Degeneration of the intervertebral discs is the most common cause of back pain. The
early stages of degeneration affect the nucleus pulposus (NP) of the intervertebral discs
followed by a rapid degeneration of the annulus fibrosus. Regeneration of the NP may
slow down or reverse the progression of the disease. A new deacetylated derivative of a
marine diatomic glycosaminoglycan was developed to obtain a hydrogel formulation
proposed to have a reparative effect on damaged NP tissue. The hydration kinetics and
viscoelastic behaviour of the hydrogel under shear were studied and compared with the
behaviour of nondegenerated human lumbar NP. In vitro studies were conducted using
primary cell cultures treated with the drug to study cell viability and extracellular matrix
factor expression. In vivo studies using New Zealand White (NZW) rabbits have also
been conducted using MRI to quantify disc volume followed by histological and
immunohistochemical analysis. Rheological data has indicated that the elastic component
of the hydrogel dominates the viscous component over a frequency range of 0.1 to 15.85
rad/s. Proteoglycan expression of the treated cells was found to be 78.4 ± 1.9 (p<0.05)
times higher than the untreated controls. RTPCR and immunohistochemical data from in
vitro studies have demonstrated that characteristic the chondrocyte markers, aggrecan and
collagen II, are expressed in the treated cells. A comparison of disc volumes at 6 weeks
post-op has shown that the treated discs have 41% greater volume than the untreated
iii
discs (p<0.05). The results obtained in this study demonstrate that the sulfated
deacetylated glycosaminoglycan derivative is a promising material to be utilized in
treatment of NP degeneration.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/17172 |
| Date | 24 February 2009 |
| Creators | Gorapalli, Deepthi |
| Contributors | Whyne, Cari, Yee, Albert |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
| Format | 1606024 bytes, application/pdf |
Page generated in 0.0022 seconds