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

Area of Science:

• Biomaterials Science
• Immunology
• Computational Biology

Background:

• Understanding foreign-body responses to biomaterials is crucial for implant design.
• Intercellular communication networks in the implant microenvironment remain poorly understood.

Purpose of the Study:

• To computationally reconstruct and analyze intercellular signaling networks in response to implanted biomaterials.
• To identify cell subsets and signaling pathways involved in biomaterial-specific responses.

Main Methods:

• Single-cell RNA sequencing of 42,156 cells from mouse models implanted with polycaprolactone or extracellular-matrix-derived scaffolds.
• Computational analysis of intercellular signaling networks based on predicted transcription-factor activation.
• Validation in an Il17ra knockout mouse model.

Main Results:

• Intercellular signaling networks form modules associated with specific cell subsets.
• Biomaterial responses are characterized by interactions between immune, fibroblast, and tissue-specific cell signaling modules.
• Identified novel cell subsets involved in biomaterial responses and validated interleukin-17 pathway involvement.

Conclusions:

• Single-cell atlases of cellular responses to biomaterials are essential for improved implant design.
• This approach provides a framework for understanding complex cellular interactions in response to implanted devices.