In Vivo Analysis of the Local and Systemic Host Tissue Response to Living Therapeutic Materials in Mice

Leading PI: Matthias Laschke (Saarland University)

During the initial funding phase of the LSC LifeMat implantable living therapeutic materials (LTMs) using Pluronic and PVA hydrogels, which were successfully processed into multilayer thin films that could contain bacteria without leakage for extended periods. These hydrogels were proven non-toxic in vitro, and bioluminescent bacteria were engineered for long-term monitoring. However, the initial bacterial strains produced insufficient bioluminescence for reliable vivo imaging. To address this, new strains like Lactobacillus plantarum were developed, yielding a 100-fold increase in signal strength, which proved adequate for imaging in mouse cadavers.

Building on these results, the follow-up project aims to evaluate the in vivo biocompatibility and safety of these bacterial-loaded hydrogels in a chronic mouse model, with regulatory approval already secured. The research will focus on monitoring the implants over eight weeks using ultrasound and bioluminescence imaging, followed by histological and immunohistochemical analysis to assess vascularization, immune response, and tissue integration, along with systemic cytokine profiling. The work plan includes testing advanced LTMs from all LSC partners with varied designs and therapeutic functions.