PhD Thesis Proposal: Afton Limberg

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Meeting ID: 940 7934 1413
Passcode: 436823

"The Effects of Hyperbaric Oxygen on Achilles Tendon Healing"

Abstract

Tendon injuries, particularly those affecting the Achilles tendon, present significant challenges in clinical rehabilitation due to the limited regenerative capacity of tendon tissue. Hyperbaric oxygen therapy (HBOT) has emerged as a promising adjunct therapy to established treatments for enhancing tissue repair by promoting cellular recovery and collagen remodeling. This dissertation investigates the effects of HBOT on tendon biology through a series of complementary models: in vitro, ex vivo, and in vivo, to comprehensively evaluate its therapeutic potential for tendon repair.

Chapter 2 explores an in vitro model where murine Achilles tenocytes are exposed to HBOT to assess cellular responses, including mitochondrial activity, cell viability, collagen deposition, and gene expression under both basal and inflammatory conditions. Preliminary findings demonstrate that HBOT significantly influences mitochondrial function and collagen production, suggesting its potential to modulate the cellular environment during tendon healing.

Building upon the in vitro findings, Chapter 3 extends the investigation to an ex vivo model using whole murine Achilles tendons cultured in a static environment. Tendons are subjected to injury and HBOT, and the outcomes are assessed at 24 hours, 72 hours, and 7 days. These assessments include histological analysis to evaluate protein expression and extracellular matrix deposition, gene expression analysis for tendon-specific and oxygen-responsive genes, quantitative polarized light imaging to examine collagen alignment, and biomechanical testing to evaluate tissue strength.

Finally, Chapter 4 examines the application of HBOT in an in vivo mouse model of Achilles tendon injury. The in vivo study assesses the therapeutic efficacy of HBOT in promoting tendon healing by evaluating tissue repair, collagen deposition, and mechanical function over time. Similar analyses to those performed in the ex vivo model will be conducted, allowing for direct comparison between the two studies. Together, these models provide a comprehensive evaluation of HBOT's effects on tendon biology, offering insights into its therapeutic mechanisms and potential clinical applications for tendon repair.

Thesis Committee

• Professor Douglas Van Citters (co-Chair)
• Professor Katherine Hixon (co-Chair)
• Dr. Jay Buckey Jr.
• Dr. Frances Faro
• Professor Spencer Lake (Washington University in Saint Louis)

Contact

For more information, contact Thayer Registrar at thayer.registrar@dartmouth.edu.