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Cellular Encapsulation in 3D Hydrogels for Tissue Engineering
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Engineering Cyborg Pathogens through Intracellular Hydrogelation.

Shahid Khan1, Pin-Ru Lin1, Cheemeng Tan1

  • 1Department of Biomedical Engineering, University of California, Davis, Davis, California 95616, United States.

ACS Synthetic Biology
|October 16, 2024
PubMed
Summary
This summary is machine-generated.

Researchers engineered cyborg pathogens from common bacteria like Pseudomonas aeruginosa and Staphylococcus aureus. These metabolically active, non-replicating cyborg pathogens show potential for biomedical applications such as drug delivery and immunotherapy.

Keywords:
Pseudomonas aeruginosaStaphylococcus aureuscyborg pathogenintracellular hydrogelationmacrophagessynthetic biology

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Area of Science:

  • Synthetic biology
  • Biomedical engineering
  • Microbiology

Background:

  • Synthetic biology utilizes living or nonliving cell chassis; recent advances created cyborg bacteria via intracellular hydrogelation.
  • Previous cyborg cell engineering focused on non-pathogenic Escherichia coli.
  • Extending this to pathogenic bacteria offers novel biomedical applications by leveraging their inherent properties.

Purpose of the Study:

  • To generalize the cyborg cell approach to pathogenic bacteria, specifically Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae.
  • To investigate the effects of hydrogel concentration on cyborg pathogen metabolism, replication, and intracellular gelation.
  • To evaluate the interaction of cyborg pathogens with macrophages, comparing uptake and cellular response to wild-type pathogens.

Main Methods:

  • Engineered cyborg pathogens using intracellular hydrogelation in target bacterial strains.
  • Assessed impacts of varying hydrogel concentrations on pathogen metabolism and replication.
  • Utilized confocal microscopy and real-time PCR to compare macrophage uptake of cyborg versus wild-type pathogens.
  • Analyzed macrophage phenotypic responses post-uptake of cyborg pathogens.

Main Results:

  • Successfully synthesized cyborg pathogens from P. aeruginosa, S. aureus, and K. pneumoniae.
  • Determined optimal hydrogel concentrations for effective intracellular gelation without compromising essential cellular functions.
  • Demonstrated comparable macrophage uptake rates for cyborg and wild-type pathogens.
  • Observed similar macrophage phenotypic responses to both cyborg and wild-type pathogens.

Conclusions:

  • The intracellular hydrogelation method is now applicable to bacterial pathogens beyond E. coli.
  • Engineered cyborg pathogens maintain key interactions with host immune cells like macrophages.
  • These novel cyborg pathogens present a versatile platform for advanced biomedical applications, including drug delivery and immunotherapy.