First, our comprehensive in vivo study combining advanced animal model systems of immune-aging with scRNA seq represent a substantial step forward in unraveling the cellular self-organization in the complex and highly dynamics injured niche after bone fracture by providing detailed insights int spatial and temporal changes in immune and stromal cell compartments. Findings will lay the basis for developing immunomodulatory therapies for patients with impaired healing capacity due to dysregulated immune responses.
Furthermore, our integration of spatial transcriptomics across seven different organs has provided unprecedented insights into the dynamic gene expression programs that govern tissue repair. The identification of five distinct gene expression modules not only elucidates the molecular underpinnings of regeneration but also highlights critical differences between regenerative and fibrotic outcomes. From this analysis, three promising therapeutic targets have emerged, representing a major leap forward in our ability to modulate the healing process.
Another significant achievement is our novel MRI mapping technology developed for non-invasive characterization of ECM biophysical properties. This breakthrough method links quantitative MRI relaxation parameters to tissue elasticity, swelling, and stress relaxation, offering a new diagnostic tool for monitoring tissue alterations in regeneration and pathology. With pilot scans performed in clinical workflows on human subjects underscores its impact and translational potential. The study resulted in a publication in Nature Biomedical Engineering.
In vitro, our work with synthetic ECM-mimicking hydrogels has elucidated how mechanical cues, such as matrix viscoelasticity, guides macrophage polarization. This discovery is pivotal because it demonstrates a direct link between the mechanical properties of the tissue microenvironment and the immune response in a regenerating niche after injury, thereby opening new avenues for therapeutic intervention in bone healing and other regenerative processes.
Finally, the successful establishment of a longitudinal in vivo imaging system (LIMBostomy) marks a major milestone. This technology enables simultaneous monitoring of vessel formation and collagen deposition during the early phases of bone regeneration, thereby providing a powerful tool to assess the efficacy of pro-angiogenic and immunomodulatory therapies in real time.
