Mechanisms and therapeutic strategies for senescence-associated secretory phenotype in the intervertebral disc degeneration microenvironment.

As a permanent state of cell cycle arrest, cellular senescence has become an important factor in aging and age-related diseases. As a central regulator of physiology and pathology associated with cellular senescence, the senescence associated secretory phenotype can create an inflammatory and catabolic environment through autocrine and paracrine ways, ultimately affecting tissue microstructure. As an age-related disease, the correlation between intervertebral disc degeneration and cellular senescence has been confirmed by many studies. Various pathological factors in the microenvironment of intervertebral disc degeneration promote senescent cells to produce and accumulate and express excessive senescence associated secretory phenotype. In this case, senescence associated secretory phenotype has received considerable attention as a potential target for delaying or treating disc degeneration. Therefore, we reviewed the latest research progress of senescence associated secretory phenotype, related regulatory mechanisms and intervertebral disc cell senescence treatment strategies. It is expected that further understanding of the underlying mechanism between cellular senescence pathology and intervertebral disc degeneration will help to formulate reasonable senescence regulation strategies, so as to achieve ideal therapeutic effects. The translational potential of this article: Existing treatment strategies often fall short in addressing the challenge of repairing intervertebral disc Intervertebral disc degeneration（IVD） degeneration. The accumulation of senescent cells and the continuous release of senescence-associated secretory phenotype (SASP) perpetually impede disc homeostasis and hinder tissue regeneration. This impairment in repair capability presents a significant obstacle to the practical clinical implementation of strategies for intervertebral disc degeneration. As a result, we present a comprehensive overview of the latest advancements in research, the associated regulatory mechanisms, and strategies for treating SASP in IVD cells. This article aims to investigate effective interventions for delaying the onset and progression of age-related intervertebral disc degeneration. In an era where the aging population is becoming increasingly prominent, this endeavor holds paramount practical and translational significance.

Cortical Endplate Bone Density Measured by Novel Phantomless Quantitative Computed Tomography May Predict Cage Subsidence more Conveniently and Accurately.

OBJECTIVE: Previous studies have shown that bone mineral density (BMD) is a predictor of cage subsidence. Phantom-less quantitative computed tomography (PL-QCT) can measure volumetric bone mineral density (vBMD) of lumbar trabecular and cortical bone. The study of endplate vBMD (EP-vBMD) is important in predicting cage settlement after extreme lateral interbody fusion (XLIF). This study aimed to determine the risk factors for postoperative cage subsidence after XLIF, particularly focusing on the relationship between vBMD measured by automatic PL-QCT and cage subsidence. METHODS: Patients who underwent XLIF surgery from January 2018 to October 2020 with a minimum of 6 months of follow-up were retrospectively included. Cage subsidence was defined as >2 mm cage sinking on the adjacent endplate in follow-up imaging evaluation. Outcome measures were localized vBMDs included EP-vBMDs with different region of interest (ROI) heights measured by PL-QCT based on a customized muscle-fat algorithm. Shapiro-Wilk test, one-way ANOVA, Mann-Whitney test, Fisher exact test, univariable and multivariable logistic regression and receiver operating characteristic (ROC) curve analysis were executed in this study. RESULTS: One hundred and thirteen levels of 78 patients were included in the analysis. The mean age was 65 ± 7.9 years for 11 males and 67 females. Cage subsidence occurred on 45 (39.8%) surgical levels. There was no significant difference in demographics, fused levels, or preoperative radiographic parameters. 1.25-mm EP-vBMD (0.991 [0.985,0.997], p = 0.004) and P-TB-vBMD (cage-positioned trabecular volumetric bone mineral density) (0.988 [0.977-0.999], p = 0.026) were cage-subsidence relevant according to univariate analysis. Low 1.25-mm EP-vBMD (0.992 [0.985, 0.999], p = 0.029) was an independent risk factor according to multifactorial analysis. CONCLUSION: Preoperative low EP-vBMD was an independent risk factor for postoperative cage subsidence after XLIF. EP-vBMD measured by most cortex-occupied ROI may be the optimal vBMD parameter for cage subsidence prediction.

Biomechanical effects of screws of different materials on vertebra-pediculoplasty: a finite element study.

Background: The effects of cannulated screws made of polyetheretherketone (PEEK) on the biomechanical properties of the vertebral body during vertebra-pediculoplasty remain unclear. This study aimed to investigate whether PEEK screws have the potential to replace titanium alloy screws. Methods: The surgical model of two different materials of screws was constructed using the finite element method. The biomechanical effects of the two models on the vertebral body under different working conditions were compared. Results: ① The peak von Mises stress of PEEK screws was significantly lower than that of titanium screws, with a reduction ranging from 52% to 80%. ② The von Mises stress values for the injured T12 spine were similar for both materials. Additionally, the segmental range of motion and intervertebral disc pressure showed no significant difference between the two materials. Conclusion: PEEK screws demonstrated advantages over titanium screws and may serve as a viable alternative for screw materials in vertebra-pediculoplasty.

Advances in Therapeutic Applications of Extracellular Vesicles.

Extracellular vesicles (EVs) are nanoscale bilayer phospholipid membrane vesicles released by cells. Contained large molecules such as nucleic acid, protein, and lipid, EVs are an integral part of cell communication. The contents of EVs vary based on the cell source and play an important role in both pathological and physiological conditions. EVs can be used as drugs or targets in disease treatment, and changes in the contents of EVs can indicate the progression of diseases. In recent years, with the continuous exploration of the structure, characteristics, and functions of EVs, the potential of engineered EVs for drug delivery and therapy being constantly explored. This review provides a brief overview of the structure, characteristics and functions of EVs, summarizes the advanced application of EVs and outlook on the prospect of it. It is our hope that this review will increase understanding of the current development of medical applications of EVs and help us overcome future challenges.

[Research status of acetabular reconstruction in Crowe type â ¡ and â ¢ developmental dysplasia of the hip].

Developmental dysplasia of the hip (DDH) is a major cause of hip arthritis and ultimately total hip arthroplasty. Due to the dysplastic acetabulum, how to place the acetabular cup becomes a challenge in acetabular reconstruction for such patients. Especially in the acetabula classified as Crowe typeⅡand type Ⅲ, the dislocation of the femoral head causes bone defects above the true acetabulum, which will affect the stability of the acetabular cup when the acetabular reconstruction is performed at the true acetabulum. Many acetabular reconstruction methods such as bone grafting, the use of small acetabular cups, socket medialization technique, and high hip center technique are used to increase the host bone coverage of the cup. However, each method has its own shortcomings that can not be ignored so that there is no unified conclusion on the acetabular reconstruction methods for Crowe typeⅡand type Ⅲ hip dysplasia. This article summarized and evaluated various reconstruction methods in combination with the acetabular morphology of DDH, and put forward the research direction in the future.

Intervertebral Disk Degeneration: The Microenvironment and Tissue Engineering Strategies.

Intervertebral disk degeneration (IVDD) is a leading cause of disability. The degeneration is inevitable, and the mechanisms are complex. Current therapeutic strategies mainly focus on the relief of symptoms, not the intrinsic regeneration of the intervertebral disk (IVD). Tissue engineering is a promising strategy for IVDD due to its ability to restore a healthy microenvironment and promote IVD regeneration. This review briefly summarizes the IVD anatomy and composition and then sets out elements of the microenvironment and the interactions. We rationalized different scaffolds based on tissue engineering strategies used recently. To fulfill the complete restoration of a healthy IVD microenvironment, we propose that various tissue engineering strategies should be combined and customized to create personalized therapeutic strategies for each individual.

The Immuno-Modulation Effect of Macrophage-Derived Extracellular Vesicles in Chronic Inflammatory Diseases.

As natural nanocarriers and intercellular messengers, extracellular vesicles (EVs) control communication among cells. Under physiological and pathological conditions, EVs deliver generic information including proteins and nucleic acids to recipient cells and exert regulatory effects. Macrophages help mediate immune responses, and macrophage-derived EVs may play immunomodulatory roles in the progression of chronic inflammatory diseases. Furthermore, EVs derived from various macrophage phenotypes have different biological functions. In this review, we describe the pathophysiological significance of macrophage-derived extracellular vesicles in the development of chronic inflammatory diseases, including diabetes, cancer, cardiovascular disease, pulmonary disease, and gastrointestinal disease, and the potential applications of these EVs.

Segmental uncoverage ratio analysis of Crowe type-IV developmental dysplasia of the hip via 3-dimensional implantation simulation.

BACKGROUND: To study the segmental uncoverage ratio (UCR) of a 44-mm cup model placed in a true acetabulum of Crowe type-IV developmental dysplasia of the hip via 3-Dimensional (3D) implantation simulation. METHODS: Qualified CT imaging data of 26 patients (involving 30 hips) with Crowe type-IV DDH were imported into Mimics software for reconstruction. Then a 44-mm eggshell cup model was placed in a true acetabulum. First, total uncoverage ratio (TUCR) was measured. Then the virtual cup was divided into 4 segments according to the quadrant setting of the true acetabulum, i.e., anterior-superior (A-S) segment, anterior-inferior (A-I) segment, posterior-superior (P-S) segment and posterior-inferior (P-I) segment. The UCRs of the aforementioned segments were measured, i.e., anterior-superior uncoverage ratio (A-SUCR), anterior-inferior uncoverage ratio (A-IUCR), posterior-superior uncoverage ratio (P-SUCR) and posterior-inferior uncoverage ratio (P-IUCR). The acetabular height and anterior-posterior diameter on the 3-D model were also calculated. Statistic analyses were performed by using SPSS software package. RESULTS: TUCR was 0.2958 ± 0.1003 (95% [CI], 0.1020 to 0.5400) in this cohort of Crowe Type-IV hips. P-SUCR had the greatest value among all the segmental UCRs (0.1012 ± 0.0435, 95% confidence interval [CI],0.0152 to 0.1914) and the most significant positive correlation with TUCR (Pearson correlation = 0.889, p < 0.01. Linear regression R2 = 0.791). Similarly, P-IUCR and A-SUCR showed a significant positive correlation with TUCR. However, A-IUCR exhibited no correlation with either total or other segmental UCRs. P-SUCR was found to bear significant positive correlation with P-IUCR (pearson correlation = 0.644, p < 0.01. Linear regression R2 = 0.415). Acetabular height and A-P diameter were not correlated with TUCR. CONCLUSION: Implantation of a 44-mm cup into Crowe type IV acetabulum is feasible and could achieve acceptable host bone coverage in most of the cases. P-SUCR contributed most to TUCR. TUCR had no linear relationship with the size of the host acetabulum, suggesting that the pre-operative plan should be individualized.