Tissue-Engineered Annulus Fibrosus Repair and Nucleus Pulposus Augmentation in Pre-Clinical Models of Intervertebral Disc Degeneration

396 pagesIntervertebral discs (IVDs) are the cartilaginous structures in the spine that connect adjacent vertebrae, absorb shock from daily activities, and allow for articulation of the spine. Unfortunately, IVDs are prone to degeneration and have little to no capacity for self-repair. IVD degeneration is estimated to affect more than 90% of individuals throughout their lifetime, leading to lower back pain, disability and a low quality of life. Early stage degeneration is characterized by lesions in the annulus fibrosus (AF), the outer fibrous ring of the IVD, which allow nucleus pulposus (NP), the gelatinous core, to herniate and impinge on surrounding neurological structures. Current surgical treatment options are unable to effectively repair the IVD, leading to further degeneration and reherniation. This work aims to develop and translate tissue-engineered repair strategies with the long-term goal to treat patients with IVD herniations and prevent further degeneration. To bring tissue-engineered repair strategies to the clinic, it is imperative to understand what has already been investigated, what biomaterials and strategies are successful, and what challenges remain (Chapter 1). Individually, NP and AF repair strategies have been well-studied using a wide variety of biomaterials, biomolecules and cells; however, the IVD is a composite structure and therefore requires a composite repair strategy. Combined NP augmentation and AF repair strategies was first investigated in the rat-tail spine to restore IVD hydration and mechanical function ex vivo (Chapter 2). The combined repair strategy was then investigated in vivo in the sheep lumbar spine to prevent degeneration and maintain native hydration, morphology, and mechanical function over a six-week period (Chapter 3). While the biomaterials in both Chapters 2 and 3 were effective and showed positive results, they could still be optimized for improved performance. Mesenchymal stem cells were introduced into the AF repair strategy in order to improve the speed and quality of AF repair in vivo (Chapter 4). Chondroitinase ABC was investigated ex vivo as a pretreatment to improve adhesion of the AF repair strategy to native tissue (Chapter 5). Lastly, Fourier transform infrared microscopy was utilized to quantitatively analyze the local biochemical composition of healthy and degenerated IVDs (Chapter 6)