Design of a responsive barrier to prolong activity of probiotic bacteria over time
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- Probiotics and genetically modified commensal bacteria are promising therapeutic agents, but the inability to control their proliferation and activity over time limits their clinical exploitation. This master’s thesis aims at developing a self-regulated barrier system in which the probiotic Bacillus subtilis can drive its own controlled migration through a porous membrane by enzymatically degrading a gelatin-agarose composite hydrogel filling the membrane pores. A gelatin-agarose formulation, thermally stable at 37°C but still degradable by the gelatinase enzyme, was first identified and validated. Bacterial diffusion hrough the complete system, consisting of a track-etched PET membrane with pores filled with the gelatin-agarose gel and a gel layer on the inoculated side of the membrane, resulted in a reproducible delay of approximately 4 hours compared to a control with a bare membrane. This proof-of-concept supports the possibility that bacterial enzymatic activity could trigger barrier opening, paving the way for the design of self-regulated living delivery systems with controlled release kinetics.