Spatial Transcriptomics in Mechanomics: New Horizons in Exploring the Mechanoregulation of Bone Regeneration

In over 100 years, the field of bone mechanobiology has sought experimental techniques to unravel the molecular mechanisms governing the phenomenon of mechanically-regulated bone (re)modelling. Each cell within a fracture site resides within different local micro-environments characterized by different levels of mechanical strain - thus, preserving the spatial location of each cell is critical in relating cellular responses to mechanical stimuli. Our spatial transcriptomics based “mechanomics” platform facilitates spatially-resolved analysis of the molecular profiles of cells with respect to their local in vivo mechanical environment by integrating time-lapsed in vivo micro-computed tomography, spatial transcriptomics, and micro-finite element analysis. We investigate the transcriptomic responses of cells as a function of the local strain magnitude by identifying the differential expression of genes in regions of high and low strain within a fracture site. Our platform thus has the potential to address fundamental open questions within the field and identify novel mechano-responsive targets to enhance bone regeneration.