In Preclinical Research, a Tension-Activated “Patch” Reversed Disc Herniation

The photo above shows an image of a TARP, a tension-activated repair patch, courtesy of Penn Medicine.

A new biologic “patch” that is activated by the natural motion of the spine could be the key to repairing herniated discs, according to researchers at the Perelman School of Medicine at the University of Pennsylvania and the CMC VA Medical Center (CMCVAMC).

The “tension-activated repair patch” (TARP) provides controlled release of an anti-inflammatory molecule called anakinra from microcapsules over time, which helped discs in a large animal model regain the tension needed to reverse herniation and prevent further degeneration.

This preclinical research is detailed in a paper published in Science Translational Medicine.

“Currently there is no curative treatment for disc herniation, and the best thing out there is just like sticking a plain rubber plug into a hole in a tire. It will stay for a while, but it won’t make a great seal,” said co-senior author Robert Mauck, PhD, a professor in Orthopaedic Surgery and director of the McKay Laboratory for Orthopaedic Surgery Research at Penn and research career scientist and co-director of the Translational Musculoskeletal Research Center at the CMCVAMC.

“The patch we’ve developed is like the plug plus glue, so you’re actually bonding the patch. And since biomechanical movement activates the patch and makes it seal more strongly, it’s like having your tire patch get stronger the more miles you put on it.”

Restoring Disc Integrity

Herniation in the spine occurs when one of the soft discs that sits between the vertebrae develops a split or a hole, and the soft interior squeezes through. This means that the discs lose their tension and are unable to cushion the spine as usual, causing pain. To continue the tire analogy, it’s as if a tire has gone flat and the car is riding on its rim.

The Penn Medicine and CMCVAMC researchers have developed TARPs to not just plug the hole, but also to allow tension to build back up and re-cushion the vertebrae. That goal has been particularly tough to achieve to this point.

“The disc is a very complex tissue, which is different from muscle and skin in that it cannot heal its own structure and, in fact, continues to degenerate over time once its structure is compromised,” said Ana Peredo, PhD, who completed this research during her doctoral studies in Bioengineering at the School of Engineering and Applied Sciences at Penn.

“We set out to recover the disc’s mechanical integrity while simultaneously attenuating inflammation in order to prevent further tissue damage and retain as much tissue function as possible.”

An Early Intervention

Key to the TARP is having the body’s natural mechanics work to activate the release of anti-inflammatory molecules from the microcapsules within the patch. Although they would theoretically still work if a person lay totally still for months, the reality of the disc tissue environment is that movement is its natural state.

And because the patch makes it as if there was never a hole to begin with, its application could have significant effects on the prevention of worsening pain related to disc degeneration.

“This is designed to be an early intervention that may change the course of disease progression,” said co-senior author Harvey Smith, MD, an associate professor of Orthopaedic Surgery and attending physician at the CMCVAMC.

“Currently there’s no treatment to mitigate recurring herniations that actually heal the disc. So, we’re looking at a disease that is very common in younger, working-age people that, downstream, leads to severe disc disease and the need for spinal fusion. The more we can prevent that, the better.”

Early Research Stage

Although this research was primarily “proof of principle,” moving this treatment closer to the clinic will require longer trials in large animal models, the team said.

“This study was incredibly promising but went for 1 month, so we want to test for a longer time because there are ways we can fine-tune this patch,” said co-lead author Sarah Gullbrand PhD, a research assistant professor of Orthopaedic Surgery at Penn and research health scientist at the CMCVAMC.

“We only targeted 1 biologic pathway this time using something that was already approved by the FDA, but there are tons of other factors that are approved. In the future, we’re interested in not only reducing inflammation, but also preventing cell death and improving overall healing.”

The research was funded by the Department of Veterans’ Affairs Rehabilitation Research and Development Service (I21 RX003447, IK6 RX003416, IK2 RX003118) and the National Institutes of Health (R01 AR071340) and was supported by the Penn Center for Musculoskeletal Disorders (P30 AR069619).

Source

Peredo AP, Gullbrand SE, Friday CS, et al. Tension-activated nanofiber patches delivering an anti-inflammatory drug improve repair in a goat intervertebral disc herniation model. Science Translational Medicine. 15 Nov 2023;15(722). doi: 10.1126/scitranslmed.adf1690

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