Potential strain-dependent mechanisms defining matrix alignment in healing tendons

Authored by Jeffrey W Holmes, William J Richardson, Brian Kegerreis, Stavros Thomopoulos

Date Published: 2018

DOI: 10.1007/s10237-018-1044-5

Sponsors: United States National Institutes of Health (NIH) United States National Science Foundation (NSF)

Platforms: No platforms listed

Model Documentation: Other Narrative Flow charts Mathematical description

Model Code URLs: Model code not found

Abstract

Tendon mechanical function after injury and healing is largely determined by its underlying collagen structure, which in turn is dependent on the degree of mechanical loading experienced during healing. Experimental studies have shown seemingly conflicting outcomes: although collagen content steadily increases with increasing loads, collagen alignment peaks at an intermediate load. Herein, we explored potential collagen remodeling mechanisms that could give rise to this structural divergence in response to strain. We adapted an established agent-based model of collagen remodeling in order to simulate various strain-dependent cell and collagen interactions that govern long-term collagen content and fiber alignment. Our simulation results show two collagen remodeling mechanisms that give rise to divergent collagen content and alignment in healing tendons: (1) strain-induced collagen fiber damage in concert with increased rates of deposition at higher strains, or (2) strain-dependent rates of enzymatic degradation. These model predictions identify critical future experiments needed to isolate each mechanism's specific contribution to the structure of healing tendons.

Tags

wound healing Orientation Collagen computational model growth Gene-expression Extracellular-matrix Load Mechanobiology Supraspinatus tendon Cardiac fibroblasts Tendon Collagen expression Patellar tendon Stretch