A ROS-responsive microsphere capsule encapsulated with NADPH oxidase 4 inhibitor ameliorates macrophage inflammation and ferroptosis.

Inflammatory macrophages within the synovium play a pivotal role in the progression of arthritis inflammation. Effective drug therapy targeting inflammatory macrophages has long been a goal for clinicians and researchers. The standard approach for treating osteoarthritis (OA) involves systemic treatment and local injection. However, the high incidence of side effects associated with long-term drug administration increases the risk of complications in patients. Additionally, the rapid clearance of the joint cavity poses a biological barrier to the therapeutic effect. NADPH oxidase 4 (NOX4) is an enzyme protein regulating the cellular redox state by generating reactive oxygen species (ROS) within the cell. In this study, we designed and fabricated a hydrogel microsphere consisting of methyl methacrylate (MMA) and polyvinyl acetate (PVA) as the outer layer structure. We then loaded GLX351322 (GLX), a novel selective NOX4 inhibitor, into hydrogel microspheres through self-assembly with the compound polyethylene glycol ketone mercaptan (mPEG-TK) containing a disulfide bond, forming nanoparticles (mPEG-TK-GLX), thus creating a two-layer drug-loaded microspheres capsule with ROS-responsive and slow-releasing capabilities. Our results demonstrate that mPEG-TK-GLX@PVA-MMA effectively suppressed TBHP-induced inflammation, ROS production, and ferroptosis, indicating a promising curative strategy for OA and other inflammatory diseases in the future.

GLX351322, a Novel NADPH Oxidase 4 Inhibitor, Attenuates TMJ Osteoarthritis by Inhibiting the ROS/MAPK/NF-κB Signaling Pathways.

As a degenerative disease in joints, temporomandibular joint osteoarthritis (TMJOA) is characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic synovitis, severely undermining functions and quality of life in patients. NADPH oxidase 4 (NOX4) contributes to reactive oxygen species (ROS) production and inflammatory pathway activation in osteoarthritis, which has attracted increasing attention in research in recent years. GLX351322 (GLX), a novel NOX4 inhibitor, exerts a protective effect on chondrocytes. However, whether it has a therapeutic effect on ROS production and inflammatory responses in synovial macrophages remains to be evaluated. In this study, we examined the effect of GLX on LPS-induced ROS production and inflammatory responses in vitro and on complete Freund's adjuvant (CFA)-induced TMJ inflammation in vivo. We found that GLX could depress LPS-induced intracellular ROS production and inflammatory response without cytotoxicity by inhibiting the ROS/MAPK/NF-κB signaling pathways. In line with in vitro observations, GLX markedly attenuated the synovial inflammatory reaction in the TMJ, thus protecting the condylar structure from severe damage. Taken together, our results suggest that GLX intervention or NOX4 inhibition is a promising curative strategy for TMJOA and other inflammatory diseases.

Radiologic outcomes of temporomandibular joint disk repositioning by suturing through an open incision in adolescent patients with anterior disk displacement.

PURPOSE: To investigate the efficacy and stability of temporomandibular joint disk repositioning by suturing through an open incision in adolescents with anterior disk displacement (ADD). METHODS: Patients (aged 10-18 years) diagnosed with ADD and operated for disc repositioning between June 2019 and January 2021 were included in this study. Magnetic resonance imaging (MRI) and cephalometric films before and 1 year after surgery were collected from all patients. The surgical success rate was defined as the primary outcome variable. Changes of condylar height, mandibular asymmetry, and retrognathia were defined as the secondary outcome variables. RESULTS: One hundred and four patients (167 joints) with a mean age of 14.6 ± 1.81 years were included in this study. Postoperative MRIs showed that all disks had been repositioned with an overall success rate of 94%. Statistically significant differences were found in the improvement of condylar height (P < .001), mandibular asymmetry (P < .001), and retrognathia (P < .001) after 1 year of follow-up. The relapse rate in patients <15 years (8.57%) was higher than that of patients older than 15 years (4.12%), although this was not statistically significant (P = .387). CONCLUSIONS: For juvenile patients, disk repositioning by suturing through an open incision was an effective treatment. Early surgery can promote condylar regeneration and alleviate maxillofacial deformity in juvenile patients.

[Influence of bilateral coronoidectomy on temporomandibular joint stress distribution after costochondral graft reconstruction: a finite element analysis].

PURPOSE: To explore the effect of bilateral coronoidectomy on stress distribution after reconstruction of temporomandibular joint (TMJ) by costochondral graft. METHODS: Ten groups of models were established to simulate costochondral graft reconstruction with simultaneously different distances (0, 2, 4, 6, 8 mm) of mandibular advancement, with or without coronoidectomy. Force and stress distribution in the rib-cartilage area were analyzed by finite element analysis. RESULTS: In the process of bilateral joint reconstruction with simultaneously mandible advancement ranging from 0 mm to 8 mm, when the coronoid processes were retained, the forward deformation of the cartilage occurred and the shear force decreased in turn, from 113.2 N to 26.7 N on the left side and from 133.7 N to 1.9 N on the right side. When the coronoid processes were removed, the cartilage deformed backward and the shear force increased successively, from 94.6 N to 188.5 N on the left and 70.1 N to 157.7 N on the right. The stress in the neck was obviously concentrated when mandible advanced 8 mm. CONCLUSIONS: Coronoidectomy has an important impact on stress distribution in the TMJ area, and keeping the coronoid process is beneficial to maintain the mechanical balance. Bilateral CCG reconstruction with coronoidectomy for lengthy mandible advancement (≥ 8 mm) may lead to prominent increase in shear force beyond CCG resistance, resulting in a costal-cartilage junction fracture.

Biomechanical analysis of costochondral graft fracture in temporomandibular joint replacement.

This study is the first attempt to explore the reason of costochondral graft fracture after lengthy mandible advancement and bilateral coronoidectomy by combining finite element analysis and mechanical test. Eleven groups of models were established to simulate costochondral graft reconstruction in different degrees of mandible advancement, ranging from 0 to 20 mm, in 2 mm increment. Force and stress distribution in the rib-cartilage area were analyzed by finite element analysis. Mechanical test was used to evaluate the resistance of the rib-cartilage complex. Results showed a sharp increase in horizontal force between 8 and 10 mm mandible advancement, from 26.7 to 196.7 N in the left side, and continue increased after 10 mm, which was beyond bone-cartilage junction resistance according to mechanical test. Therefore, we concluded that bilateral reconstruction with coronoidectomy for lengthy mandible advancement (≥ 10 mm) may lead to prominent increase in shear force and result in a costal-cartilage junction fracture, in this situation, alloplastic prosthesis could be a better choice. We also suggested that coronoidectomy should be carefully considered unless necessary.

Isorhamnetin 3-O-neohesperidoside promotes the resorption of crown-covered bone during tooth eruption by osteoclastogenesis.

Delayed resorption of crown-covered bone is a critical cause of delayed tooth eruption. Traditional herbal medicines may be good auxiliary treatments to promote the resorption of crown-covered bone. This study was carried out to analyse the effect of isorhamnetin 3-O-neohesperidoside on receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclastogenesis in vitro and resorption of the crown-covered bone of the lower first molars in mice in vivo. Isorhamnetin 3-O-neohesperidoside promoted osteoclastogenesis and the bone resorption of mouse bone marrow macrophages (BMMs) and upregulated mRNA expression of the osteoclast-specific genes cathepsin K (CTSK), vacuolar-type H + -ATPase d2(V-ATPase d2), tartrate resistant acid phosphatase (TRAP) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). NFATc1, p38 and AKT signalling was obviously activated by isorhamnetin 3-O-neohesperidoside in osteoclastogenesis. Isorhamnetin 3-O-neohesperidoside aggravated resorption of crown-covered bone in vivo. In brief, isorhamnetin 3-O-neohesperidoside might be a candidate adjuvant therapy for delayed intraosseous eruption.

Biomechanical evaluation of Chinese customized three-dimensionally printed total temporomandibular joint prostheses: A finite element analysis.

PURPOSE: This work aims to evaluate the biomechanical behavior of Chinese customized three-dimensional (3D)-printing total temporomandibular joint (TMJ) prostheses by means of finite element analysis. METHODS: A 3D model was established by Mimics 18.0, then output in a stereolithography (STL) format. Two models were established to investigate the strain behaviors of an intact mandible and a one-side implanted mandible respectively. Hypermesh and LS-DYNA software were used to establish computer-aided engineering finite element models. The stress distribution on the custom-made total TMJ prosthesis and the strain distribution on the mandible were analyzed by loading maximal masticatory force. RESULTS: The maximum stress on the surface of the ultra-high-molecular weight polyethylene was 19.61 MPa. With respect to the mandibular component, the maximum stress in the mandibular component was located at the anterior and posterior surface of the condylar neck, reaching 170.01 MPa. The peak von Mises stress was observed on the topside screw of the mandible, which was found to be 236.08 MPa. For the intact model, it was observed that the strain distribution was basically symmetrical. For the model with the prosthesis, the curve of strain distribution was fundamentally consistent with that in the intact mandible, except for the last 24 mm along the control line. A prominent strain decrease between 41.4% and 58.3% was observed in this area. CONCLUSIONS: Chinese customized 3D-printed total TMJ prostheses exhibit uniform stress distribution without changing the behavior of the opposite side natural joint. Furthermore, the prostheses have a great potential to be improved in design and materials with a promising future.

Characteristics of Chinese Costal Cartilage and Costa Calcification Using Dual-Energy Computed Tomography Imaging.

To assess characteristics of Chinese costal cartilage and costa calcification using Dual-Energy computed tomography(DECT). 154 patients who underwent chest DECT scanning were included in our study. They were divided into following groups: less than 30 years old, 31-40 years old, 41-50 years old, 51-60 years old and over 60 years old. The sixth, seventh and eighth costal cartilages and costas were evaluated. Calcification patterns of cartilage were classified as central(C), peripheral(P), mixed(M) and no calcification(N) types. Calcification degree of cartilage was distinguished as 1(0-25%), 2(26-50%) and 3(>50%). CT value, calcium and water concentrations were measured in costal cartilage, cortical or cancellous bone respectively. An increasing C pattern of cartilage was displayed in females, while P type preferred in males as age increased. Calcification degree generally changed from 1 to 2 or 3 in females. CT value and calcium concentration of cartilage went through a gradual rising course and peaked in their 40-50 years, while those two indices of cancellous bone decreased gradually since their 50 years in females. The findings suggest a gradual calcification of the costal cartilage took place before 40-50 years old and a sharp bone loss of the costa happened after 40-50 years old in females.

The fate of autogenous free fat grafts in the human temporomandibular joint using magnetic resonance imaging.

OBJECTIVE: Autologous fat grafts in the temporomandibular joint (TMJ) has achieved positive clinical effects in preventing adhesion after surgery. However it still remains indeterminate about the survival rate of grafted fat. The purpose of this study was to evaluate the long-term survival rate of free fat grafts in the TMJ using magnetic resonance imaging (MRI). MATERIALS AND METHODS: 89 patients (117 joints) with free fat grafts placed into TMJs following modified TMJ disc anchor were included in our study. They were divided into the following groups according to the time lapse between TMJ surgery and the latest MRI investigation: 1-3 months, 4-6 months, 7-12 months, 13-24 months, and >24 months. The signal intensity changes and volume retention were evaluated by MRI. RESULTS: The volume retention rate of grafted free fat showed that the size was hovering right around 50% although it reduced very slowly with a long-term follow-up. Nearly half joints showed lower signal intensity of the grafted fat on MRI within 6 months and it recovered to normal compared with that of the day after surgery 6 months later. CONCLUSIONS: Free fat grafted into TMJ cavity could be alive for a long time with the survival rate about 48.44%. However the survival mechanism has still been unknown, which need us to explore and study in the future.