Cutting-edge bioengineering for musculoskeletal regeneration the focus of research paper

Co-authored by Knight Campus researchers, special edition review paper appears in the journal Science Translational Medicine

Musculoskeletal injuries and disorders are the leading cause of physical disability worldwide, affecting an estimated 1.7 billion people. A new review paper co-authored by researchers in the Guldberg Lab at the Phil and Penny Knight Campus for Accelerating Scientific Impact provides an overview of the latest technological advances targeting musculoskeletal disorders, including recent efforts in translating state-of-the-art bioengineering approaches to therapies for musculoskeletal regeneration.

Alastair Khodabukus, a research scientist at Duke University, is the lead author on the paper, “Translating musculoskeletal bioengineering into tissue regeneration therapies,” which appears in the Oct. 12 edition of the journal Science Translational Medicine.

"It’s such an exciting time because the convergence of the latest bioengineering technologies with materials science, biology, and data science is now enabling advancement of therapeutic options like never before," said Robert Guldberg, a co-author on the paper and vice president and Robert and Leona DeArmond Executive Director of the Knight Campus. "These advances offer hope to effectively treat previously uncurable musculoskeletal problems such as osteoarthritis that cause so much unrelieved suffering."

High-resolution radiograph images of bones after fracture
High-resolution radiograph images of bones after fracture — non-union (top),  healing (bottom) — from a study on segmental defects.

Translating musculoskeletal research into real applications is a particularly broad topic, especially given the many different tissue types it includes, said Tyler Guyer, a third year Ph.D. student in the Guldberg Lab and a co-author on the paper. Musculoskeletal tissues are an interconnected system of skeletal muscle, tendon, bone, ligament, and cartilage that function collectively to provide structural support, stability, form and locomotion.

“The paper provides an overview of the types of research out there, what sorts of therapeutics are currently being developed, and the modern scope of the field,” Guyer said

Three separate labs, each with their individual areas of musculoskeletal expertise, contributed to the paper. The Bursac Lab at Duke University focused primarily on skeletal muscles, the Stevens Group at Imperial College London concentrated largely on cartilage and the Guldberg Lab in the Knight Campus dedicated most of its attention to bone regeneration.

Musculoskeletal disorders can also range widely in terms of their severity. They can arise from traumatic injury, aging, autoimmune disease, or genetic mutations, the researchers write in the paper’s introduction. Less severe disorders are treated with physical rehabilitation and pharmaceuticals, while severe defects require surgical interventions, including tissue grafting or the implantation of orthopedic devices.

In the paper, the researchers first discuss the self-repair capacity of musculoskeletal tissues and describe the causes of musculoskeletal dysfunction and the state of patient care. They then offer a review of the development of novel biomaterial, immunomodulatory, cellular, and gene therapies to treat musculoskeletal disorders. And finally, they consider recent regulatory changes and future areas of technological progress that could serve to accelerate translation of new therapies to clinical practice.

One of the challenges in writing the paper was in choosing what to include, Guyer said. He and other researchers reviewed far more therapeutic methods than they incorporated into the final version. There was also overlap in therapeutic approaches across the different tissue types and distinctions in how therapies can be applied to different tissues to be considered.

The researchers conclude that a number of factors, including new platforms for in-vitro models, new technologies in cellular therapy and advances in biomaterial design, immunomodulation and machine learning are all helping to pave the way for the next-generation of multi-component bioengineering therapies. The first approvals of these new therapies over the past decade and the development of more streamlined regulations should result in their more widespread clinical use, they write.

“Together, we anticipate that in the next 10-20 years these advances will lead to a wave of new clinical therapies for musculoskeletal disorders,” the paper concludes.

Among the treatment challenges moving forward, Guyer said, will be both narrowing the different therapeutic strategies that are available as well as combining them to meet the complex needs of patients.

“One research challenge is developing patient-specific approaches to treating these different kinds of tissues holistically,” Guyer said. “Combining the different treatments we have for cartilage, bone and muscle, and treating the entire injury or disorder as a whole, as opposed to just focusing on one type of tissue at a time.”

For Guyer, a third year Ph.D. student in the Guldberg Lab, contributing to the paper presented an opportunity to delve deeper into research both inside and outside of his own area of expertise. Guyer’s research examines the body’s immune response to trauma, particularly to bone trauma.

“I get to work with bone and muscle, but also with the immune system, which affects the entire body, so a lot of the work that we do kind of mingles with work from other fields too,” Guyer said. “Since the immune system affects countless different processes, there are a lot of intersections.”

Contributing authors on the paper include Axel C. Moore, now a research scientist at the University of Delaware; Molly M. Stevens, a professor of biomedical materials and regenerative medicine at Imperial College London; and Nenad Bursac, a professor of biomedical engineering at Duke University.


This work was supported by the Wu Tsai Human Performance Alliance and the Joe and Clara Tsai Foundation.