Anti-Inflammatory Tension-Activated Repair Patches Improve Repair After Intervertebral Disc Herniation

Peredo, A. P.; Gullbrand, S. E.; Friday, C. S.; Orozco, B. S.; Bonnevie, E. D.; Hilliard, R. L.; Zlotnick, H. M.; Dodge, G. R.; Lee, D.; Hast, M. W.; Schaer, T. P.; Smith, H. E.; Mauck, R.

doi:10.1101/2022.10.22.513360

bioRxiv · 10.1101/2022.10.22.513360

Anti-Inflammatory Tension-Activated Repair Patches Improve Repair After Intervertebral Disc Herniation

Peredo, A. P.·Gullbrand, S. E.·Friday, C. S.·Orozco, B. S.·Bonnevie, E. D.·Hilliard, R. L.·Zlotnick, H. M.·Dodge, G. R.·Lee, D.·Hast, M. W.·Schaer, T. P.·Smith, H. E.·Mauck, R.

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Abstract

Conventional treatment for intervertebral disc herniation alleviates pain but does not repair the annulus fibrosus (AF), resulting in a high incidence of recurrent herniation and persistent disfunction. The lack of repair and the acute inflammation that arise after injury further compromises the disc and can result in disc-wide degeneration in the long term. To address this clinical need, we developed tension-activated repair patches (TARPs) for annular repair and the local delivery of bioactive anti-inflammatory factors. TARPs transmit physiologic strains to mechanically-activated microcapsules (MAMCs) embedded within, which activate and release encapsulated biomolecules in response to physiologic loading. Here, we demonstrate that the TARP design modulates implant biomechanical properties and regulates MAMC mechano-activation. Next, the FDA-approved anti-inflammatory molecule, interleukin 1 receptor antagonist, Anakinra, was loaded in TARPs and the effects of TARP-mediated annular repair and Anakinra delivery was evaluated in a model of annular injury in the goat cervical spine. TARPs showed robust integration with the native tissue and provided structural reinforcement at the injury site that prevented disc-wide aberrant remodeling resulting from AF detensioning. The delivery of Anakinra via TARP implantation improved the retention of disc biochemical composition through increased matrix deposition and retention at the site of annular injury. Anakinra delivery additionally attenuated the inflammatory response associated by scaffold implantation, decreasing osteolysis in adjacent vertebrae and preserving disc cellularity and matrix organization throughout the AF. These results demonstrate the translational and therapeutic potential of this novel TARP system for the treatment of intervertebral disc herniations. One Sentence SummaryTension-activated repair patches delivering bioactive anti-inflammatory factors improve healing in an in vivo goat cervical disc injury model.

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Peredo, A. P., Gullbrand, S. E., Friday, C. S., Orozco, B. S., Bonnevie, E. D., Hilliard, R. L., Zlotnick, H. M., Dodge, G. R., Lee, D., Hast, M. W., Schaer, T. P., Smith, H. E., Mauck, R.. 2022-10-23. Anti-Inflammatory Tension-Activated Repair Patches Improve Repair After Intervertebral Disc Herniation. https://doi.org/10.1101/2022.10.22.513360

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