# Studying Mechanotransduction in Late Embryonic Development to Inform Tendon Tissue Engineering

> **NIH NIH R21** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $157,973

## Abstract

Project Summary/Abstract
Tendon and ligament injuries are a common cause of disability and pain. In many cases, the injured tissue cannot
be repaired directly and must be replaced with a graft material. Ideally, a tissue engineered biomaterial could be
used for this purpose; however, no tissue engineered construct has been successfully used to reconstruct human
tendon or ligament ruptures. A primary reason for the failure in producing successful tendon replacements is that
most tissue engineering approaches do not replicate normal tendon development. Scaffold-free techniques
based on cellular self-assembly are able to generate tissues that that match the structure and mechanics of early
embryonic tendon. However, they are unable to undergo a critical phase in late tendon development where the
collagen fibrils elongate and fuse together generating a substantially stiffer and stronger material. One reason
for this is that the constructs lacked the mechanical stimulation normally provided in vivo by muscles. In fact,
chick embryo muscle activity peaks during late tendon development and this muscle activity is responsible for
increasing the modulus of embryonic tendons. Nevertheless, while mechanical loading of constructs does
improve tissue mechanics, they still fail to match the order-of-magnitude increase in mechanical properties
observed in embryonic chick tendons. A critical barrier is the lack of knowledge regarding the
mechanotransduction mechanisms that determine the cellular response to mechanical stimulation and drive late
tendon development. Understanding how tendon cells respond to mechanical stimuli due to not only muscle
loading but also the local changes in tissue structure and mechanics that occur during development is necessary
to develop biomaterials that can successfully replicate tendon function. Therefore, the objective of this project is
to identify the mechanotransduction mechanisms that mediate the multiscale changes in tissue structure and
mechanics observed during late tendon development. Specifically, this project will (1) identify the multiscale
structural and mechanical changes that occur during late tendon development and (2) determine the
mechanotransduction mechanisms driving these changes. The overall hypothesis is that cells sense mechanical
stimuli through a combination of cell-cell and cell-matrix interactions and that these mechanotransduction events
are essential for driving proper tendon development. This will be evaluated by inhibiting embryonic muscle
activity and perturbing mechanotransduction signaling in embryonic tendons via site-specific gene knockout
during ex ovo culture of chicken embryos. The effects of these manipulations on tendon structure and mechanics
will be determined by a novel combination of multiscale mechanical testing, computational modeling, and
ultrastructural imaging. This work is the first investigation of the mechanotransduction mechanisms driving the
structural and mechanical changes...

## Key facts

- **NIH application ID:** 9969347
- **Project number:** 5R21AR075941-02
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Spencer Szczesny
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $157,973
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969347

## Citation

> US National Institutes of Health, RePORTER application 9969347, Studying Mechanotransduction in Late Embryonic Development to Inform Tendon Tissue Engineering (5R21AR075941-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9969347. Licensed CC0.

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