A single-cell atlas of the microenvironment of implanted biomaterials and computational analysis of the transcriptional signalling networks [bulk RNA-seq]

The understanding of the foreign-body responses to implanted biomaterials would benefit from the reconstruction of intracellular and intercellular signalling networks in the microenvironment surrounding the implant. Here, by leveraging single-cell RNA-sequencing data from 42,156 cells harvested from the site of implantation of either polycaprolactone or an extracellular-matrix-derived scaffold in a mouse model of volumetric muscle loss, we report a computational analysis of intercellular-signalling networks reconstructed from data of transcription-factor activation. We found that intercellular signalling networks can be clustered into modules associated with specific cell subsets, and that biomaterial-specific responses can be characterized by interactions between signalling modules for immune, fibroblast and tissue-specific cells. In a Il17ra–/¬– knockout mouse model, we validated that predicted IL-17-linked transcriptional targets led to concomitant changes in gene expression. Moreover, we identified cell subsets that had not been implicated in the responses to implanted biomaterials. Single-cell atlases of the cellular responses to implanted biomaterials will facilitate the design of implantable biomaterials and the understanding of the ensuing cellular responses. Triplicate of animals given volumetric muscle loss in wild type C57BL/6 or IL17ra knockout animals.