The Role of Nutrient Pathway in Lumbar Intervertebral Disc Allograft After Transplantation

This dissertation, "The Role of Nutrient Pathway in Lumbar Intervertebral Disc Allograft After Transplantation" by Yongcan, Huang, 黃永燦, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: The success of fresh-frozen intervertebral disc allograft transplantation in the human cervical spine has opened up a new dimension in the treatment of disc degenerative diseases. Nevertheless, technical improvements are still needed, because a mild degeneration of the postoperative disc allograft has been found. The course and aetiology of disc allograft degeneration are unclear, but loss of nutrient supply is likely one of the most important factors. This is because the disc allografts are immersed in the ischaemic environment until the nutrient pathway is re-established. Understanding the nutrient reestablishment and the degenerative profile of the postoperative disc allograft is essential for the development of reparative strategies. Thus, the aim of this study was to determine the reestablishment of the nutrient pathway and its role in the degeneration of the postoperative disc allograft. All of the experiments were performed in the goat lumbar spine. A surgical technique for disc allografting was developed; the heights of the postoperative disc allograft and its adjacent levels, as well as the segmental and global mobility, were measured to validate the feasibility of the goat model. Second, the reestablishment of nutrient pathway in the postoperative disc allograft was determined by healing of the host-graft interfaces, remodelling of the endplates and the revascularisation at 1.5, 6 and 12 months after transplantation. Third, the degenerative process of the disc allograft during the reestablishment of the nutrient pathway was evaluated through gross morphology, cell behaviours and the extracellular matrix. Disc allografting without internal fixation was successfully performed in the goat lumbar spine. Motion preservation and reduction of the disc allograft height were found after 12 months; this closely resembled what has been observed in human cases. Thus, this model was suitable for subsequent experiments. As the prerequisite to the stability of lumbar spine and the reestablishment of the nutrient pathway, healing of the host-graft interfaces was completed after 6 months. Nevertheless, alteration of the nutrient transportation pattern was seen because the bony endplate was replaced by trabecular bone and the cartilaginous endplate basically disappeared; the other reason for this was that host blood vessels were seen surrounding the cartilaginous centre after 12 months. Furthermore, a time lag for nutrient reestablishment was evident according to the process of revascularisation and the remodelling of the endplates. Therefore, the re-established nutrition pattern of the disc allograft differed significantly from that in normal discs. This re-established nutrient pathway ensured the viability of the disc allograft, but led to structural remodelling. After 12 months, the gelatinous nucleus was replaced by the regenerated fibrocartilage and enclosed by the disorganised annulus connecting the adjacent vertebral bodies to form a "bone-fibrocartilage- bone" structure. Although a transplanted disc allograft was able to provide adequate stability and mobility of the lumbar spine for clinical function, it was histologically far from being normal. This could be partly caused by the ischaemic insult until the nutrient pathway is re-established through the endplates. Future research should therefore focus on how to enhance nutrition delivery postoperatively