Development and Characterization of a Chemically Crosslinked Polyvinyl Alcohol/Polyethylene Glycol Hydrogel for Injectable Nucleus Pulposus Replacement

Low back pain caused by intervertebral disc degeneration is one of the most common spinal disorders among patients seeking medical treatment. The most common surgical treatments for disc degeneration are spinal fusion and total disc arthroplasty; both of which are very invasive surgical procedures. Spinal fusion results in a loss of spinal mobility and increased stress on adjacent intervertebral discs and while total disc arthroplasty retains spinal mobility it is not FDA approved for multilevel replacement. Nucleus pulposus replacement is an earlier stage intervention for disc degeneration before multilevel interventions are necessary. One of the material classes being studied for this application is hydrogel: a three-dimensional hydrated network of polymer(s), which mimics the mechanical and physiological properties of the nucleus.;Previous nucleus replacement materials have included the poly(N-isopropylacrylamide) (PNIPAAm) class of hydrogels and poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) hydrogels; the PNIPAAm hydrogel disadvantages are the mechanical properties and implant shrinkage. While the PVA/PVP have the desired mechanical properties, they are molded into string form and injected percutaneously through a cannula. Due to this implantation method, there are issues with implant movement and expulsion from the injection site. This is due to the fact that the implant is a coiled string. PVA, PVP and poly (ethylene glycol) (PEG) hydrogels have previously been shown to be great candidate materials for injectable nucleus pulposus replacement, but have experienced issues with swelling and mass retention. The addition of chemical crosslinking to the PVA/PVP/PEG hydrogel system will allow tailoring of the swelling, mechanical, injectability and mass loss properties of the hydrogel network. Two chemical crosslinking methods were evaluated for the PVA/PVP/PEG hydrogel system, resulting in the selection of a difunctional crosslinking strategy using PEG functionalized with terminal epoxide group (PEG diglycidyl ether) (PEG-DGE). The PVA/PVP/PEG-DGE hydrogel system was characterized by compression and swelling experiments and then the structure-property relationship was determined with the addition of morphology, spectroscopy and crystallinity analysis. A purification technique was developed and optimized to reduce the mass loss of the hydrogel network and then the structure-property relationship of the new purified gel was investigated due to a change in the gelation mechanism of the network after purification. The unpurified and purified hydrogel formulations have mechanical and swelling properties in the desired range for nucleus replacement, in addition, the purified hydrogel showed low cytotoxicity. Also, the swelling mechanics of the hydrogel formulations were characterized in model osmotic solutions to simulate the intradiscal environment.