Strategies for Annulus Fibrosus Regeneration: From Biological Therapies to Tissue Engineering

Intervertebral disc (IVD) is an avascular tissue which contributes to the weight bearing, motion, and flexibility of spine. However, IVD is susceptible to damage and even failure due to injury, pathology, and aging. Annulus fibrosus (AF), the structural and functional integrity of which is critically essential to confine nucleus pulpous (NP) and maintain physiological intradiscal pressure under mechanical loading, plays a critical role in the biomechanical properties of IVD. AF degeneration commonly results in substantial deterioration of IVD. During this process, the biomechanical properties of AF and the balance between anabolism and catabolism in IVD are progressively disrupted, leading to chronic back pain, and even disability of individuals. Therefore, repairing and regenerating AF are effective treatments to degeneration-associated pains. However, they remain highly challenging due to the complexity of natural AF tissue in the aspects of cell phenotype, biochemical composition, microstructure, and mechanical properties. Tissue engineering (TE), by combining biological science and materials engineering, shed lights on AF regeneration. In this article, we review recent advances in the pro-anabolic approaches in the form of cell delivery, bioactive factors delivery, gene therapy, and TE strategies for achieving AF regeneration

A computational model for investigating the effects of changes in bioavailability of insulin-like growth factor-1 on the homeostasis of the intervertebral disc

Insulin-like growth factor-1 (IGF-1) is well-known for upregulating cell proliferation and biosynthesis of the extracellular matrix in the intervertebral disc (IVD). Pathological conditions, such as obesity or chronic kidney disease cause IGF-1 deficiency in plasma. How this deficiency impacts disc homeostasis remains unknown. Pro-anabolic approaches for the treatment of disc degeneration based on enhancing IGF-1 bioavailability to tissue-cells are considered, but knowledge of their effectiveness in enhancing cellular anabolism of a degenerated disc is limited. In this study, we developed a computational model for disc homeostasis specifically addressing the role of IGF-1 in modulating both extracellular matrix biosynthesis and cellularity in the IVD. This model was applied to investigate how changes in IGF-1 bioavailability, namely deficiency or enhancement of growth factor, affect disc health. In this study, it was found that IGF-1 deficiency mainly affects the biosynthesis of ECM components, especially in the most external regions of the IVD such as the cartilage endplates and the outer portion of annulus fibrosus. Also, a total of three approaches for increasing IGF-1 bioavailability as a therapy for degenerated IVDs were investigated. It was found that all these strategies are only beneficial to those disc regions receiving sufficient nutritional supply (i.e., the outmost IVD regions), while they exacerbate tissue degradation in malnourished regions (i.e., inner portion of the disc). This suggests that pro-anabolic growth factor-based therapies are limited in that their success strongly depends on an adequate nutritional supply to the IVD tissue, which is not guaranteed in degenerated discs. •Low levels of IGF-1 in plasma decreases cellular anabolism in IVD.•Impaired nutritional supply to the disc decreases both cellular anabolism and viability.•Pro-anabolic treatments for IVD degeneration based on enhancing IGF-1 bioavailability must include delivery of nutrients to disc cells