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AN INJECTABLE CELL-SEEDED HYDROGEL FOR THE TREATMENT OF SPINAL DISC DEGENERATION

Institute of Orthopaedics and Musculoskeletal Science, Royal Free and University College Medical School and Royal National Orthopaedic Hospital, Stanmore, UK

Study Purpose: 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 three-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 alginates 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 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.

Conclusions: Both CaCO3 alginate gel and CaSO4 alginate gel are injectable and are capable of sustaining NP cells in-vitro. Cells remain viable, maintain their phenotype, proliferate and produce ECM during the culture period. The CaCO3 alginate gel provides a three-dimensional matrix more favourable to NP cellular activity than the CaSO4 alginate gel. Synvisc® behaves as a chondro-stimulant significantly enhancing NP cell metabolic activity. 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.

Correspondence should be addressed to Dr Carlos Wigderowitz, Honorary Secretary of BORS, Division of Surgery & Oncology, Section of Orthopaedic & Trauma Surgery, Ninewells Hospital & Medical School Tort Centre, Dundee, DD1 9SY.