Yonemura, Susan S., authorJames, Susan P., advisorBailey, Travis S., committee memberKisiday, John D., committee memberWheeler, Donna L., committee member2007-01-032012-06-012011http://hdl.handle.net/10217/52135Degenerative disc disease (DDD) is an inevitable consequence of aging, commonly resulting in low back pain (LBP). Current clinical treatment options for disc degeneration exist at two extremes: conservative management or extensive surgical intervention. Given the economic impact of lost productivity and disability associated with low back pain, there is significant interest in earlier, less invasive intervention. Biomimetic disc replacement and regenerative therapies offer an attractive alternative strategy for intervertebral disc repair, but materials employed to date have not exhibited a successful combination of mechanical and biological properties to achieve viable solutions. The composite material developed and characterized in this work consisted of a novel hyaluronan-co-poly(ethylene-alt-maleic anhydride) (HA-co-PEMA) hydrogel matrix reinforced with nanoparticulate silica; the hydrogel matrix provided a compliant hydrated matrix conducive to integration with the surrounding tissue while the nanoparticulate reinforcement was manipulated to mimic the mechanical performance of healthy ovine nucleus pulposus (NP) tissue. HA-co-PEMA was formed via an esterification reaction between a hydrophobically-modified HA complex and PEMA, and candidate formulations were characterized by chemical, thermal, and physical means to select an appropriate base hydrogel for the reinforced composite. Three grades of commercially-available fumed silica, varying by degree of hydrophobic surface modification, were evaluated as nanoparticulate reinforcement for the composite materials. Mechanical testing of two reinforced composite formulations (620-R and 720-R) emphasized dynamic shear properties and results were directly compared to ovine nucleus pulposus (NP) tissue. The complex shear modulus (G*) for 620-R ranged from 1.8±0.2 KPa to 2.4±0.3 KPa over the frequency range 0.1 Hz < f < 10 Hz, while G* for 720-R varied from 4.4 ± 0.5 KPa to 6.1 ± 0.6 KPa over the same frequency range. Ovine NP tissue tested using identical methods exhibited G* of 1.7 ± 0.2 KPa at 0.1 Hz up to 3.8 ± 0.5 KPa at 10 Hz. Thus, the complex shear moduli (G*) for 620-R and 720-R effectively bracketed G* for NP over a physiologically-relevant frequency range. Subsequent in vitro cytotoxicity and biocompatibility experiments suggest that the 720-R formulation warrants consideration for future in vivo modeling.born digitaldoctoral dissertationsengCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.compositeintervertebral dischydrogelhyaluronandynamic shearrheometryText