Project Details
Projekt
ProbioGel as Adaptive Living Skin and Wound Therapeutics
Subject Area
Biomaterials
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 541302265
ProbioGel is targeted to create engineered living materials (ELMs) as antibiotic-free skin therapeutics by combining engineered microgels and living probiotic bacteria (PB) in a synergistic way. To achieve this, we develop fundamental design concepts and rules to fabricate an adaptive ELM as “skin healing living scaffold / gel patch” containing bacteriocin-producing, skin pathogens controlling probiotic bacteria (PB) and functional microgel-based 3D macroporous scaffolds (MAPs), mutually influencing each other. In ProbioGel, we will replace the nonwoven, dried and enclosed between two membranes, of our established skin plaster ‘ProbioPad’ by a MAP to better regulate the proliferation of the PB by enhancing cell-cell interaction and availability of nutrients via diffusion. The non-living MAP will be modified with bacteria-adhesive sites and thus be shaped by the living PB via bio-interlinking. Moreover, the MAP will be modified to steer the antimicrobial function of the PB, e.g. via elevating production and triggered, on-demand booster release of inductive molecules. Design parameters for the microgel rods, produced by in-mold polymerization or microfluidics, like dimensions, aspect ratio, stiffness, reactivity, biomodification, and responsiveness to external signals, will be systematically varied. We will investigate how these parameters affect the dynamic nature of the scaffold, growth of bacteria, production, diffusion, and release of bacteriocins, antimicrobial functionality, and upscaling of the resulting ProbioGel-ELM. Moreover, we will evolve a biosafety strategy to strictly confine PB survival to the MAPs. Initially, the developed interactive and responsive rod-shaped microgels will be injected with PB to form a MAP scaffold inside the commercial outer membrane encasing of ProbioPad to ensure antimicrobial efficacy, built-in safety, and facilitating clinical translation. Secondly, we aim to replace the solid membrane by a softer, mechanically flexible hydrogel film containment with a composition and mesh size to restrict PB escape. The antimicrobial efficacy of the entire device, after combining with the microgels and PB inside, will be tested against a panel of pathogenic microorganisms using different antagonism tests on agar plates and eventually with an ex vivo skin infection model. Pivotal is the release of therapeutic molecules after MAP hydration via wound contact, with a booster mechanism via sensing of a signal molecule coming from severely infected wounds. This leads to a cascading adaptation of the living PB inside the non-living MAP and a triggered, increased release of therapeutics when needed from our ProbioGel_ELM. The microgels –potentially rendered responsive to triggers and for insertion into bioinks for 3D printing– can be provided to other researchers in the SPP. Moreover, adaptive linkers and biocontainment tools can be shared.
DFG Programme
Priority Programmes
Co-Investigator
Professor Dr. Rudolf Lütticken
