Project Details
Projekt
Living Therapeutic Materials with long term, sonoresponsive and mechanoadaptive function
Subject Area
Polymer Materials
Synthesis and Properties of Functional Materials
Synthesis and Properties of Functional Materials
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 541300194
This proposal deals with the development of engineered living therapeutic materials (ELTMs) that consist of a hydrogel matrix wherein microbial biofactories are incorporated, which produce and release therapeutic agents. A particular focus is to render these ELTMs responsive to force, which allows to control these systems by ultrasound as an external trigger with clinical relevance and to achieve adaptive architectures where the host matrix and bacterial guests interact autonomously to control their function. In the first part of the proposal, our goal is to construct and characterize various synthetic systems, including hydrogels, microgels, microdroplets, and combinations thereof with in-built mechano- and sonoresponsive units exploiting well-defined covalent and non-covalent interactions as mechanophores. The cleavage of the disulphide- and thrombin/hirudin mechanophores within the polymer network will result in the loosening of the matrices upon application of mechanical force and ultrasound and is expected to expose the encapsulated biofactories to a new mechanical microenvironment, thereby influencing their growth and subsequent release of metabolites or therapeutics. This approach allows the manipulation of the living components through controlled engineering of the non-living matrices. In the second part of the proposal, we envision developing cascaded systems in which ultrasound exposure and the resulting forces trigger the release of small molecules. The released molecule then instructs bacterial function with the help of riboswitches encoded within the bacteria. Further, we aim at advancing the functionality of synthetic materials with living matter. To realize this, matrices with a shear modulus of 10-20 kPa will be employed to host bacteria. The stress exerted by the growing bacteria colonies on the polymer network (usually ~ 10 kPa) is anticipated to induce the release of incorporated signaling molecules, which in turn control the bacteria’s behavior with regard to their cell population and the production and release of bioactives. Thus, this proposal aims at exploiting fundamental concepts of mechanobiology and mechanochemistry to build triggerable systems that eventually enable the design of adaptive ELTMs.
DFG Programme
Priority Programmes
