Targeting Cell Contractile Forces: A Novel Minimally Invasive Treatment Strategy for Fibrosis

Keerthi Atluri; Sathivel Chinnathambi; Alyssa Mendenhall; James A Martin; Edward A Sander; Aliasger K Salem

doi:10.1007/s10439-020-02497-x

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Targeting Cell Contractile Forces: A Novel Minimally Invasive Treatment Strategy for Fibrosis

Journal article

Peer reviewed

Targeting Cell Contractile Forces: A Novel Minimally Invasive Treatment Strategy for Fibrosis

Keerthi Atluri, Sathivel Chinnathambi, Alyssa Mendenhall, James A Martin, Edward A Sander and Aliasger K Salem

Annals of biomedical engineering, Vol.48(6), pp.1850-1862

06/2020

DOI: 10.1007/s10439-020-02497-x

PMCID: PMC7286797

PMID: 32236751

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https://www.ncbi.nlm.nih.gov/pmc/articles/7286797View

Open Access

Abstract

Fibrosis is a complication of tendon injury where excessive scar tissue accumulates in and around the injured tissue, leading to painful and restricted joint motion. Unfortunately, fibrosis tends to recur after surgery, creating a need for alternative approaches to disrupt scar tissue. We posited a strategy founded on mechanobiological principles that collagen under tension generated by fibroblasts is resistant to degradation by collagenases. In this study, we tested the hypothesis that blebbistatin, a drug that inhibits cellular contractile forces, would increase the susceptibility of scar tissue to collagenase degradation. Decellularized tendon scaffolds (DTS) were treated with bacterial collagenase with or without external or cell-mediated internal tension. External tension producing strains of 2-4% significantly reduced collagen degradation compared with non-tensioned controls. Internal tension exerted by human fibroblasts seeded on DTS significantly reduced the area of the scaffolds compared to acellular controls and inhibited collagen degradation compared to free-floating DTS. Treatment of cell-seeded DTS with 50 mM blebbistatin restored susceptibility to collagenase degradation, which was significantly greater than in untreated controls (p < 0.01). These findings suggest that therapies combining collagenases with drugs that reduce cell force generation should be considered in cases of tendon fibrosis that do not respond to physiotherapy.

Collagen - metabolism

Collagenases - pharmacology

Fibroblasts - physiology

Fibrosis

Heterocyclic Compounds, 4 or More Rings - pharmacology

Humans

Stress, Mechanical

Tendons - drug effects

Tendons - pathology

Tissue Scaffolds

Details

Title: Subtitle: Targeting Cell Contractile Forces: A Novel Minimally Invasive Treatment Strategy for Fibrosis
Creators: Keerthi Atluri - University of Iowa
Sathivel Chinnathambi - University of Iowa
Alyssa Mendenhall - University of Iowa
James A Martin - University of Iowa
Edward A Sander - University of Iowa
Aliasger K Salem - University of Iowa
Resource Type: Journal article
Publication Details: Annals of biomedical engineering, Vol.48(6), pp.1850-1862
DOI: 10.1007/s10439-020-02497-x
PMID: 32236751
PMCID: PMC7286797
NLM abbreviation: Ann Biomed Eng
ISSN: 0090-6964
eISSN: 1573-9686
Grant note: P30 ES005605 / NIEHS NIH HHS R21 AR075137 / NIAMS NIH HHS W81XWH-14-1- 0327 / U.S. Department of Defense P30 CA086862 / NCI NIH HHS
Language: English
Date published: 06/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9984185373302771

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