Recombinant Spider Silk Bioinks for Continuous Protein Release by Encapsulated Producer Cells

Biomacromolecules. 2022 Oct 10;23(10):4427-4437. doi: 10.1021/acs.biomac.2c00971. Epub 2022 Sep 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthropod Proteins / metabolism
  • Biological Products*
  • HEK293 Cells
  • Humans
  • Hydrogels
  • Immunoglobulin G / metabolism
  • Oligopeptides / metabolism
  • Receptors, Tumor Necrosis Factor, Type II / metabolism
  • Recombinant Proteins / chemistry
  • Silk / chemistry
  • Spiders* / metabolism
  • Tissue Distribution

Substances

  • Arthropod Proteins
  • Biological Products
  • Hydrogels
  • Immunoglobulin G
  • Oligopeptides
  • Receptors, Tumor Necrosis Factor, Type II
  • Recombinant Proteins
  • Silk