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Developing a Single-Cell Spatial Transcriptomics Workflow for In Vivo Evaluation of Implanted Biomaterials.

Alex H P Chan1, Yunfei Hu1, Billie Pardavi1

  • 1School of Medical Sciences, Faculty of Health and Medicine, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
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Summary
This summary is machine-generated.

Spatial transcriptomics reveals distinct cellular responses to biomaterials, uncovering immune cell recruitment and fibrosis dynamics not seen with histology. This approach aids in designing improved biomaterials by understanding in vivo cellular mechanisms.

Keywords:
bioengineeringbiomaterialsin vivo evaluationpolycaprolactonespatial transcriptomics

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Area of Science:

  • Biomaterials Science
  • Cellular Biology
  • Bioinformatics

Background:

  • Histology is standard for in vivo biomaterial evaluation but lacks cellular mechanism insight.
  • Transcriptomics offers gene activity data but is underutilized in biomaterial assessment.
  • Spatial transcriptomics enables high-resolution gene expression mapping within tissues.

Purpose of the Study:

  • To develop a bioinformatics workflow for analyzing in vivo biomaterial responses using spatial transcriptomics on the Xenium platform.
  • To investigate the cellular and molecular mechanisms of tissue remodeling around implanted biomaterials.
  • To demonstrate the utility of spatial transcriptomics in uncovering cellular dynamics missed by traditional methods.

Main Methods:

  • Development of a bioinformatics workflow for Xenium spatial transcriptomics data analysis.
  • Evaluation of electrospun polycaprolactone (PCL) scaffolds implanted subcutaneously in mice.
  • Spatial analysis of gene expression to identify distinct cell subpopulations and their interactions.

Main Results:

  • Identification of spatially distinct macrophage and fibroblast subpopulations with unique gene expression profiles around PCL scaffolds.
  • Observed shared phenotypic features and spatial orientation between co-localized macrophages and fibroblasts from scaffold core to surface.
  • Linked spatial transitions to functional roles: immune cell recruitment within the scaffold and fibrosis at the surface.

Conclusions:

  • Spatial transcriptomics provides unprecedented insight into the cellular dynamics of biomaterial-tissue interactions.
  • The developed workflow enables detailed analysis of in vivo biomaterial responses.
  • This approach facilitates a more biologically informed design of next-generation biomaterials.