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Recombinant Spider Silk Bioinks for Continuous Protein Release by Encapsulated Producer Cells
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    Recombinant Spider Silk Bioinks for Continuous Protein Release by Encapsulated Producer Cells
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    • Vanessa T. Trossmann
      Vanessa T. Trossmann
      Lehrstuhl Biomaterialien, Fakultät für Ingenieurswissenschaften, Universität Bayreuth, Prof.-Rüdiger-Bormann-Str. 1, Bayreuth 95447, Germany
    • Stefanie Heltmann-Meyer
      Stefanie Heltmann-Meyer
      Department of Plastic and Hand Surgery and Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital of Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Krankenhaus-Str. 12, Erlangen 91054, Germany
    • Hanna Amouei
      Hanna Amouei
      Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital of Würzburg, Grombühl-Str. 12, Würzburg 97080, Germany
      More by Hanna Amouei
    • Harald Wajant
      Harald Wajant
      Division of Molecular Internal Medicine, Department of Internal Medicine II, University Hospital of Würzburg, Grombühl-Str. 12, Würzburg 97080, Germany
    • Raymund E. Horch
      Raymund E. Horch
      Department of Plastic and Hand Surgery and Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital of Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Krankenhaus-Str. 12, Erlangen 91054, Germany
    • Dominik Steiner*
      Dominik Steiner
      Department of Plastic and Hand Surgery and Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital of Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Krankenhaus-Str. 12, Erlangen 91054, Germany
      *Email: [email protected]. Phone: +49 (0) 9131 85 33 296.
    • Thomas Scheibel*
      Thomas Scheibel
      Lehrstuhl Biomaterialien, Fakultät für Ingenieurswissenschaften, Universität Bayreuth, Prof.-Rüdiger-Bormann-Str. 1, Bayreuth 95447, Germany
      Bayreuther Zentrum für Kolloide und Grenzflächen (BZKG), Bayerisches Polymerinstitut (BPI), Bayreuther Zentrum für Molekulare Biowissenschaften (BZMB), Bayreuther Materialzentrum (BayMAT), Universität Bayreuth, Universitäts-Str. 30, Bayreuth 95447, Germany
      *Email: [email protected]. Phone: +49 (0) 921 55 6700
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    Biomacromolecules

    Cite this: Biomacromolecules 2022, 23, 10, 4427–4437
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    https://doi.org/10.1021/acs.biomac.2c00971
    Published September 6, 2022
    Copyright © 2022 The Authors. Published by American Chemical Society

    Abstract

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    Targeted therapies using biopharmaceuticals are of growing clinical importance in disease treatment. Currently, there are several limitations of protein-based therapeutics (biologicals), including suboptimal biodistribution, lack of stability, and systemic side effects. A promising approach to overcoming these limitations could be a therapeutic cell-loaded 3D construct consisting of a suitable matrix component that harbors producer cells continuously secreting the biological of interest. Here, the recombinant spider silk proteins eADF4(C16), eADF4(C16)-RGD, and eADF4(C16)-RGE have been processed together with HEK293 producer cells stably secreting the highly traceable reporter biological TNFR2-Fc-GpL, a fusion protein consisting of the extracellular domain of TNFR2, the Fc domain of human IgG1, and the luciferase of Gaussia princeps as a reporter domain. eADF4(C16) and eADF4(C16)-RGD hydrogels provide structural and mechanical support, promote HEK293 cell growth, and allow fusion protein production by the latter. Bioink-captured HEK293 producer cells continuously release functional TNFR2-Fc-GpL over 14 days. Thus, the combination of biocompatible, printable spider silk bioinks with drug-producing cells is promising for generating implantable 3D constructs for continuous targeted therapy.

    Copyright © 2022 The Authors. Published by American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.biomac.2c00971.

    • Recovery of spider silk hydrogels and bioinks (PDF)

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    Cited By

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    This article is cited by 10 publications.

    1. Dilip Kumar Chandra, Rui L. Reis, Subhas C. Kundu, Awanish Kumar, Chinmaya Mahapatra. Nanomaterials-Based Hybrid Bioink Platforms in Advancing 3D Bioprinting Technologies for Regenerative Medicine. ACS Biomaterials Science & Engineering 2024, 10 (7) , 4145-4174. https://doi.org/10.1021/acsbiomaterials.4c00166
    2. Shangrong Hu, Sijing Wan, Xinyu Zhang, Xianzhong Wang, Liwen Guan, Yuxin Ge, Yan Li, Jianlin Luo, Bin Tang. Structure, production and application of spider silks. International Journal of Biological Macromolecules 2025, 309 , 142939. https://doi.org/10.1016/j.ijbiomac.2025.142939
    3. Xuen J. Ng, Tilman U. Esser, Vanessa T. Trossmann, Christoph Rudisch, Maren Fiedler, Kaveh Roshanbinfar, Zan Lamberger, Philipp Stahlhut, Gregor Lang, Thomas Scheibel, Felix B. Engel. Enhancing Form Stability: Shrink‐Resistant Hydrogels Made of Interpenetrating Networks of Recombinant Spider Silk and Collagen‐I. Advanced Healthcare Materials 2025, 14 (12) https://doi.org/10.1002/adhm.202500311
    4. Cong Wang, Qi Zhang, Hanbai Wu, Shuai Zhang, Xiong Zhou, Min Li, Yuhan Chen, Wei Liu, Min Du, Jun Fan, Furong Chen, Jinlian Hu. Rapidly Forming Recombinant Miniature Spidroins Hydrogels Composed of Nanofibrils with Tunable Mechanical Properties for Bio 3D Printing and Biomimetic Cellular Scaffolds. Advanced Functional Materials 2025, 35 (17) https://doi.org/10.1002/adfm.202420059
    5. Justus Osterloh, Stefanie Heltmann-Meyer, Vanessa T. Trossmann, Aijia Cai, Yvonne Kulicke, Klara Terörde, Celena A. Sörgel, Isabell Lang, Harald Wajant, Thomas Scheibel, Tobias Fey, Dominik Steiner, Andreas Arkudas, Raymund E. Horch. In Vivo Vascularization of Cell-Supplemented Spider Silk-Based Hydrogels in the Arteriovenous Loop Model. Biomimetics 2025, 10 (2) , 117. https://doi.org/10.3390/biomimetics10020117
    6. Tina Arndt, Urmimala Chatterjee, Olga Shilkova, Juanita Francis, Johan Lundkvist, Daniel Johansson, Benjamin Schmuck, Gabriele Greco, Åsa Ekblad Nordberg, Yan Li, Lars U Wahlberg, Maud Langton, Jan Johansson, Cecilia Götherström, Anna Rising. Tuneable Recombinant Spider Silk Protein Hydrogels for Drug Release and 3D Cell Culture. Advanced Functional Materials 2024, 34 (35) https://doi.org/10.1002/adfm.202303622
    7. Dalia Dranseike, Yusuke Ota, Thomas G.W. Edwardson, Elia A. Guzzi, Mao Hori, Zrinka Raguz Nakic, Dhananjay V. Deshmukh, Mikail D. Levasseur, Kevin Mattli, Christina M. Tringides, Jiangtao Zhou, Donald Hilvert, Christin Peters, Mark W. Tibbitt. Designed modular protein hydrogels for biofabrication. Acta Biomaterialia 2024, 177 , 107-117. https://doi.org/10.1016/j.actbio.2024.02.019
    8. Vanessa T. Trossmann, Thomas Scheibel. Spider silk and blend biomaterials: recent advances and future opportunities. 2024, 133-190. https://doi.org/10.1016/B978-0-323-96017-5.00005-4
    9. Eduarda P. Oliveira, F. Raquel Maia, Rui L. Reis, Joaquim M. Oliveira. Engineering enzymatic- and photo-crosslinked silk-based hydrogels for regenerative medicine. 2024, 221-239. https://doi.org/10.1016/B978-0-323-96017-5.00009-1
    10. Vanessa Tanja Trossmann, Thomas Scheibel. Design of Recombinant Spider Silk Proteins for Cell Type Specific Binding. Advanced Healthcare Materials 2023, 12 (9) https://doi.org/10.1002/adhm.202202660

    Biomacromolecules

    Cite this: Biomacromolecules 2022, 23, 10, 4427–4437
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.biomac.2c00971
    Published September 6, 2022
    Copyright © 2022 The Authors. Published by American Chemical Society

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