Degeneration of the intervertebral disc (IVD) is directly associated with the leading causes of disability in the industrialized world, neck and back pain. Current treatments focus on pain relief and mitigating symptoms rather than addressing the underlying source of pain, which in the majority of cases stems from radiculopathy. Strategies from tissue engineering have been introduced for the past 20 years to create biological treatments that can replace the pathologic tissue with a biomimetic implant that possesses regenerative potential. The current state of the field of IVD tissue engineering includes strategies for repair and replacement of individual components of the disc, the nucleus pulposus (NP) and annulus fibrosus (AF), but only a handful of technologies for total disc replacement (TDR) have shown promise for clinical translation in vitro and in vivo.

Total disc replacement with biological tissue-engineered IVDs (TE-IVDs) has only been tested in small animal models to date. This dissertation sought to address the need for a larger animal model that is clinically relevant to humans by demonstrating the feasibility of the canine cervical spine as a pre-clinical model of TDR with TE-IVDs. In this work, the focus was to investigate the appropriate implantation conditions for TDR in the cervical spine and the ability of TE-IVDs to integrate host tissue, mature, and restore function in vivo (Chapter 2). TE-IVDs for the canine cervical spine were developed as composite structures made of cell-seeded alginate NP surrounded by circumferentially aligned cell-seeded collagen AF. This in vivo study was the first to demonstrate that stably implanted TE-IVDs produced integrated tissues that resemble native IVD structure with viable cells in a canine pre-clinical model of TDR.

Despite the favorable outcomes in stably implanted TE-IVDs, new challenges were identified in the canine model that had not been encountered in rodents before. Segment instability caused 50% of TE-IVDs to displace out of the disc space upon implantation and scaled-up TEIVDs had yet to match native-like properties pre-operatively. The instability issue was addressed (chapter 3) by investigating a combined treatment approach of TE-IVD implantation with a resorbable plating system proposed to assist in transferring compressive loads of motion segments along the vertebral bodies and retain TE-IVD implants in the disc space. To improve potential functionality of TE-IVDs, the study described in chapter 4 leverages the tunable AF region of the TE-IVDs to investigate the potential of high-density collagen as AF scaffolds and assess the effects of initial scaffold concentration and cell seeding density with hMSCs on the remodeling of the resultant composite TE-IVD structure. Collectively, these studies offered promising alternatives to promote the success of TDR in a pre-clinical animal model with TE-IVDs.