A NOVEL INJECTABLE CELLULAR POLYMER FOR THE TREATMENT OF SPINAL DISC DEGENERATION

Abstract

Background: The cause of intervertebral disc degeneration (IVDD) is multifactorial. One proposed mechanism is that IVDD originates in the nucleus pulposus (NP) and progresses radially to the annulus fibrosis (AF). Failure of current treatment modalities in preventing and treating IVDD and thereby low back pain have led to a growing interest in tissue-engineered solutions where a biological repair is induced. By preventing the abnormality at the NP it may be possible to halt further progression of IVDD. Injection of NP cells into an early degenerative IVD, where the AF is still intact, may retard the degenerative process and is presently under investigation. Using a 3-dimensional scaffold that could be successfully introduced into the NP cavity through minimally invasive techniques would prevent the loss of chondrocytic phenotype of the cells and be an improvement over the existing technique by which cells are directly injected into the NP cavity.

Methods:

1. CaSO4 and CaCO3 3% alginate hydrogels were injected into the NP cavity of a bovine tail. After 90 minutes the tail was dissected to reveal the gel.

2. NP cells released from pooled bovine NP tissue were dispersed into the CaSO4 and CaCO3 alginate gels (10x106 cells.mL-1) with and without hylan (Synvisc®) and cultured for 21 days.

Results:

1. Injectable alginate suspensions formed solid viscoelastic gels, filling the exact shape of the NP cavity.

2. NP DNA and ECM synthesis was significantly greater in the CaCO3 alginate gel than in the CaSO4 alginate gel (p< 0.05).

3. Synvisc® significantly increased sulphated GAG (p< 0.01) and collagen (p< 0.05) production. These effects were supported histologically and immunohistologically where cells in the CaCO3 and Synvisc® gels stained more intensely for proteoglycan and collagen type II.

Discussion: This study demonstrates that slowly polymerising CaCO3 and CaSO4 alginate gels are injectable and capable of sustaining NP cells in-vitro. Cells remain viable, maintain their phenotype, proliferate and produce ECM during the culture period. CaCO3 alginate gel provides a 3-dimensional matrix more favourable to NP cellular activity than the CaSO4 alginate gel. Synvisc® has a chondro-stimulatory effect on NP cells in-vitro. These effects are similar to those observed previously with hyaluronic acid, in that it binds to cell surface CD44 receptors, thereby affecting essential cellular functions and cytoskeleton structure. Synvisc® however has an advantage in that it is highly viscous and can reside longer within an alginate construct thereby having a sustained long-term stimulatory effect. This study demonstrates a successful tissue-engineered approach for replacing the NP and, subject to further studies, may be used for retarding mild-to-moderate IVDD, alleviating lower back pain and restoring a functional NP through a minimally invasive technique.