Team:SZPT-CHINA/Implementation
Implementation
Overview
Users
Envisioned usage
Benefits
Safety
Challenge
● Overview
Our goal is to develop an engineered live biotherapeutic to fight with
Pseudomonas aeruginosa infection and protect the burn wound simultaneously. We aim to use optogenetically engineered
Gluconacetobacter
hansenii to synthesize and release antipseudomonal drugs and produce a bacterial cellulose dressing on the burn wound surface to promote burn healing. Either function can be performed independently under
dual-light control.
To implement our project in the real world, we identified our users, designed different product formats, and built our engineering architecture for safety control through integrated human practices.
Figure 1. Project framework
● Users
Figure 2. Users
● Envisioned usage
Product formats and methods of use
We envisioned two different formats of our products for the engineered live biotherapeutic, that is bacterial emulsion and freeze-dried bacteria. The two product formats have different storage conditions
and shelf life to meet different user needs. (Please click Proof of Concept to see the protocols).
Figure 3. Proposed product formats
Methods of use for both products are shown in Figure 4 and Figure 5 respectively.
Figure 4. Method of use for bacterial emulsion
Figure 5. Method of use for freeze-dried bacteria
Usage scenarios
According to the size of the burn area, we designed two types of lighting device for patients. Through the interview with the firefighters, we learned that they wanted a portable appliance for burn treatment. So, we designed the portable lighting device for dual light control to be used with our products. This device is suitable for treatment of small area burns.
Figure 6. Portable light control device for small area burns.
In order to facilitate the treatment of large area burns, we designed an apparatus with an array of LEDs as shown in Figure 7.
Figure 7.The apparatus with an array of LEDs for treatment of large area burns
●Benefits
Figure 8. the two-in-one function of our product
Protect the burn wound to promote healing
The product can produce a bacterial cellulose dressing on the burn wound surface when irradiated with NIR light. This BC dressing has high mechanical strength, good biocompatibility,
maintains a moist
environment and act as a barrier to foreign microorganisms.
Kill P. aeruginosa in the burn wound
The product can produce a bacterial cellulose dressing on the burn wound surface when irradiated with NIR light.
●Safety
Risk of live biotherapeutic
In the case of our product usage on the burn wound, translocation of the G. hansenii across the skin barrier might be a safety concern. With respect to the relationship between translocation potential and pathogenicity, two
aspects should be addressed:
(1) the ability to cross skin barrier, and (2) the potential to induce a pathogenic reaction upon passage to the systemic circulation (inflammation or bacteria-mediated organ damage).
Human commensal bacteria on the skin might be capable of metabolizing the antipseudomonal drugs and/or drug metabolites affecting the pharmacokinetics of the drug, affecting the efficacy and toxicity assessment of drugs.
(1) the ability to cross skin barrier, and (2) the potential to induce a pathogenic reaction upon passage to the systemic circulation (inflammation or bacteria-mediated organ damage).
Human commensal bacteria on the skin might be capable of metabolizing the antipseudomonal drugs and/or drug metabolites affecting the pharmacokinetics of the drug, affecting the efficacy and toxicity assessment of drugs.
Risk of environmental release: safety module design
We designed a safety module that can trigger cell lysis under environmental blue light to reduce the risk of environmental release of our engineered bacteria. (Learn more Design)
Figure 9. Safety and drug release (cell lysis) module
●Challenge
Public acceptance
The public is concerned about the safety of live bacteria products, and our products may be questioned. Reducing the psychological burden of the public is important.
Application
It takes a long time for products to come into the market. Research and development → clinical trials → human trials → NDA declaration → clinical testing phase → listing