Format

Send to

Choose Destination
  • Filters activated: Field: Title Word. Clear all
Acta Biomater. 2018 Apr 15;71:306-317. doi: 10.1016/j.actbio.2018.03.004. Epub 2018 Mar 10.

Substrate fiber alignment mediates tendon cell response to inflammatory signaling.

Author information

1
Department of Orthopedics, Balgrist Hospital, University of Zurich, Zurich, Switzerland; Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
2
Department of Orthopedics, Balgrist Hospital, University of Zurich, Zurich, Switzerland; Institute for Biomechanics, ETH Zurich, Zurich, Switzerland; Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.
3
Department of Orthopedics, Balgrist Hospital, University of Zurich, Zurich, Switzerland; Institute for Biomechanics, ETH Zurich, Zurich, Switzerland. Electronic address: jess.snedeker@hest.ethz.ch.

Abstract

Healthy tendon tissue features a highly aligned extracellular matrix that becomes disorganized with disease. Recent evidence suggests that inflammation coexists with early degenerative changes in tendon, and that crosstalk between immune-cells and tendon fibroblasts (TFs) can contribute to poor tissue healing. We hypothesized that a disorganized tissue architecture may predispose tendon cells to degenerative extracellular matrix remodeling pathways, particularly within a pro-inflammatory niche. This hypothesis was tested by analyzing human TFs cultured on electrospun polycaprolactone (PCL) mats with either highly aligned or randomly oriented fiber structures. We confirmed that fibroblast morphology, phenotype, and markers of matrix turnover could be significantly affected by matrix topography. More strikingly, the TF response to paracrine signals from polarized macrophages or by stimulation with pro-inflammatory cytokines featured significant downregulation of signaling related to extracellular synthesis, with significant concomitant upregulation of gene and protein expression of matrix degrading enzymes. Critically, this tendency towards degenerative re-regulation was exacerbated on randomly oriented PCL substrates. These novel findings indicate that highly aligned tendon cell scaffolds not only promote tendon matrix synthesis, but also play a previously unappreciated role in mitigating adverse resident fibroblast response within an inflammatory milieu.

STATEMENT OF SIGNIFICANCE:

Use of biomaterial scaffolds for tendon repair often results in tissue formation characteristic of scar tissue, rather than the highly aligned type-1 collagen matrix of healthy tendons. We hypothesized that non-optimal biomaterial surfaces may play a role in these outcomes, specifically randomly oriented biomaterial surfaces that unintentionally mimic structure of pathological tendon. We observed that disorganized scaffold surfaces do adversely affect early cell attachment and gene expression. We further identified that disorganized fiber surfaces can prime tendon cells toward pro-inflammatory signaling. These findings represent provocative evidence unstructured fiber surfaces may underlie inflammatory responses that drive aberrant collagen matrix turnover. This work could be highly relevant for the design of cell instructive biomaterial therapies that yield positive clinical outcomes.

KEYWORDS:

Fibrosis; Macrophage; Matrix topography; Nanofibers; Tendinopathy

PMID:
29530822
DOI:
10.1016/j.actbio.2018.03.004
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center