://orcid.org/0000-0003-4893-6863</orcidid><orcidid>https://orcid.org/0000-0002-7170-2291</orcidid><orcidid>https://orcid.org/0000-0001-5057-0819</orcidid><orcidid>https://orcid.org/0000-0001-8618-7889</orcidid><orcidid>https://orcid.org/0000-0001-7052-8837</orcidid><orcidid>https://orcid.org/0000-0002-3679-0759</orcidid><orcidid>https://orcid.org/0000-0002-4295-6129</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Angiogenesis Animals Biomedical materials Blood vessels Bone Bone and Bones - metabolism Bone cancer Bone composition Bone Neoplasms - metabolism Bone Neoplasms - pathology Calcium Cancer Cancer research Cell death Cell Line, Tumor Chorioallantoic membrane Chorioallantoic Membrane - metabolism Coils Conformation Crosslinking Endothelial cells Extracellular matrix Fibroins - chemistry Horseradish peroxidase Horseradish Peroxidase - chemistry Humans Hydrogels Hydrogels - chemistry Hydrogen-Ion Concentration Implantation Metastases Mice Mimicry Neovascularization, Pathologic Osteosarcoma Oxidizing agents Peroxidase Peroxide Protein Conformation Random coil Science & Technology Silk Silk - metabolism Silk Fibroin Surgical implants Tissue Engineering Tumor cells |
| title | Horseradish peroxidase-crosslinked calcium-containing silk fibroin hydrogels as artificial matrices for bone cancer research |
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