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Controlled Release of Microorganisms from Engineered Living Materials

Manivannan Sivaperuman Kalairaj1, Iris George2, Sasha M George3

  • 1Department of Biomedical Engineering, Texas A&M University, College Station, Texas 77843, United States.

ACS Applied Materials & Interfaces
|July 8, 2025
PubMed

Insights

Engineered living materials release probiotics through a novel hydrogel fracture mechanism. This approach ensures sustained delivery of therapeutically relevant doses for over 100 days, overcoming previous limitations in probiotic persistence.

Area of Science:

  • Biomaterials Science
  • Microbiology
  • Synthetic Biology

Background:

  • Probiotics modulate the microbiome and immune response for therapeutic benefits.
  • Effective probiotic therapy requires sustained persistence at the target site.
  • Existing methods lack biomaterials for sustained, clinically relevant probiotic release.

Purpose of the Study:

  • To develop a novel biomaterial for sustained release of metabolically active probiotics.
  • To establish a generic mechanism for controlled microbial delivery using engineered living materials.
  • To demonstrate zero-order release kinetics for probiotic delivery.

Main Methods:

  • Encapsulating stiff probiotic microorganisms within less stiff hydrogels.
  • Utilizing microbial proliferation to induce hydrogel fracture and subsequent release.
  • Characterizing release kinetics and dose-response by varying initial cell loading and matrix properties.
  • Testing controlled release across diverse microbial types (Gram-negative, Gram-positive, fungal).

Main Results:

  • Engineered living materials (ELMs) release >10^8 colony-forming-units (CFUs) of Escherichia coli within 2 hours.
  • Sustained probiotic release was observed for at least 100 days.
  • Release kinetics followed zero-order release, indicating a constant rate of delivery.
  • Microbial release was controllable over three orders of magnitude by adjusting loading and matrix mechanics.
  • Demonstrated controlled release of various probiotic types from multiple hydrogel matrices.

Conclusions:

  • A novel hydrogel fracture mechanism enables sustained and controlled release of probiotics.
  • This engineered living material approach overcomes limitations in achieving probiotic persistence for therapeutic applications.
  • The mechanical release mechanism offers a versatile platform for delivering diverse therapeutic microorganisms.
Keywords:
controlled releaseengineered living materialsprobioticssustained releasezero-order release

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