# Tendon Tissue Engineering Informed by Lysyl Oxidase Regulation of Embryonic Tendon Mechanical Properties

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2021 · $319,996

## Abstract

PROJECT SUMMARY
Musculoskeletal injuries are a leading cause of disability and medical costs in the United States. Approximately
half of these injuries involve tendons and ligaments. The lifelong dysfunction, pain, and increased risk of re-
injury due to poor healing have motivated our long-term goal to regenerate new tendon from stem cells to
restore function and quality of life. Typical stem cell-based approaches aim to promote quantity of extracellular
matrix (ECM) content, with the assumption that ECM quantity correlates with mechanical properties. However,
these approaches have yet to achieve functional tendons. This has led us to ask how tendon develops
naturally in the embryo to inform a mesenchymal stem cell (MSC)-based tendon regeneration approach.
 Our studies in the chick embryo recently showed that lysyl oxidase (LOX)-mediated crosslinking
correlates strongly with mechanical properties during tendon development, and that inhibition of LOX activity
reduces crosslinking and elastic modulus despite continued increases in matrix content. Furthermore, LOX
activity appears to be regulated by embryonic kicking (mechanical loading). Based on these exciting data, we
hypothesize LOX is a critical regulator of developing tendon mechanical properties, and that developmentally
informed manipulation of LOX activity can promote functional tendon regeneration with MSC. The hypothesis
will be tested with the following three specific aims: 1) determine LOX expression patterns and role in
embryonic tendon mechanical property development; 2) elucidate how mechanical loading regulates LOX
during embryonic tendon development; 3) develop approaches to enhance engineered MSC-construct
mechanical properties via LOX-mediated crosslinking.
 The proposed work is innovative because our approach focuses on restoring ECM quality, rather than
quantity, of the regenerating tendon matrix, and aims to inform this approach with embryonic development. Our
novel strategy combines the chick embryo model with tissue engineering and bioreactor loading systems to
investigate LOX and mechanical loading interactions in functional tendon development. Our long-term goal is
to design developmentally inspired LOX-targeted therapies utilizing MSC to improve tendon mechanical
properties.

## Key facts

- **NIH application ID:** 10471343
- **Project number:** 5R01AR072886-05
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Catherine K. Kuo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $319,996
- **Award type:** 5
- **Project period:** 2017-09-21 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471343

## Citation

> US National Institutes of Health, RePORTER application 10471343, Tendon Tissue Engineering Informed by Lysyl Oxidase Regulation of Embryonic Tendon Mechanical Properties (5R01AR072886-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10471343. Licensed CC0.

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