Researchers have long known that bacteria could potentially be used to deliver therapeutic drugs inside the human body. However, safely and successfully carrying out such a feat in humans has been a challenge. But now, researchers from Harvard have made another step forward toward the goal of using microbes as medicine. Their recent study, published in Science, details a novel method for containing engineered bacteria to keep them from infecting their host while still successfully delivering potentially life-saving medications.
Using engineered bacteria for therapeutic purposes
Researchers have had success in engineering implantable bacteria that can sense infections and then release medications to kill other bacteria or cancer cells. These engineered bacteria must still be contained, however, to prevent dissemination and toxicity.
To do this, attempts have been made using hydrogels to encapsulate the engineered bacteria, but these often failed to prevent escape over time due to increasing pressure from expanding bacterial colonies or under physical stress from the body. Genetic containment strategies have also been attempted, but often fail due to evolutionary changes in the bacteria over time.
Yet, the idea of bacteria as living therapeutics is still attractive to scientists because of their ability to colonize a wide range of physiological environments, such as mucosa, infected sites, skin, inflamed tissues and tumors, and the ability to deliver therapeutics in response to specific biological signals, as opposed to waiting until symptoms become noticeable in a compromised person. Still, a long-term, biocompatible solution that keeps bacteria confined while allowing them to function as drug factories is crucial for these implantable living materials (ILM) to provide reliable, safe therapies.
Keeping bacteria contained with a stiffer, tougher scaffold
The researchers involved in the new study identified two main aspects of existing hydrogel scaffolds that needed improvement. They wrote, “We hypothesized that fulfilling two key criteria for a material enables robust and durable containment of therapeutic bacteria: (i) resistance to the internal forces generated by proliferating bacteria and (ii) mechanical toughness sufficient to withstand deformation from surrounding tissues.”
And so, the team engineered an implantable polyvinyl alcohol (PVA) hydrogel with optimized stiffness and toughness to keep expanding colonies from breaking through and to resist breakage under body movement. They then embedded engineered E. coli bacteria in protective microgels within it.
The team then tested out the new scaffold in various situations. They allowed the encapsulated bacteria to sit in a nutrient broth in the lab for six months, checking in on it frequently to see if any bacteria leaked out. But the scaffold held the bacteria for the entire six-month period.
They also evaluated fatigue resistance using cyclic crack growth testing, which tests how fast a flaw grows in a material under repeated loading. The PVA material showed a high fatigue threshold that indicated a 10-fold improvement over previous agarose-based materials. The new scaffold material also outperformed agarose in mechanical robustness testing and showed that the bacteria remained inside and functional under stress.
Promising results for infection detection and treatment
The new ILM material was then tested out as a local drug depot in a mouse model. The mice were implanted with a pin containing the ILM and then infected with a bacteria called Pseudomonas aeruginosa, which is common in implant surgeries and known for having an inherent resistance to many common classes of antibiotics. The bacteria in the scaffold were engineered to detect P. aeruginosa and release a drug to treat the infection.
The mice implanted with the new ILM material and engineered bacteria showed significantly reduced infection, compared to controls. Engineered bacteria inside the ILM were able to successfully detect infection signals and release the antimicrobial proteins to treat the infections in mice.
The team also performed testing on cancer cells in the lab, which showed successful drug delivery using the new materials. They write, “To evaluate platform versatility beyond antimicrobial therapy, we tested ILMs in a cancer-relevant context. Conditioned media from ILMs encapsulating Escherichia coli ClearColi (Ecc) engineered to express an inducible pore-forming toxin significantly reduced viability of CT26 cancer cells compared with GFP controls.”
These results represent a big step in safer microbe-based drug delivery, although long-term safety and immune responses in humans still need to be studied. Further studies will also be helpful for determining potential effects or efficacy of chronic use and broader disease applications.
Written for you by our author Krystal Kasal, edited by Lisa Lock, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive.
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Publication details
Tetsuhiro Harimoto et al, Implantable living materials autonomously deliver therapeutics using contained engineered bacteria, Science (2026). DOI: 10.1126/science.aec2071
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