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Human Tendon-on-a-Chip for Modeling the Myofibroblast Microenvironment in Peritendinous Fibrosis
Raquel E Ajalik1,2, Isabelle Linares1,2, Rahul G Alenchery1,2
1Center for Musculoskeletal Research, Department of Orthopaedics, University of Rochester, Rochester, NY, 14642, USA.
Advanced Healthcare Materials
|November 15, 2024
Summary
A new human tendon-on-a-chip model replicates fibrotic disease features, showing promise for testing therapies. This innovative model aids in understanding myofibroblast interactions and developing treatments for fibrotic conditions.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Tissue Engineering
Background:
- Fibrotic diseases, particularly peritendinous adhesions, lack effective biological therapies.
- Understanding the myofibroblast microenvironment is crucial for developing targeted treatments.
- Current models do not fully capture the complex cellular and paracrine interactions in fibrotic conditions.
Purpose of the Study:
- To develop and validate a novel human tendon-on-a-chip (hToC) model.
- To investigate multicellular crosstalk in the context of fibrotic peritendinous adhesions.
- To establish a platform for testing therapeutic interventions for fibrosis.
Main Methods:
- Development of a microfluidic device (hToC) integrating vascular and tissue hydrogel components.
- Co-culture of endothelial cells, monocytes, tendon cells, and macrophages within the hToC.
- Analysis of inflammatory and fibrotic phenotypes, including gene expression and cytokine secretion.
- Assessment of therapeutic efficacy using rapamycin treatment.
Main Results:
- The hToC successfully replicated key in vivo fibrotic and inflammatory phenotypes.
- Activated mTOR signaling, vascular inflammation, and myofibroblast-induced tissue contraction were observed.
- Significant overlap in enriched pathways was found between the hToC and human tenolysis samples.
- Rapamycin treatment demonstrated a suppression of vascular inflammation and fibrotic markers.
Conclusions:
- The hToC serves as a valuable in vitro tool for studying multicellular crosstalk in fibrosis.
- This model provides a platform for preclinical testing of therapeutics targeting fibrotic diseases.
- The findings support the development of novel therapies for conditions like peritendinous adhesions.
