Tendons are essential tissues that transfer mechanical forces between muscles and bones. This allows movement of the body and increases stability. Collagen is the main component of tendon, and collagen is well-aligned with the tensile forces that tendons are subjected to during use. However, other components of tendon also aid in its function. Of these other components, elastic fibers are known to affect how tendons respond to mechanical forces. When elastic fibers in tendon are damaged or degraded, chronic pain or injuries can develop. However, it remains unclear how elastic fibers contribute to the mechanical properties of tendon and how they respond to repetitive use. This project will address this important gap in knowledge by investigating the role of elastic fibers in tendon under a broad range of conditions. Information gained from this research will advance understanding of how tendons function under healthy conditions. This may eventually lead to improved strategies to treat or replace tendons that have damaged or degraded elastic fibers to restore function and reduce the burden associated with these conditions. This project will also develop a workshop on novel 3D tissue imaging to broaden impact within local research communities as well as partner with a high school biomedical science program to provide unique educational opportunities to aspiring scientists/engineers.

The objective of this research is to define the role of elastic fibers in tendon mechanics. Elastic fibers are a structural constituent of the tendon extracellular matrix and are therefore necessary for its mechanical integrity. Despite the evidence demonstrating the importance of elastic fibers in maintaining healthy mechanical properties in tendon, the detailed contributions of elastic fibers in tendon mechanics are not yet understood. This research will determine how elastic fibers affect the mechanical function of tendon by comparing the base structure, composition, and mechanics of normal and elastin-null mouse tendons using an array of experiments including two-photon and transmission electron microscopy, biochemical assays, and mechanical testing. The role of elastic fibers in overuse-induced tendinopathy will be determined using fatigue testing and forced treadmill running using mice to induce damage, while testing of cultured tendon explants will inform potential effects of elastic fibers on mechanotransduction. In addition, enzymatic degradation of elastic fibers in tendon will be utilized to evaluate the distinct roles of elastic fibers within fascicles and within the interfascicular matrix. Conclusions from this work will advance understanding of composition-dependent mechanics in tendon and ultimately inform efforts to restore proper function in tendons with elastinopathic conditions or with degradation caused by overuse or age. This work is co-funded by the Biomechanics & Mechanobiology and the Physiological Mechanisms & Biomechanics programs.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Project Start
Project End
Budget Start
2021-02-01
Budget End
2024-01-31
Support Year
Fiscal Year
2020
Total Cost
$454,261
Indirect Cost
Name
Washington University
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63130