Files

Abstract

Intervertebral disc degeneration is a major reason why we experience low back pain. Intervertebral discs are located in-between the vertebrae of the spine. They act, among other, as shock absorbers by distributing the mechanical load applied to the spine while giving it its range of motion. An intervertebral disc is composed of a center - a soft core, called nucleus pulposus which is surrounded by a strong ring called the annulus fibrosus. By disc degeneration, we mean a physical deterioration of either the nucleus and/or the annulus. It has been posited that low back pain could be alleviated by replacing the degenerated nucleus pulposus by a synthetic implant. However, such nucleus pulposus replacements have been subjected to highly controversial discussions over the last 50 years and their use has not yet resulted in a positive outcome to treat degenerated disc disease. In this thesis, we report on the development of an implant material consisting of poly(ethylene glycol)dimetacrylate - a hydrogel - loaded with nano-fibrillated cellulose. Photopolymerization was selected as a polymerization method to "harden" the implant in situ. Thus, the implant can be injected in a liquid state through the annulus fiborsus with a small diameter cannula. Furthermore, an in situ photopolymerization method was developed along with an implanting device which was used to insert the composite hydrogel into an intervertebral disc ex vivo. The volume of a human nucleus pulposus is several 100 cubic millimeters, which is a substantial volume to photopolymerize. In order to ensure a homogeneous photopolymerization of this volume, a Monte Carlo model was developed. The model is able to predict accurately the volume of the photopolymerized implant in tissue cavities. This simulation tool was used to tailor the light scattering properties of the hydrogel by loading it with lipid particles. Thus, spherical implant shapes could be photopolymerized. An implanting device was developed to inject and photopolymerize the liquid implant while monitoring the cross-linking reaction of the implant during photopolymerization using fluorescence spectroscopy in situ and in real-time. Using this device, synthetic nucleus pulposus implants were successfully inserted through a 1 mm incision in the annulus fiborsus of an ex vivo bovine intervertebral disc model and the long-term performance of the proposed nucleus pulposus replacement was evaluated. The changes of the fluorescence signal throughout the photopolymerization reaction could be shown to correlate with the photopolymerization volume. It was thus possible to insert the synthetic implant in a controlled manner into the bovine disc model. The implant was able to significantly re-establish intervertebral disc height after surgery (p < 0.0025) and maintain it over 0.5 million loading cycles (p < 0.025). Disc height is one of the essential parameters to restore and maintain in an intervertebral disc. The excellent results achieved in these ex vivo experiments validated the implantation method and the device. More importantly, they showed that the novel implant material might resist mechanical loads similar to the loads that would be experienced in everyday life. However, longer tests (~ 10 million cycles) are required to determine whether this material would truly resists during a clinical study.

Details

Actions

Preview