Michael Barbella, Managing Editor02.23.24
Nathaniel A. Dyment, Ph.D., has recieved 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 scar tissue development, 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 bone.ii 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 orthopedic surgery, Perelman School of Medicine at the 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:
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.
The Kappa Delta Sorority established the Kappa Delta Research Fellowship in Orthopaedics in 1947; it was the first award ever created to honor achievements in orthopedic research. The first annual award, a single stipend of $1,000, was made available to the American Academy of Orthopaedic Surgeons (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 orthopedic 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.
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, providing comprehensive education to help orthopedic surgeons and allied health professionals best treat patients. 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.
References
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. 7th 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. 1st 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.
Tendon and ligament disease and injuries affect more than 30% of adults in the United States,i and have poor healing outcomes due to scar tissue development, 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 bone.ii 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 orthopedic surgery, Perelman School of Medicine at the 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 regulationiv 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.
- 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.
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.
The Kappa Delta Sorority established the Kappa Delta Research Fellowship in Orthopaedics in 1947; it was the first award ever created to honor achievements in orthopedic research. The first annual award, a single stipend of $1,000, was made available to the American Academy of Orthopaedic Surgeons (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 orthopedic 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.
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, providing comprehensive education to help orthopedic surgeons and allied health professionals best treat patients. 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.
References
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. 7th 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. 1st 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.