Predicting the safety and biocompatibility potential of bacterial hydrogels

• Applicant: Dr. Sara Trujillo Munoz, Ph.D.
• Subject Area: Biomaterials ; Cell Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 520576220

Living wearable devices have potential in biomedical applications. They are made of a material component and a living component. The living component is usually a microorganism that can be genetically modified to act as a sensor to different stimuli. The material is normally a hydrogel that allows the encapsulation of the living component and allows diffusion of nutrients and waste. The challenge of the use of living materials in patients comes from their interactions with the patient’s cells. The presence of a genetically modified living component in the material arises questions of safety, as these organisms are viable and functional. These microorganisms have the capability to interact with the natural flora of the patient. The living component can proliferate, and daughter cells can acquire undesired mutations. In addition, as the living component is functional it can secrete potentially harmful by-products of their own metabolism. On the other hand, the patient’s cells are prepared to detect and respond against external particles that could be regarded as foreign (like pathogens). Therefore, biocompatibility of the living materials and the immune response they may trigger need to be addressed for as long as the living material is functional and in contact with the patient. This project aims to systematically approach concerns on safety and biocompatibility of these living materials, generating specific assays in vitro to predict the probability of these devices to cause any unwanted side effects to the patient. The project is divided into 4 objectives: the first one aims to determine if the living material is secreting any of the major pathogen-associated molecules that could trigger an immune response. The second objective aims to determine the probability that a genetically modified bacterium of the living material could transfer unwanted genetic information to a resident bacterium of the patient. The third objective aims to determine the biocompatibility of the living material with mammalian cells and the fourth objective aims to assess toxicity of the living material in a complex environment such as the chick chorioallantoic membrane, which is an external epithelial tissue of the chick embryo. Future work will include the validation of these safety and biocompatibility concerns in more complex scenarios with the appropriate in vivo models.

• DFG Programme: Research Grants