1. Recombinant Spider Silk Bioinks for Continuous Protein Release by Encapsulated Producer Cells.
- Author
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Trossmann VT, Heltmann-Meyer S, Amouei H, Wajant H, Horch RE, Steiner D, and Scheibel T
- Subjects
- Animals, Arthropod Proteins metabolism, HEK293 Cells, Humans, Hydrogels, Immunoglobulin G metabolism, Oligopeptides metabolism, Receptors, Tumor Necrosis Factor, Type II metabolism, Recombinant Proteins chemistry, Silk chemistry, Tissue Distribution, Biological Products, Spiders metabolism
- Abstract
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.
- Published
- 2022
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