Substrate fiber alignment mediates tendon cell response to inflammatory signaling

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cell Biology

Background:

• Healthy tendons have aligned extracellular matrix (ECM), while disease leads to disorganization.
• Inflammation and immune cell-fibroblast crosstalk contribute to poor tendon healing.
• Current biomaterial scaffolds often produce scar-like tissue instead of aligned ECM.

Purpose of the Study:

• To investigate if disorganized tissue architecture predisposes tendon cells to degenerative ECM remodeling in a pro-inflammatory environment.
• To determine the effect of biomaterial scaffold fiber orientation on tendon fibroblast behavior and response to inflammation.

Main Methods:

• Human tendon fibroblasts (TFs) were cultured on electrospun polycaprolactone (PCL) mats with aligned or random fiber structures.
• TF morphology, phenotype, and matrix turnover markers were analyzed.
• TF responses to macrophage-derived signals and pro-inflammatory cytokines were assessed.

Main Results:

• Matrix topography significantly affected fibroblast morphology, phenotype, and matrix turnover.
• Pro-inflammatory conditions led to downregulated ECM synthesis and upregulated matrix-degrading enzymes in TFs.
• These degenerative changes were exacerbated on randomly oriented PCL substrates.

Conclusions:

• Highly aligned tendon cell scaffolds promote ECM synthesis and mitigate adverse fibroblast responses in an inflammatory milieu.
• Scaffold design, specifically fiber orientation, is critical for guiding tendon healing and preventing scar formation.
• This work informs the development of cell-instructive biomaterial therapies for improved tendon repair outcomes.