# Disc-Facet Crosstalk During Spinal Degeneration and Repair

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $605,253

## Abstract

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 progressio...

## Key facts

- **NIH application ID:** 10980071
- **Project number:** 1R01AR083007-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** SARAH E GULLBRAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $605,253
- **Award type:** 1
- **Project period:** 2024-09-26 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980071

## Citation

> US National Institutes of Health, RePORTER application 10980071, Disc-Facet Crosstalk During Spinal Degeneration and Repair (1R01AR083007-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10980071. Licensed CC0.

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