Nathaniel A. Dyment, PhD, Presented With 2024 Kappa Delta Young Investigator Award for Research on Formation, Maintenance and Repair of Tendons and Ligaments

ROSEMONT, Ill., Feb. 2, 2024 /PRNewswire/ — Nathaniel A. Dyment, PhD, was named the recipient of the 2024 Kappa Delta Young Investigator Award for his findings on biophysical and biochemical cues that direct the growth and development, homeostasis and repair of tendons and ligaments. The award recognizes outstanding clinical research related to musculoskeletal disease or injury by investigators under 40 years old.

Tendon and ligament disease and injuries affect more than 30% of adults in the United States,ⁱ and have poor healing outcomes due to the development of scar tissue, which often leads to retears. Tendon disease and injuries typically occur in two areas of the tendon—the tendon midsubstance (the middle level of the tendon) and the enthesis (the attachment site of tendon to boneⁱⁱ). Unfortunately, clinicians and researchers lack biological benchmarks to assess the repairs of these tissues, hampering the development of new therapies.

“We don’t have specific markers that delineate between immature and mature tendon cells and don’t fully understand the biological and mechanical inputs that control tendon cell behavior,” said Dr. Dyment, assistant professor of orthopaedic surgery, Perelman School of Medicine, University of Pennsylvania. “Therefore, the development of treatments to successfully repair or regenerate tendons is very difficult. Often, a tendon tears near the bone at the enthesis and can frequently be a chronic tear. The degeneration that is happening in tendons can take decades to develop, making successful treatment of these injuries a big challenge. One strategy is to understand the disease process better so we can try to intervene earlier.”

Key Findings

Using mechanobiology, which studies how mechanical factors affect cell behavior,ⁱⁱⁱ Dr. Dyment and his colleagues explored tendon tensional homeostasis, which is critical to maintaining tendon tissue properties. Tensional homeostasis is the result of extrinsic (applied) loads, such as those from activities of daily living, and intrinsic (internal) loads, often generated by structural proteins inside the cell. The researchers explored how mechanical forces affect tendons during the various stages of embryonic development, postnatal growth and homeostasis. The major findings included:

Muscle contraction is critical to postnatal growth of the Achilles tendon and can impair growth if reduced.
Non-muscle myosin II motor proteins, which contribute to cellular organization and regulation^iv and help drive cell tension, are required to maintain the tendon matrix into adulthood.
The loss of cellular tension in adult tendons leads to a robust catabolic response, regulated by the mechano-responsive Yap/Taz signaling pathway, which plays a role in cell growth and proliferation.

When torn tendons are sutured back to the bone, these repairs often lead to the formation of scar tissue and don’t produce an organized enthesis structure at the attachment site. The research team set out to understand the specific cell populations that participate in the healing response, which can help promote enthesis formation following an injury. Dr. Dyment and his team used the anterior cruciate ligament reconstruction (ACLR) surgical model as a test platform to manipulate specific cell populations during the tendon-to-bone integration process that occurs between the tendon graft and adjacent bone following surgery. Their findings showed:

At four weeks post-surgery, zonal tendon-to-bone attachments were seen in the bone tunnels. While more disorganized, the zonal attachments shared common features with native entheses.
Activating the Hedgehog (Hh) signaling pathway—a key regulator of enthesis formation during growth and development—increased the production of tendon-to-bone attachments following ACLR. This indicates that the Hh pathway could be a therapeutic target to improve tendon-to-bone repair.
Dr. Dyment’s lab, in collaboration with his colleagues Drs. Andrew Kuntz and Robert Mauck, developed scaffold delivery systems to localize delivery of Hh signaling drugs to the bone tunnels.

“Using developmental studies–how the tissue originally forms–we determined the elements that are absolutely critical to the establishment of this tissue,” said Dr. Dyment. “The Hedgehog pathway was specifically expressed by cells where the tendon inserts into bone that produce fibrocartilage in this area. The pathway is also a potent regulator of fibrocartilage production in the enthesis and, excitingly, we found that it appears to have a similar role in tendon-to-bone integration in adults.”

Several of Dr. Dyment’s mentors and colleagues were instrumental to this research, including, but not limited to, David Butler, David Rowe, Louis Soslowsky, Robert Mauck, Andrew Kuntz, Joel Boerckel, Lin Han, Eiki Koyama, Catherine Bautista, Mary Kate Evans, Natalie Fogarty, Keitaro Fujino, Yusuke Hagiwara, Xi Jiang, Talayah Johnson, Dakota Jones, Tim Kamalitdinov, Jonathan Marcelin, Rashad Madi and Tonia Tsinman.

To read more about the award, please click here.

About the Kappa Delta Awards

In 1947, at its golden anniversary, the Kappa Delta Sorority established the Kappa Delta Research Fellowship in Orthopaedics, the first award ever created to honor achievements in the field of orthopaedic research. The first annual award, a single stipend of $1,000, was made available to the AAOS in 1949 and presented at the AAOS meeting in 1950. The Kappa Delta Awards have been presented by the AAOS to persons who have performed research in orthopaedic surgery that is of high significance and impact.

The sorority has since added two more awards and increased the award amounts to $20,000 each. Two awards are named for the sorority national past presidents who were instrumental in the creation of the awards: Elizabeth Winston Lanier and Ann Doner Vaughn. The third is known as the Young Investigator Award. For more information about the manuscript submission process, please visit aaos.org/kappadelta. Learn more about the Kappa Delta Foundation, here.

About the AAOS

With more than 39,000 members, the American Academy of Orthopaedic Surgeons is the world’s largest medical association of musculoskeletal specialists. The AAOS is the trusted leader in advancing musculoskeletal health. It provides the highest quality, most comprehensive education to help orthopaedic surgeons and allied health professionals at every career level to best treat patients in their daily practices. The AAOS is the source for information on bone and joint conditions, treatments and related musculoskeletal health care issues; and it leads the health care discussion on advancing quality.

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Disclosure

Funding and Conflicts of Interest

Dr. Dyment has no conflicts of interests.

Funding Sources:

NIH/NIAMS Grants

K99/R00 (AR067283)

R01 (AR076381)

R21 (AR078429)

P50 (AR080581)

R01 (AR075418)

F31 (AR079840)

T32 (AR007132)

Additional Funding/Awards

National Science Foundation

Penn Perelman School of Medicine McCabe Fund Pilot Award

Penn Center for Musculoskeletal Disorders (PCMD) Pilot award

University Research Foundation at University of Pennsylvania

ⁱ McCormick A, Charlton J, Fleming D. Assessing health needs in primary care. Morbidity study from general practice provides another source of information. BMJ. 1995;310:1534.

ⁱⁱ Petty RE, Laxer RM, Lindsley CB, Wedderburn L. Textbook of Pediatric Rheumatology. 7^th ed. Philadelphia, PA. Elsevier Health Sciences. 2015.

ⁱⁱⁱ Gomes ME, Reis RL, Rodrigues, MT. Tendon Regeneration: Understanding Tissue Physiology and Development to Engineer Functional Substitutes. 1^st ed. Academic Press. 2015.

^iv Newell-Litwa KA, Horwitz R, Lamers ML. Non-muscle myosin II in disease: mechanisms and therapeutic opportunities. Dis Model Mech. 2015 Dec;8(12):1495-515.