Microvascular changes are considered key factors in the process of intervertebral disk degeneration (IDD). Microvascular invasion and growth into the nucleus pulposus (NP) and cartilaginous endplates are unfavorable factors that trigger IDD. In contrast, the rich distribution of microvessels in the bony endplates and outer layers of the annulus fibrosus is an important safeguard for the nutrient supply and metabolism of the intervertebral disk (IVD). In particular, the adequate supply of microvessels in the bony endplates is the main source of the nutritional supply for the entire IVD. Microvessels can affect the progression of IDD through a variety of pathways. Many studies have explored the effects of microvessel alterations in the NP, annulus fibrosus, cartilaginous endplates, and bony endplates on the local microenvironment through inflammation, apoptosis, and senescence. Studies also elucidated the important roles of microvessel alterations in the process of IDD, as well as conducted in-depth explorations of cytokines and biologics that can inhibit or promote the ingrowth of microvessels. Therefore, the present manuscript reviews the published literature on the effects of microvascular changes on IVD to summarize the roles of microvessels in IVD and elaborate on the mechanisms of action that promote or inhibit de novo microvessel formation in IVD.

Low back pain is a common chronic disease that can severely affect the patient\'s work and daily life. The breakdown of spinal mechanical homeostasis caused by intervertebral disc (IVD) degeneration is a leading cause of low back pain. Annulus fibrosus (AF), as the outer layer structure of the IVD, is often the first affected part. AF injury caused by consistent stress overload will further accelerate IVD degeneration. Therefore, regulating AF injury repair and remodeling should be the primary goal of the IVD repair strategy. Mechanical stimulation has been shown to promote AF regeneration and repair, but most studies only focus on the effect of single stress on AF, and lack realistic models and methods that can mimic the actual mechanical environment of AF. In this article, we review the effects of different types of stress stimulation on AF injury repair and remodeling, suggest possible beneficial load combinations, and explore the underlying molecular mechanisms. It will provide the theoretical basis for designing better tissue engineering therapy using mechanical factors to regulate AF injury repair and remodeling in the future.

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the spine, including lower back pain, with or without numbness and/or dysfunction in the lower extremities, disc herniation, spinal stenosis, and spondylolisthesis. Promising and established treatment modalities include repair of the annulus fibrosis, injection of expanded or nonexpanded autologous or allogenic cells that are chondrogenic or from a stem cell lineage used to promote matrix tissue regeneration of the intervertebral disc, including nucleus pulpous cells and mesenchymal stem cells isolated from bone marrow, umbilical cord blood, or adipose tissue; and injection of platelet-rich plasma, platelet-rich fibrin, or fibrin sealant. Early clinical studies show promise for pain reduction and functional recovery. LEVEL OF EVIDENCE: Level V, expert opinion.

Annulus fibrosus (AF) plays a crucial role in the biomechanical loading of intervertebral disc (IVD). AF is difficult to self-heal when the annulus tears develop, because AF has a unique intricate structure and biologic milieu in vivo. Tissue engineering is promising for repairing AF rupture, but construction of suitable mechanical matching devices or scaffolds is still a grand challenge. To deeply know the varied forces involved in the movement of the native annulus is highly beneficial for designing biomimetic scaffolds to recreate the AF function. In this review, we overview six freedom degrees of forces and adhesion strength on AF tissue. Then, we summarize the mechanical modalities to simulate related forces on AF and to assess the characteristics of biomaterials. We finally outline some current advanced techniques to develop mechanically adaptable biomaterials for AF rupture repair.

Back pain is an elusive symptom complicated by a variety of possible causes, precipitating and maintaining factors, and consequences. Notably, the underlying pathology remains unknown in a significant number of cases. Changes to the intervertebral disc (IVD) have been associated with back pain, leading many to postulate that the IVD may be a direct source of pain, typically referred to as discogenic back pain. Yet despite decades of research into the neuroanatomy of the IVD, there is a lack of consensus in the literature as to the distribution and function of neural elements within the tissue. The current scoping review provides a comprehensive systematic overview of studies that document the topography, morphology, and immunoreactivity of neural elements within the IVD in humans.
Articles were retrieved from six separate databases in a three-step systematic search and were independently evaluated by two reviewers.
Three categories of neural elements were described within the IVD: perivascular nerves, sensory nerves independent of blood vessels, and mechanoreceptors. Nerves were consistently localized within the outer layers of the annulus fibrosus. Neural ingrowth into the inner annulus fibrosus and nucleus pulposus was found to occur only in degenerative and disease states.
While the pattern of innervation within the IVD is clear, the specific topographic arrangement and function of neural elements in the context of back pain remains unclear.

In light of the correlation between chronic back pain and intervertebral disc (IVD) degeneration, this literature review seeks to illustrate the importance of the hydraulic response across the nucleus pulposus (NP)-annulus fibrosus (AF) interface, by synthesizing current information regarding injurious biomechanics of the spine, stemming from axial compression. Damage to vertebrae, endplates (EPs), the NP, and the AF, can all arise from axial compression, depending on the segment\'s posture, the manner in which it is loaded, and the physiological state of tissue. Therefore, this movement pattern was selected to illustrate the importance of the bracing effect of a pressurized NP on the AF, and how injuries interrupting support to the AF may contribute to IVD degeneration.

Intervertebral discs (IVDs) are often referred to as the largest avascular structures of the human body, yet a collective resource characterizing the vascularization of the IVD does not exist. To address this gap, the objective of this study was to conduct a comprehensive search of the literature to review and summarize current knowledge of the prevalence and localization of blood supply in human IVDs, with a scoping review. A comprehensive search of peer-reviewed publications on the topic of IVD vascularization in humans was conducted across six electronic databases: PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and BIOSIS Previews. Studies of humans were included regardless of age, sex, ethnicity, and health status, with the exception of IVD herniation. Two independent reviewers screened titles and abstracts and full-texts according to eligibility criteria. The review was conducted and reported according to Preferred Reporting Items for Systematic Reviews Extension for Scoping Reviews guidelines. Our search yielded 3122 articles, with 22 articles meeting the inclusion criteria. The study samples ranged in age from fetal to >90 years and included both sexes, various health statuses, and used different methodologies (eg, histology, medical imaging, and gross dissection) to assess vasculature. Overall, consistent observations were that (a) the nucleus pulposus of the IVD is avascular throughout life, (b) both the cartilage endplates and annulus fibrosus receive considerable blood supply early in life that diminishes over the lifespan, and (c) vascular ingrowth into the cartilage endplates and inner layers of the annulus fibrosus is commonly associated with damaged or disrupted tissue, irrespective of age. Histology and immunohistochemistry are often used to report vascularization of the IVD. The body of the current literature suggests that the IVD should not be generalized as an avascular tissue. Instead, vascularization of the IVD differs based on the constituent tissues, their age, and state of degeneration or damage.

The number of diabetic patients grows constantly worldwide. Many patients suffer simultaneously from diabetes mellitus type 2 (T2DM) and intervertebral disc disease (IVDD), suggesting a strong link between T2DM and IVDD. T2DM rodent models provide versatile tools to study this interrelation. We hypothesized that the previously achieved studies in rodents approved it. Performing a search in the publicly available electronic databases according to our inclusion (e.g., experimental study with clearly outlined methods investigating IVDD in diabetic rodent models) and exclusion (e.g., non-experimental) criteria, we included 23 studies from 1992 to 2020 analyzing different aspects of IVDD in diabetic rodents, such as on pathogenesis (e.g., effects of hyperglycemia on IVD cells, sirtuin (SIRT)1/p53 axis in the interrelation between T2DM and IVDD), risk factors (e.g., high content of advanced glycation end-products (AGEs) in modern diets), therapeutical approaches (e.g., insulin-like growth factor (IGF-I)), and prophylaxis. Regarding their quality, 12 studies were classified as high, six as moderate, and five as low. One strong, 18 moderate, and three mild evidences of the link between DM and IVDD in rodents were found, while only one study has not approved this link. We concluded that T2DM has a devastating effect on IVD, particularly in advanced cases, which needs to be further evaluated.

Introduction: Patients with lumbar disc herniation and associated sciatica are often referred for lumbar discectomy. The surgical defect in the annulus fibrosus is typically left unrepaired after lumbar discectomy. Patients with large postsurgical annular defects (≥6 mm width) have a higher risk of symptom recurrence and reoperation compared to those with small defects. In these high-risk patients, a treatment gap exists due to the lack of effective treatments for durable annulus fibrosus repair.Areas covered: This article highlights the therapeutic need and summarizes the clinical results of a bone-anchored annular closure device (Barricaid) that was designed to fill the treatment gap in patients with large postsurgical annular defects. Clinical results were summarized by means of a systematic review with meta-analysis of two randomized and two nonrandomized controlled studies.Expert opinion: Professional societal recommendations and clinical study results support the adoption of bone-anchored annular closure for use in properly selected patients undergoing lumbar discectomy who are at high-risk for reherniation due to a large postsurgical defect in the annulus fibrosus. The risks of symptomatic reherniation and reoperation are approximately 50% lower in patients treated with lumbar discectomy and the Barricaid device compared to lumbar discectomy only, representing a clinically effective treatment strategy.

Intervertebral disc research has sought to develop a deeper understanding of spine biomechanics, the complex relationship between disc health and back pain, and the mechanisms of spinal injury and repair. To do so, many researchers have focused on characterizing tissue-level properties of the disc, where the roles of tissue subcomponents can be more systematically investigated. Unfortunately, experimental challenges often limit the ability to measure important disc tissue- and subtissue-level behaviors, including fiber-matrix interactions, transient nutrient and electrolyte transport, and damage propagation. Numerous theoretical and numerical modeling frameworks have been introduced to explain, complement, guide, and optimize experimental research efforts. The synergy of experimental and computational work has significantly advanced the field, and these two aspects have continued to develop independently and jointly. Meanwhile, the relationship between experimental and computational work has become increasingly complex and interdependent. This has made it difficult to interpret and compare results between experimental and computational studies, as well as between solely computational studies. This paper seeks to explore issues of model translatability, robustness, and efficient study design, and to propose and motivate potential future directions for experimental, computational, and combined tissue-level investigations of the intervertebral disc.