Disc-Facet Crosstalk During Spinal Degeneration and Repair

The anterior intervertebral disc and posterior diarthrodial facet joints form what is referred to the three-joint complex of the spine, working in concert to resist large magnitude axial loads and constrain range of motion to non-injurious levels. Degenerative pathology in both spinal structures is a known contributor to back pain, which

has become the number one cause of years lived with disability globally. Intervertebral disc degeneration is associated with structural and biochemical changes to the disc tissues, which compromise the ability of the disc to bear load, potentially leading to overloading of the facet joints. The study of disc degeneration has been

dominant in the field for decades, and as such, little is known the pathophysiology of facet osteoarthritis (OA), or how altered disc mechanical function may contribute to the progression of facet degeneration. This proposal will bring a new perspective to the study of spinal degeneration by investigating the mechanical crosstalk between

the disc and its adjacent facet joints during degenerative processes and in the scenario of disc repair, using animal models and human tissues. In Aim 1A, we will first utilize a large animal model to characterize the progression of facet OA in an initially healthy spine following experimentally induced degeneration of the adjacent

discs. Facet cartilage and subchondral bone pathology will be probed across length scales as a function of disc degeneration to determine the temporal relationship between disc degeneration and facet OA. In Aim 1B, we will also utilize human cadaveric tissues to determine how facet pathobiology and disc-facet crosstalk differ in

males versus females, factors less easily studied in large animal models. In both goat experimental and human cadaveric tissues, we will assess inflammation, innervation and immune cell infiltration into the disc and facet joint synovium and capsule as surrogate measures of pain and biological dysfunction. Finally, quantitative

structure-function outcomes from both goat and human spinal tissues (Aims 1A and B) will then be utilized to generate patient/animal-specific finite element models, which will be used to quantify stress distributions in the facet joints under simulated six degree of freedom physiologic loading to understand mechanistically how altered

disc mechanical function during degeneration may contribute to the progression of facet OA. In Aim 2, we will then elucidate whether restoring intervertebral disc mechanical function can mitigate the progression of disc degeneration and facet OA. Using the same large animal model as Aim 1, we will deliver an injectable, granular

hyaluronic acid hydrogel to the degenerative nucleus pulposus to acutely augment disc mechanical properties. The acute effects of NP augmentation via the granular hydrogel on facet loading will be assessed using the animal-specific finite element models utilized in Aim 1. The extent of disc repair and concomitant progression of

facet OA in vivo will be assessed across length scales via a variety of structure-function outcomes. Overall, the knowledge gained from this study of disc-facet crosstalk can contribute to developing advanced diagnostics for spinal degeneration and elucidating new targets for tissue engineering and regenerative medicine strategies.