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Conventional microdiscectomy treatment for intervertebral disc herniation alleviates pain but does not repair the annulus fibrosus, resulting in a high incidence of recurrent herniation and persistent dysfunction. The lack of repair and the acute inflammation that arise after injury can further compromise the disc and result in disc-wide degeneration in the long term. To address this clinical need, we developed tension-activated repair patches (TARPs) for annulus fibrosus repair and local delivery of the anti-inflammatory factor anakinra (a recombinant interleukin-1 receptor antagonist). TARPs transmit physiologic strain to mechanically activated microcapsules embedded within the patch, which release encapsulated bioactive molecules in direct response to spinal loading. Mechanically activated microcapsules carrying anakinra were loaded into TARPs, and the effects of TARP-mediated annular repair and anakinra delivery were evaluated in a goat model of annular injury in the cervical spine. TARPs integrated with native tissue and provided structural reinforcement at the injury site that prevented aberrant disc-wide remodeling resulting from detensioning of the annular fibrosus. The delivery of anakinra by TARP implantation increased matrix deposition and retention at the injury site and improved maintenance of disc extracellular matrix. Anakinra delivery additionally attenuated the inflammatory response associated with TARP implantation, decreasing osteolysis in adjacent vertebrae and preserving disc cellularity and matrix organization throughout the annulus fibrosus. These results demonstrate the therapeutic potential of TARPs for the treatment of intervertebral disc herniation. Editor's summary: Microdiscectomy, the primary treatment for herniated intervertebral discs (IVDs), does not stabilize the disc structure or improve repair, leading to degeneration and frequent recurrence. Peredo et al. engineered a nanofiber repair patch and tested it in goats with cervical IVD injury. The patches integrated with surrounding tissue providing structural support and improving injured disc closure. The patches also delivered an anti-inflammatory biologic, anakinra, that was released in response to normal spinal motion. The authors reported decreased IVD degeneration after 1 month in the goat model with local release of anakinra further preserving disc structure and organization. These findings support further investigation of this multifunctional approach to treat IVD herniation. —Molly Ogle [ABSTRACT FROM AUTHOR]

Tissue-engineered intervertebral discs demonstrate long-term functional integration in rat and goat disc replacement models. Dependable discs: Intervertebral disc degeneration causes back and neck pain, sometimes necessitating disc fusion surgery. Although fusion may alleviate symptoms, it does not address the underlying cause of degeneration. As an alternative to fusion, Gullbrand and colleagues developed tissue-engineered discs for disc replacement by sandwiching hydrogel and polymer materials seeded with cartilage or mesenchymal stem cells between acellular polymer endplates. Engineered discs integrated with native discs, maintaining their structure and showing near-native mechanical properties 5 months after implantation in a rodent disc replacement model. Similar results were seen 2 months after implantation in a goat model, demonstrating the translational feasibility of this tissue engineering approach. Tissue engineering holds great promise for the treatment of advanced intervertebral disc degeneration. However, assessment of in vivo integration and mechanical function of tissue-engineered disc replacements over the long term, in large animal models, will be necessary to advance clinical translation. To that end, we developed tissue-engineered, endplate-modified disc-like angle ply structures (eDAPS) sized for the rat caudal and goat cervical spines that recapitulate the hierarchical structure of the native disc. Here, we demonstrate functional maturation and integration of these eDAPS in a rat caudal disc replacement model, with compressive mechanical properties reaching native values after 20 weeks in vivo and evidence of functional integration under physiological loads. To further this therapy toward clinical translation, we implanted eDAPS sized for the human cervical disc space in a goat cervical disc replacement model. Our results demonstrate maintenance of eDAPS composition and structure up to 8 weeks in vivo in the goat cervical disc space and maturation of compressive mechanical properties to match native levels. These results demonstrate the translational feasibility of disc replacement with a tissue-engineered construct for the treatment of advanced disc degeneration. [ABSTRACT FROM AUTHOR]