# Defining the Role of Type III Collagen in Neonatal Tendon Development and Healing

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2024 · $48,974

## Abstract

Project Abstract
Tendons can withstand large forces due to a highly aligned, dense collagen matrix. However, their low
cellularity and relative inability to recruit reparative cells post-injury, as well as susceptibility to excessive
scarring, results in loss of tendon structure and mechanical function. Type I collagen (Col1) is the primary
collagen of healthy tendon and type III collagen (Col3) is a minor constituent that increases in response to
injury. Persistently increased Col3 contributes to persistent fibrovascular scarring and structural and functional
deficits in the healing tendon. In perinatal tendons, Col3 is increased, similar to the injured state, compared to
healthy mature tendons. Unlike the healing response, the process of neonatal tendon development yields a
structurally and functionally superior tendon with a highly aligned Col1-dense matrix. Moreover, neonatal
developing tendon demonstrates improved efficiency and quality of healing compared to healing mature
tendon. Understanding the role of Col3 in the developmental and healing processes of the neonatal tendon will
increase our ability to recapitulate tendon development with tissue engineering and improve tendon injury
treatment. Therefore, our overall objective is to delineate the contribution of Col3 to development and healing
in the neonatal tendon through modulation of matrix properties and cellular activity. Specifically, we will test the
hypothesis that Col3 is crucial for early neonatal development but contributes less to regulation of development
at later time points as relative Col3 in the tendon decreases. We also hypothesize that the neonatal tendon has
enhanced capacity for a robust proliferative response to tendon injury which creates a Col3-dense healing
matrix favorable for tendon progenitor migration and differentiation to ultimately deposit aligned, Col1 fibrils
which restore tendon structure and function. To test these hypotheses, we generated a novel, inducible Col3
deficient mouse (i.e. Col3a1F/F) to temporally control Col3 reduction. The study aims are: Aim 1: Define the
temporal dynamics of the regulatory function(s) of Col3 during phases of neonatal tendon development and
Aim 2: Define the regulatory function(s) of Col3 during phases of neonatal healing. Viscoelastic mechanical
testing, transmission electron microscopy, immunohistochemistry, gene expression, proteomics, and 11
integrin analyses will be used to assess the structural, mechanical, and compositional properties of tendons in
both aims. Insights gleaned from this work will be relevant to a variety of conditions that reduce Col3
expression including vascular Ehlers Danlos syndrome, aging, smoking and menopause and will highlight
therapeutic targets for enhancing tendon injury treatment. The proposed work will be carried out in a world-
class training environment at the University of Pennsylvania’s McKay Orthopaedic Research Laboratory. This
environment combined with an expert sponsorship tea...

## Key facts

- **NIH application ID:** 10827861
- **Project number:** 5F31AR082282-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Margaret Kathryn Tamburro
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2022-12-07 → 2025-12-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827861

## Citation

> US National Institutes of Health, RePORTER application 10827861, Defining the Role of Type III Collagen in Neonatal Tendon Development and Healing (5F31AR082282-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10827861. Licensed CC0.

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