Comparative study of normal condyle and temporomandibular joint prosthesis movement during mouth opening by dynamic magnetic resonance imaging and computed tomography.

Background: To analyze and compare the trajectory of condylar motion during mouth opening in normal volunteers and patients after total joint replacement (TJR) of the temporomandibular joint (TMJ). Methods: Condylar movement during mouth opening was recorded by dynamic magnetic resonance imaging (MRI) for volunteers with normal TMJs and dynamic computed tomography (CT) for patients after TMJ TJR. Trajectories of the points selected every 5 mm from the superior point of the condyle (P0) along its axis to the mandibular angle (P-25) were recorded. The arc length and curvature radius of average trajectories for each point were calculated and compared between the normal joints and TJRs, especially P-10 which is the corresponding point of the prosthesis apex without lateral pterygoid muscle (LPM) attachment at the normal joint with LPM attachment. The location of the point with the most similar trajectory was identified in the normal joints and compared with the condylar prosthesis. Results: A total of 9 volunteers with 18 normal TMJs, and 5 patients with 6 prostheses were included in this study. For normal TMJs, the average condylar trajectories during mouth opening were a concave upward curve. Meanwhile, the trajectories of contralateral normal joints in patients with unilateral TJR and all condylar prostheses were significantly decreased. The arc length and curvature radius of average trajectories gradually decreased from P0. In the normal joints, P-20 had the most similar trajectories with the average arc lengths and a curvature radius of 13.0/4.2 mm. In P-10, the average arc lengths and curvature radius of the normal cases, natural TMJ of the unilateral replacement patients, prosthetic TMJ of the unilateral replacement patients, and prosthetic TMJ of the bilateral replacement patient, were 15.6/6.6 mm, 13.1/4.9 mm, 4.7/4.4 mm, and 6.4/5.8 mm, respectively. Conclusions: P-20 in the normal joint exhibited the most similar trajectory among individuals. The trajectory difference between the prosthesis apex without LPM attachment and the corresponding point at the normal joint with LPM attachment provides a reference for fossa prosthesis functional surface design.

Intra-articular treatment of temporomandibular joint osteoarthritis by injecting actively-loaded meloxicam liposomes with dual-functions of anti-inflammation and lubrication.

Temporomandibular joint (TMJ) osteoarthritis is a common osteochondral degenerative disease which can severely affect patient's mouth opening and mastication. Meloxicam (MLX), one of the most widely used non-steroidal anti-inflammatory drugs, is the main clinical therapy for the treatment of TMJ osteoarthritis. However, the clinical effect is greatly compromised because of its poor water solubility and high lipophilicity. In the present study, we developed an actively-loaded liposomal formulation, namely MLX-Ca(AC)2Lipo, using meglumine to enhance aqueous solubility and divalent metal (Ca2+) solution to improve encapsulation efficiency. By the formation of the nano-bowl shaped MLX-Ca precipitates inside the liposomes, MLX-Ca(AC)2Lipo successfully achieved an optimal encapsulation efficiency as high as 98.4% compared with previous passive loading method (60.6%). Additionally, MLX-Ca(AC)2Lipo maintained stable, and the slow drug release not only prolonged the duration of drug efficacy but also improved bioavailability. It was shown in the in vitro and in vivo tests that MLX-Ca(AC)2Lipo downregulated the synthesis of the inflammatory factors (such as prostaglandin-E2) and as a consequence reduced chondrocytes apoptosis and extracellular matrix degeneration. Furthermore, the intra-articular injection of MLX-Ca(AC)2Lipo enhanced bioinspired lubrication of TMJ, protecting the cartilage from progressive wear. In summary, MLX-Ca(AC)2Lipo with dual-functions of anti-inflammation and lubrication is a promising nanomedicine for the treatment of TMJ osteoarthritis by intra-articular injection.

Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing.

Cytosine base editors (CBEs) efficiently generate precise C·G-to-T·A base conversions, but the activation-induced cytidine deaminase/apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (AID/APOBEC) protein family deaminase component induces considerable off-target effects and indels. To explore unnatural cytosine deaminases, we repurpose the adenine deaminase TadA-8e for cytosine conversion. The introduction of an N46L variant in TadA-8e eliminates its adenine deaminase activity and results in a TadA-8e-derived C-to-G base editor (Td-CGBE) capable of highly efficient and precise C·G-to-G·C editing. Through fusion with uracil glycosylase inhibitors and further introduction of additional variants, a series of Td-CBEs was obtained either with a high activity similar to that of BE4max or with higher precision compared to other reported accurate CBEs. Td-CGBE/Td-CBEs show very low indel effects and a background level of Cas9-dependent or Cas9-independent DNA/RNA off-target editing. Moreover, Td-CGBE/Td-CBEs are more efficient in generating accurate edits in homopolymeric cytosine sites in cells or mouse embryos, suggesting their accuracy and safety for gene therapy and other applications.

Heterotopic ossification after alloplastic temporomandibular joint replacement: a case cohort study.

BACKGROUND: Heterotopic ossification (HO) is one of the serious complications leading to the failure of alloplastic temporomandibular joint replacement (TJR). However, there was few research on its exact incidence and occurrence. Severe HO might result in pain and limited mouth opening after surgery. Therefore, it is necessary to clarify its clinical and imaging manifestations. The purpose of this study was to study the occurrence and classify HO after the alloplastic TJR. METHOD: Patients who underwent standard TJR (Zimmer Biomet stock prostheses or Chinese stock prostheses) with fat graft and at least 1-year-follow-up were included. HO was classified into 4 types according to postoperative computed tomography (CT) scans. Type and occurrence in different TMJ disease were compared. Joint space within 1 week after operation was measured and compared between HO and non-HO TJRs. Maximum incisal opening (MIO), pain, and quality of life (QoL) were recorded and their relevance with HO was analyzed statistically. RESULT: 81cases with 101 joints were included in the study. The mean follow-up time was 22.9 months (12 ~ 56 months). Among the 48 joints, 27 (56.3%) were type I (bone islands); 16 (33.3%) were type II (bone spurs from the mandibular ramus); 3 (6.3%) were type III (bone spurs from the fossa); and 2 (4.2%) were type IV (bone spurs from both the mandibular ramus and fossa). In HO patients, joint space in type IV was smaller than the other 3 types. Pain scores in HO were significantly greater than non-HO patients before and after operations (p < 0.05). 1 patient in Type IV HO developed ankylosis and had prosthesis revision which accounted for 2.1% in HO patients and 1.0% in all TJR patients. CONCLUSION: HO after alloplastic TJR with fat graft was not severe except for type IV, which was easy to cause ankylosis. Preserving sufficient TJR space was important for ankylosis prevention.

Biomechanical analysis of a temporomandibular joint prosthesis for lateral pterygoid muscle reattachment.

OBJECTIVE: To analyze the biomechanical properties of a novel temporomandibular joint (TMJ) prosthesis with an attachment area for the lateral pterygoid muscle (LPM). STUDY DESIGN: Three prosthesis models were created and compared using finite element analysis for the displacement, stress, and strain when simulating the maximum bite force loading. A verification experiment and a compression test were conducted. RESULTS: The displacement, stress, and strain of the novel TMJ prosthesis were larger than the solid condylar neck prosthesis and similar to the slotted condylar neck prosthesis, but the values were far less than the yield strength of titanium alloy. The maximum stress and strain in the novel TMJ prosthesis was concentrated in the inner and boundary areas of the LPM reattachment region beside the thinnest part of the prosthesis neck. The difference in the strain values measured using the verification test and those using finite element analysis was <20%. Compression testing of the novel TMJ prosthesis revealed that the mandible fractured when the force reached 588.97 N, whereas the prosthesis itself did not break or deform. CONCLUSIONS: The mechanical distribution of the novel prosthesis was feasible under maximum bite force for potential clinical application.