An international collaboration that includes an Oregon State University researcher has used a new three-dimensional X-ray imaging approach to better understand the spinal structures whose degeneration leads to debilitating back pain for hundreds of millions of people.
The findings, underpinned by a biomechanics evaluation method developed by co-author Brian Bay of the OSU College of Engineering, were published today in Nature.
The deep dive into how intervertebral discs respond to the mechanical forces caused by everyday movements opens the door to possible new treatments in the coming years for what the World Health Organization calls the single leading cause of disability worldwide.
"The results suggest a fundamental issue with spinal discs that may influence the way we think about disc degeneration and methods for prevention and mitigation," said Bay, associate professor of mechanical engineering. "Even though the bulk of this manuscript uses a small-animal model, the end is a demonstration of feasibility with actual human samples. That really gets at the crux of the problem from a research standpoint."
The human spine has 23 discs, acting as shock absorbers that provide protection and facilitate flexibility as a person walks, runs, sits, stands, etc. Each disc has two parts: a sturdy outer ring known as the annulus fibrosus, and a center area, the nucleus pulposus, that contains a soft, gel-like material.
It's long been known that disc damage and age-related degeneration are major contributors to back pain, Bay said, but the details of disc mechanics have largely remained a mystery.
"It has not been clear why discs tend to degenerate and fail, and most interventions are salvage operations," he said.
Much of the prior research, he explained, was either at the large scale - the general biomechanical function of an intact disc - or the small scale; that is, a detailed evaluation of small, extracted tissue samples.
"But nothing connected the two - the clinical problem was isolated from the molecular and cellular level," Bay said. "This work makes that bridge in what I think is a very elegant way. The methodology, known as fiber-traced digital volume correlation or DVC, provides exactly the information needed for the connection."
DVC, developed by Bay in 2000, is a widely-used technique that lets scientists observe, in three dimensions, how tissue deforms when forces are applied to it. Fiber-traced DVC, developed in collaboration with Catherine Disney, a post-doctoral researcher at the University of Manchester, extends the basic DVC technique by tracking the deformation and movement of collagen fiber bundles and individual collagen fibers within tissue; collagen, the most abundant protein in the human body, is a primary structural building block.
"Fiber-traced DVC provides data necessary for analysis at the nanoscale and is a conduit for linking small-scale results to the clinical scale," Bay said. "The findings also point to a potential tradeoff in the way discs are built: We found evidence that substantial strain may help a disc achieve the stiffness it needs to perform its role, but it also may move the tissue closer to damaging strain levels, contributing to its vulnerability over time."
The study's novel imaging approach, known as TomoSAXS, showed that the strain varies across the layered structure of the disc, he added, and is closely related to how individual fibers respond to loading.
The paper, Bay said, is a result of years of collaborating with scientists at Queen Mary University of London, University College London, Royal Veterinary College, the University of Manchester, and Diamond Light Source, the United Kingdom's national synchrotron light source science facility.
"This is mechanics of materials taken to an extreme - in other words basic mechanical engineering and materials science," Bay said. "Retreat has been happening recently from these basic disciplines, yet they remain very important in new discovery."
By connecting structures ranging from individual molecules to whole organs, the researchers hope to uncover where mechanical damage begins and how it develops - providing a stronger foundation for new research.
In the future, TomoSAXS could be used to investigate how the structure and mechanical behavior of discs change with aging and disease and to evaluate potential therapies or new approaches to repairing or replacing damaged discs, Bay said.
It could also be applied to other fibrous biological tissues, including tendons, cartilage and arteries, as well as engineered materials such as carbon-fiber composites.
Himadri Gupta and Elis Newham of Queen Mary University of London and Peter Lee and Alissa Parmenter of University College London are the study's corresponding authors.
Funding was provided by the UK Engineering and Physical Sciences Research Council, the UK Medical Research Council, the Royal Academy of Engineering, the Chan Zuckerberg Initiative and Diamond Light Source.
