Computational reconstruction of the signalling networks surrounding implanted biomaterials from single-cell transcriptomics

Nat Biomed Eng. 2021 Oct;5(10):1228-1238. doi: 10.1038/s41551-021-00770-5. Epub 2021 Aug 2.


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 collected 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 predictions 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-/- mouse model, we validated that predicted interleukin-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biocompatible Materials*
  • Extracellular Matrix
  • Foreign-Body Reaction*
  • Mice
  • Prostheses and Implants
  • Transcriptome


  • Biocompatible Materials