Tension-activated nanofiber patches delivering an anti-inflammatory drug improve repair in a goat intervertebral disc herniation model

Abstract

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.

TNFR1-mediated senescence and lack of TNFR2-signaling limit human intervertebral disc cell repair in back pain conditions

“…However, cell therapies for IVD repair are challenging because autologous cells may be more susceptible to microenvironmental stress and die after re-injection, and if they survive would compete with resident IVD cells in the limited nutrient environment of the IVD ( 49, 61 ). Therefore, consideration of biomaterials or engineered constructs such as recently developed bioactive tension-activated nanofiber patches that can modulate pro-inflammatory responses through IL1-β pathway may be required ( 62 ).Those approaches can also target TNFR1 or otherwise protect delivered and native IVD cells from the complex pro-inflammatory environment of the IVD.…”

“…Regardless, immunomodulation of native IVD cells likely offers more promise for translation since IVD cells are present in much greater numbers than immune cells in the IVD. For example, recently developed bioactive tension-activated nanofiber patches can modulate IVD pro-inflammatory responses through the IL-1β pathway (73), and such approaches can be modified to target additional cytokines and receptors to modulate IVD cell response to the complex IVDD CM environment.…”

Temporal control in shell–core structured nanofilm for tracheal cartilage regeneration: synergistic optimization of anti-inflammation and chondrogenesis

“…For instance, Peredo et al . improved goat intervertebral disc herniation by loading anti-inflammatory drugs onto electrospun membranes [ 14 ]. Furthermore, the development of coaxial electrospinning technology has enabled the creation of multifunctional nanofilms with timed-release core–shell structures [ 15 ].…”