Controlled release of microorganisms from engineered living materials.

Area of Science:

• Biomaterials Science
• Microbiology
• Drug Delivery

Background:

• Probiotics modulate the microbiome and immune response, offering therapeutic benefits for complex diseases.
• Effective probiotic therapy requires sustained persistence and colonization at the target site.
• Existing methods lack biomaterials for sustained release of metabolically active probiotics.

Purpose of the Study:

• To develop a novel biomaterial for sustained release of active probiotics.
• To demonstrate a generic mechanism for controlled probiotic delivery.
• To overcome limitations of repeated probiotic administration.

Main Methods:

• Encapsulating stiff probiotic microorganisms within less stiff hydrogels.
• Utilizing microbial proliferation to induce hydrogel fracture and release.
• Characterizing release kinetics and controlling delivery by matrix properties.

Main Results:

• Engineered living materials (ELMs) achieve zero-order release kinetics of probiotics.
• Small ELMs release >10^8 colony-forming units (CFUs) of E. coli within 2 hours, sustained for over 10 days.
• Probiotic release is controllable via initial cell loading and matrix mechanical properties.

Conclusions:

• A novel, generic mechanism for sustained probiotic release via hydrogel fracture has been demonstrated.
• This approach enables controlled delivery of diverse probiotic types (bacterial and fungal).
• The technology holds potential for treating a broad range of diseases requiring probiotic therapy.