Latest advances: Improving the anti-inflammatory and immunomodulatory properties of PEEK materials.

Excellent biocompatibility, mechanical properties, chemical stability, and elastic modulus close to bone tissue make polyetheretherketone (PEEK) a promising orthopedic implant material. However, biological inertness has hindered the clinical applications of PEEK. The immune responses and inflammatory reactions after implantation would interfere with the osteogenic process. Eventually, the proliferation of fibrous tissue and the formation of fibrous capsules would result in a loose connection between PEEK and bone, leading to implantation failure. Previous studies focused on improving the osteogenic properties and antibacterial ability of PEEK with various modification techniques. However, few studies have been conducted on the immunomodulatory capacity of PEEK. New clinical applications and advances in processing technology, research, and reports on the immunomodulatory capacity of PEEK have received increasing attention in recent years. Researchers have designed numerous modification techniques, including drug delivery systems, surface chemical modifications, and surface porous treatments, to modulate the post-implantation immune response to address the regulatory factors of the mechanism. These studies provide essential ideas and technical preconditions for the development and research of the next generation of PEEK biological implant materials. This paper summarizes the mechanism by which the immune response after PEEK implantation leads to fibrous capsule formation; it also focuses on modification techniques to improve the anti-inflammatory and immunomodulatory abilities of PEEK. We also discuss the limitations of the existing modification techniques and present the corresponding future perspectives.

Pathogenesis and therapeutic implications of matrix metalloproteinases in intervertebral disc degeneration: A comprehensive review.

Intervertebral disc (IVD) degeneration (IDD) is a common disorder that affects the spine and is a major cause of lower back pain (LBP). The extracellular matrix (ECM) is the structural foundation of the biomechanical properties of IVD, and its degradation is the main pathological characteristic of IDD. Matrix metalloproteinases (MMPs) are a group of endopeptidases that play an important role in the degradation and remodeling of the ECM. Several recent studies have shown that the expression and activity of many MMP subgroups are significantly upregulated in degenerated IVD tissue. This upregulation of MMPs results in an imbalance of ECM anabolism and catabolism, leading to the degradation of the ECM and the development of IDD. Therefore, the regulation of MMP expression is a potential therapeutic target for the treatment of IDD. Recent research has focused on identifying the mechanisms by which MMPs cause ECM degradation and promote IDD, as well as on developing therapies that target MMPs. In summary, MMP dysregulation is a crucial factor in the development of IDD, and a deeper understanding of the mechanisms involved is needed to develop effective biological therapies that target MMPs to treat IDD.

ROS-responsive magnesium-containing microspheres for antioxidative treatment of intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is a degenerative disease characterized by lower-back pain, causing disability globally. Antioxidant therapy is currently considered one of the most promising strategies for IVDD treatment, given the crucial role of reactive oxygen species (ROS) in IVDD pathogenesis. Herein, a ROS-responsive magnesium-containing microsphere (Mg@PLPE MS) was constructed for the antioxidative treatment of IVDD. The Mg@PLPE MS has a core-shell structure comprising poly(lactic-co-glycolic acid) (PLGA) and ROS-responsive polymer poly(PBT-co-EGDM) as the shell and a magnesium microparticle as the core. The poly(PBT-co-EGDM) can be destroyed by H2O2 through the H2O2-triggered hydrophobic-to-hydrophilic transition, subsequently promoting an Mg-water reaction to produce H2. Thus, Mg@PLPE MS provides a valuable platform for H2O2 elimination and controlled H2 release. The generated H2 scavenge for ROS by reacting with noxious •OH. Notably, the Mg@PLPE MS exerted significant antioxidative and anti-inflammatory effects in a disc degeneration rat model and alleviated extracellular matrix degradation and disc cells apoptosis, thereby underlining its efficacy in IVDD treatment. The Mg@PLPE MS also exhibited robust biocompatibility and negligible toxicity, presenting the promise for the antioxidative treatment of IVDD in vivo. STATEMENT OF SIGNIFICANCE: Antioxidant therapy is currently considered one of the most promising strategies for intervertebral disc degeneration (IVDD) treatment, given the crucial role of reactive oxygen species (ROS) in IVDD pathogenesis. Here, ROS-responsive magnesium-containing microspheres (Mg@PLPE MSs) were constructed to alleviate IVDD through controlled release of hydrogen gas. The Mg@PLPE MSs can effectively scavenge overproduced ROS by simultaneously reacting with H2O2 and •OH, thus creating a suitable microenvironment for inhibition of ECM degradation. As a result, Mg@PLPE MSs treated IVDD rats exhibit minimal nucleus pulposus decrease, less extracellular matrix degradation, minimal radial fissure of fibrous rings, and higher disc height index. Therefore, the as-prepared Mg@PLPE MSs may shed a new light on clinical treatment of IVDD.

Unraveling the mechanisms of intervertebral disc degeneration: an exploration of the p38 MAPK signaling pathway.

Intervertebral disc (IVD) degeneration (IDD) is a worldwide spinal degenerative disease. Low back pain (LBP) is frequently caused by a variety of conditions brought on by IDD, including IVD herniation and spinal stenosis, etc. These conditions bring substantial physical and psychological pressure and economic burden to patients. IDD is closely tied with the structural or functional changes of the IVD tissue and can be caused by various complex factors like senescence, genetics, and trauma. The IVD dysfunction and structural changes can result from extracellular matrix (ECM) degradation, differentiation, inflammation, oxidative stress, mechanical stress, and senescence of IVD cells. At present, the treatment of IDD is basically to alleviate the symptoms, but not from the pathophysiological changes of IVD. Interestingly, the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway is involved in many processes of IDD, including inflammation, ECM degradation, apoptosis, senescence, proliferation, oxidative stress, and autophagy. These activities in degenerated IVD tissue are closely relevant to the development trend of IDD. Hence, the p38 MAPK signaling pathway may be a fitting curative target for IDD. In order to better understand the pathophysiological alterations of the intervertebral disc tissue during IDD and offer potential paths for targeted treatments for intervertebral disc degeneration, this article reviews the purpose of the p38 MAPK signaling pathway in IDD.

Animal Models for Postoperative Implant-Related Spinal Infection.

Postoperative infections following implant-related spinal surgery are severe and disastrous complications for both orthopaedic surgeons and patients worldwide. They can cause neurological damage, disability, and death. To better understand the mechanism of these destructive complications and intervene in the process, further research is needed. Therefore, there is an urgent need for efficient, accurate, and easily available animal models to study the pathogenesis of spinal infections and develop new and effective anti-bacterial methods. In this paper, we provide a general review of the commonly used animal models of postoperative implant-related spinal infections, describe their advantages and disadvantages, and highlight the significance of correctly choosing the model according to the infection aspect under investigation. These models are valuable tools contributing to the better understanding of postoperative spinal infections and will continue to facilitate the invention of novel preventative and treatment strategies for patients with postoperative spinal infections. However, although they are valid and reproducible in some respects, the current animal models present certain limitations. Future ideal spinal infection animal models may assess the bacterial load of the same animal in real-time in vivo, and better mimic the human anatomy as well as surgical techniques. Strains other than Staphylococcus aureus account for a large proportion of postoperative spinal infections, and thus, the establishment of models to evaluate other types of microbial infections is expected in the future. Furthermore, novel transgenic models established on advancements in genome editing are also likely to be developed in the future.

Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) causes a variety of signs and symptoms, such as low back pain (LBP), intervertebral disc herniation, and spinal stenosis, which contribute to high social and economic costs. IDD results from many factors, including genetic factors, aging, mechanical injury, malnutrition, and so on. The pathological changes of IDD are mainly composed of the senescence and apoptosis of nucleus pulposus cells (NPCs), the progressive degeneration of extracellular matrix (ECM), the fibrosis of annulus fibrosus (AF), and the inflammatory response. At present, IDD can be treated by conservative treatment and surgical treatment based on patients' symptoms. However, all of these can only release the pain but cannot reverse IDD and reconstruct the mechanical function of the spine. The latest research is moving towards the field of biotherapy. Mesenchymal stem cells (MSCs) are regard as the potential therapy of IDD because of their ability to self-renew and differentiate into a variety of tissues. Moreover, the non-coding RNAs (ncRNAs) are found to regulate many vital processes in IDD. There have been many successes in the in vitro and animal studies of using biotherapy to treat IDD, but how to transform the experimental data to real therapy which can apply to humans is still a challenge. This article mainly reviews the treatment strategies and research progress of IDD and indicates that there are many problems that need to be solved if the new biotherapy is to be applied to clinical treatment of IDD. This will provide reference and guidance for clinical treatment and research direction of IDD.

The role of IL-1ß and TNF-α in intervertebral disc degeneration.

Low back pain (LBP), a prevalent and costly disease around the world, is predominantly caused by intervertebral disc (IVD) degeneration (IDD). LBP also presents a substantial burden to public health and the economy. IDD is mainly caused by aging, trauma, genetic susceptibility, and other factors. It is closely associated with changes in tissue structure and function, including progressive destruction of the extracellular matrix (ECM), enhanced senescence, disc cell death, and impairment of tissue biomechanical function. The inflammatory process, exacerbated by cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), are considered to be the key mediators of IDD and LBP. IL-1ß and TNF-α are the most important proinflammatory cytokines, as they have powerful proinflammatory activities and can promote the secretion of a variety of proinflammatory mediators. They are also upregulated in the degenerative IVDs, and they are closely related to various pathological IDD processes, including inflammatory response, matrix destruction, cellular senescence, autophagy, apoptosis, pyroptosis, and proliferation. Therefore, anti-IL-1ß and anti-TNF-α therapies may have the potential to alleviate disc degeneration and LBP. In this paper, we reviewed the expression pattern and signal transduction pathways of IL-1ß and TNF-α, and we primarily focused on their similar and different roles in IDD. Because IL-1ß and TNF-α inhibition have the potential to alleviate IDD, an in-depth understanding of the role of IL-1ß and TNF-α in IDD will benefit the development of new treatment methods for disc degeneration with IL-1ß and TNF-α at the core.