Transcriptomic analysis of the human macrophage response to 13 polymeric materials.

Fibrosis around implanted medical devices is a common complication that affects their functionality and long-term success. However, reliable in vitro assays to predict this fibrotic response are currently lacking, limiting the ability to generate human-relevant preclinical data. In this study, we used THP-1-derived human macrophages to evaluate cellular responses relevant for in vitro prediction of fibrosis across six groups of polymeric materials with varying surface texture, chemical composition, stiffness, or porosity. Cell death, metabolism, cytokine secretion, and transcriptomic profiles were assessed and compared to previously characterised in vivo fibrosis outcomes. All assays were able to distinguish between high and low fibrosis-inducing materials within one or more material groups. Importantly, different biomaterials differentially modulated the various readouts, with some assays showing greater sensitivity to specific material properties than others. Conditional logistic regression modelling identified increased secretion of TNF-α at the 24 hour timepoint and IL-1RA at the 72 hour timepoint as being associated with higher fibrosis levels. Transcriptomic profiling revealed distinct, material-specific gene expression changes, alongside shared responses for certain material subsets, indicating convergent macrophage activation pathways. Notably, several high fibrosis materials showed differential regulation of genes involved in oxidative stress pathways. Additionally, gene set enrichment analysis revealed an upregulation of lipid and cholesterol metabolism pathways in several high fibrosis materials. Altogether, these findings demonstrate the potential of multi-assay macrophage profiling for in vitro biomaterial screening and suggest candidate markers for future assay development.