# Multiscale tendon damage and aberrant cellular responses in an in vivo model of tendinosis

> **NIH NIH R01** · UNIVERSITY OF DELAWARE · 2024 · $460,839

## Abstract

Project Summary
 Tendon overuse initiates mechanical damage that leads to chronic tendinosis (degeneration) and
tendinopathy (clinical presentation with pain), which are common and notoriously difficult to treat. Despite the
widely accepted role of loading in tendinosis, the structural, mechanical, and cellular mechanisms by which
loading leads to initiation and progressive damage in tendinosis remain unknown. We hypothesize that
overload causes micro-scale structural and mechanical damage, which alters load transmission to
cells, driving the multi-scale structural and molecular progression of tendinosis in a vicious cycle.
 To determine the mechanisms involved in tendinosis, a preclinical in vivo animal model of tendon
overuse and multiscale assessments of tendon structural and mechanical damage and interrogation of
cellular mechanotransduction and intracellular signaling mechanisms are all required. This is because
the physiological processes in tendinosis involve tissue-scale tendon loading that is transferred to the micro-,
nano-, and molecular-scale, where microstructural damage and cellular mechanotransduction signaling occurs.
Our team has recently established a model of tendinosis using rat synergist ablation (SynAb), where we
remove the Achilles tendon, which overloads the synergistic plantaris tendon without directly injuring it. Our
pilot data exhibit hallmark features of human tendinosis (increased area, collagen disorganization,
proteoglycan accumulation, collagen Type III production, and reduced tensile modulus).
 Our long-term goal is to enable interventions for tendon regeneration and rehabilitation to treat tendinopathy
and prevent its progression. The objective of this proposal is to determine the mechanisms responsible
for onset and progression of tendinosis in the SynAb model of tendon overuse in the following aims:
Aim 1: Assess the multiscale structural changes following the onset and progression of tendinosis.
Aim 2: Quantify the multiscale mechanical properties and damage following the onset and progression
of tendinosis.
Aim 3: Interrogate changes in tenocyte mechanoresponse and cytoskeleton during tendon overload.
This study will determine the mechanisms responsible for the multiscale damage in overuse tendinosis and
establish these in the context of key hallmarks of human tendinosis using a preclinical in vivo model.
Quantifying multiscale damage and cellular mechanisms by which loading leads to tendinosis is critical for
designing and evaluating interventions to prevent and treat tendinopathy.

## Key facts

- **NIH application ID:** 10891496
- **Project number:** 5R01AR080059-03
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** DAWN M ELLIOTT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $460,839
- **Award type:** 5
- **Project period:** 2022-08-22 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891496

## Citation

> US National Institutes of Health, RePORTER application 10891496, Multiscale tendon damage and aberrant cellular responses in an in vivo model of tendinosis (5R01AR080059-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10891496. Licensed CC0.

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