In an era of escalating death and damage from the opioid epidemic, innovative solutions to prevent the more than 130 daily U.S. deaths from opioid overdose are a national priority. Within this context, a major focus area for the healthcare industry is to better understand the underlying causes of chronic pain and establish pain management strategies that avoid the risks of opioid addiction—and a research team from the Massachusetts Institute of Technology (MIT) recently took this quest to space.
Of the more than 50 million Americans living with chronic pain, nearly 6 million suffer from long-term osteoarthritis that results from a previous joint injury. Vehicle accidents, sports injuries, and other sources of joint trauma can lead to post-traumatic osteoarthritis (PTOA), even in young adults. Approximately 50% of individuals with knee injury develop PTOA within 10 years, and 30% of military personnel develop PTOA from combat injuries.
Sadly, restoring joint stability via anterior cruciate ligament (ACL) reconstruction in the knee, for example, does not reduce the risk of developing PTOA. In fact, there is currently no approved therapy to prevent the lifelong pain and dysfunction of PTOA, which is a leading cause of disability worldwide. The MIT investigation, led by Alan Grodzinsky, launched to the ISS National Lab in May and seeks to develop a new approach to preventive care for PTOA.
Little is known about the molecular mechanisms underlying PTOA initiation and progression, but inflammation occurring immediately after joint injury appears to play a key role in the onset of chronic PTOA. The inflammation will resolve for some, but for others, the silent damage continues despite the absence of symptoms and apparent progress toward recovery. Previous PTOA research on trauma to cartilage has largely ignored the complex biomechanics involved in inflammation—some of which may be key to early medical intervention.
Grodzinsky’s team is using a different approach: a tissue chip containing multiple cell types to mimic the fundamental biomechanics of how bone and cartilage move and interact with the synovial membrane (the joint-lining tissue that produces a lubricating fluid). The team’s ISS National Lab experiment validated this tissue chip model both on the ground and in space, where bone and cartilage damage may be accelerated.
In orbit, the team exposed the tissue chip to pro-inflammatory molecules, simulated an impact injury, tested several therapeutics, and preserved samples of cells and secreted molecules at several experimental stages for postflight analysis. They used tissues from different donor individuals in these studies to characterize complex tissue chip responses to both “injury” and response to therapy.
The study holds the potential for new biomarker discovery that will enable early diagnosis and reveal the mechanisms that underlie individual variability in response to both injury and treatment. Successful preventive treatment following injury, during the 10 to 20 years of asymptomatic damage in at-risk individuals, could potentially drastically reduce the number of patients who develop chronic pain.
This type of early intervention is common in the management of diabetes, heart disease, and osteoporosis, but for those individuals suffering from chronic pain, preventive medicine is still beyond reach. Creative and advanced biomedical approaches to studying disease—on Earth and in space—can hopefully provide nonopioid relief to the military personnel, student athletes, and millions of others afflicted by PTOA or other causes of chronic pain.
Grodzinsky’s ISS National Lab project is one of several tissue chip studies co-sponsored by the National Institutes of Health’s National Center for Advancing Translational Sciences (NIH NCATS), complementing other spaceflight tissue chip experiments co-sponsored by NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the National Science Foundation (NSF).
This content was abridged from an article that originally appeared on issnl.us/ISS360
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