Mechanoresponsive regulation of tissue regeneration during distraction osteogenesis.

Distraction osteogenesis is widely used for bone tissue engineering. Mechanical stimulation plays a central role in the massive tissue regeneration observed during distraction osteogenesis. Although distraction osteogenesis has been a boon for patients with bone defects, we still have limited knowledge about the intrinsic mechanotransduction that converts physical forces into biochemical signals capable of inducing cell behavior changes and new tissue formation. In this review, we summarize the findings for mechanoresponsive factors, including cells, genes, and signaling pathways, during the distraction osteogenesis different phases. These elements function for coupling of osteogenesis and angiogenesis via the Integrin-FAK, TGF-ß/BMP, Wnt/ß-catenin, Hippo, MAPK, PI3K/Akt, and HIF-1α signaling pathways in a mechanoresponsive niche. The available evidence further suggests the existence of a balance between the epithelial-mesenchymal transition and mesenchymal-epithelial transition under hypoxic stress. We also briefly summarize the current in silico simulation algorithms and propose several future research directions that may advance understanding of distraction osteogenesis in the era of bioinformation, particularly the integration of artificial intelligence models with reliable single-cell RNA sequencing datasets. The objective of this review is to utilize established knowledge to further optimize existing distraction protocols and to identify potential therapeutic targets.

Assessment of the Correlation Between Types of Orbital Fractures and Ocular Symptoms, and the Effect of Manual Preformed and Patient-Specific Mesh Implants: A Retrospective Study.

OBJECTIVE: Although certain orbital fractures are associated with specific clinical symptoms, these relationships should be reviewed comprehensively. The optimal choice between manual preformed mesh implants (MPIs) and patient-specific mesh implants (PSIs) for orbital reconstruction remains undetermined due to inconclusive evidence regarding their effectiveness. METHODS: This retrospective study investigated 280 patients with unilateral orbital fractures to explore the correlation between clinical ocular symptoms, including diplopia, enophthalmos, limitation of ocular movement, blindness, and the specific type of orbital fracture. The effects on orbital volume (OV) and orbital volume ratio (OVR) of MPI and PSI with and without the use of navigation were also evaluated in this study. Patients were categorized into 4 groups: MPI, PSI, navigation-assisted MPI, and navigation-assisted PSI. After this categorization, alterations in OV and OVR were analyzed before and after surgical intervention. RESULTS: Significant correlations were observed between the orbital fracture type and diplopia, enophthalmos, and limitation of ocular movement (P < 0.05). Patients in the MPI group exhibited a notable difference in the postoperative OV between the injured and normal sides (P < 0.05), but no statistically significant difference was found in the postoperative OV between the injured and normal sides among the patients in the other 3 groups (P > 0.05). Moreover, the MPI group demonstrated significantly higher postoperative OVR than the other groups (P < 0.05). Notably, PSI remained effective with or without navigation, MPI combined with navigation technology achieved a reconstruction quality similar to that of PSI by rectifying positioning errors during surgery. CONCLUSION: The authors found significant correlations (P < 0.05) between orbital fracture type and diplopia, enophthalmos, and limitations of ocular movement. Patient-specific mesh implant plays an important role in orbital reconstruction. It is also a good method for reconstructing orbital fractures using MPI assisted by navigation technology.

CircRNA-23525 regulates osteogenic differentiation of adipose-derived mesenchymal stem cells via miR-30a-3p.

Adipose-derived mesenchymal stem cells (ADSCs) are considered to be seed cells in bone tissue engineering and emerging evidence indicates that circular RNAs (circRNAs) function in the osteogenic differentiation of ADSCs. The mechanisms of osteoblastic differentiation of ADSCs from the perspective of circRNA modulation are examined in this study. First, circRNA-23525 was upregulated during osteoblastic differentiation of ADSCs. Second, overexpression of circRNA-23525 increased Runx2, ALP and OCN at both mRNA and protein levels. Alkaline phosphatase (ALP) and Alizarin Red staining indicated a similar tendency. Silencing circRNA-23525 produced the opposite effect. Bioinformatics analysis with luciferase assays confirmed that circRNA-23525 functioned as a sponge for miR-30a-3p. In the osteoblastic differentiation of ADSCs, the dynamic expression of miR-30a-3p and circRNA-23525 resulted in an opposite trend at 3, 7 and 14 days. Overexpression of circRNA-23525 downregulated miR-30a-3p and knockdown of circRNA-23525 promoted the expression of miR-30a-3p. Bioinformatics methods and luciferase assays suggested that miR-30a-3p modulated Runx2 expression by targeting 3'UTR. Knockdown of miR-30a-3p facilitated osteogenesis in ADSCs and enhancing miR-30a-3p interfered with the osteogenic process. Finally, circRNA-23525 overexpression significantly increased Runx2 expression, while co-transfection of miR-30a-3p mimics reversed it. Runx2 expression was decreased in circRNA-23525-knockdown ADSCs but expression was rescued by including the miR-30a-3p inhibitor in the osteoblastic process. ALP activity and mineralized bone matrix confirmed the function of circRNA-23525/miR-30a-3p in osteogenesis. Taken together, the current study demonstrated that circRNA-23525 regulates Runx2 expression via targeting miR-30a-3p and is thus a positive regulator in the osteoblastic differentiation of ADSCs.

The circular RNAs differential expression profiles in the metastasis of salivary adenoid cystic carcinoma cells.

In order to reveal circular RNAs (circRNAs) differential expression profiles and investigate the function and mechanism of circRNAs in the metastasis of salivary adenoid cystic carcinoma (SACC), microarray was used to detect differentially expressed circRNAs in SACC-83 and SACC-lung metastasis (LM) cell lines. Up-regulated circRNAs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to further predict their function. Expression of candidate circRNA and microRNA (miRNA) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). Constructed circRNA-miRNA-mRNA co-expression network was based on TargetScan, miRanda databases. Wound healing and transwell assays were completed to examine the effects of hsa_circRNA_001982 and miR-181a-5p on cell migration and invasion. qRT-PCR confirmed hsa_circRNA_092556, hsa_circRNA_101379, and hsa_circRNA_001982 up-regulation in SACC-LM. miR-181a-5p was down-regulated in SACC-LM and correlated with up-regulated hsa_circRNA_001982. Wound healing and transwell assays indicated that silencing hsa_circRNA_001982 inhibited the migration and invasion of the SACC-LM cells. Furthermore, over-expression of hsa_circRNA_001982 promoted the migration and invasion of SACC-83 cells. Interestingly, up-regulation or down-regulation of miR-181a-5p led to the opposite result in wound healing and transwell assays. Overall, differential expression circRNA profiles in SACC-83 and SACC-LM cells may reveal potential targets and a novel mechanism of circRNAs in the metastasis of SACC. Moreover, the interaction of hsa_circRNA_001982/miR-181a-5p is closely related to the metastasis of SACC cells.

Combined Use of Specially-Designed Digital Surgical Guides and Pre-Formed Reconstruction Plate to Treat Bilateral Mandibular Fracture.

This paper describes the application of a modified digital surgical guide, an occlusal template and a pre-formed reconstruction titanium plate in the open reduction and internal fixation of a bilateral mandibular fracture. Bilateral mandibular fracture is a commonly encountered simple type of fracture. However, even for an experience surgeon, achieving precise treatment remains a challenge due to the movable temporomandibular joint, unstable fractured segments, the difficulty in forming a reconstruction plate, and the lack of an effective stabilizing and locating device. In this case, the surgeon used a specially-designed modified guide together with a reconstruction plate and an occlusal template to treat a bilateral mandible fracture, effectively improving the accuracy and the medical outcome of the operation, saving operation time and reducing postoperative complications.

Differential Expression Profiles of Circular RNAs During Osteogenic Differentiation of Mouse Adipose-Derived Stromal Cells.

Osteogenesis is a complex and tightly regulated process. Circular RNAs (circRNAs) are covalently closed RNA molecules which are thought to play a significant role in bone metabolism. The purpose of this study was to investigate the expression and putative function of circRNAs during the osteogenic differentiation of mouse adipose-derived stromal cells (mADSCs). circRNA microarrays were used to determine differential circRNAs expression at different stages during osteogenesis of mADSCs. The most frequent differentially expressed circRNAs were selected by Venn analysis and clustered among the three induced groups. In addition, bioinformatic analyses (gene ontology, pathway, and co-expression network analysis) were used to further investigate these differentially expressed circRNAs. A total of 14,236 circRNAs were detected, of which 43 circRNAs (40 upregulated) were consistently altered at indicated time points during osteogenic differentiation of mADSCs. The exonic circRNAs represented a significantly larger proportion among the differentially expressed circRNAs compared to other types of circRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes biological pathway analysis were performed to evaluate the functions of differentially expressed circRNAs during the osteogenic process. Our circRNA-miRNA co-expression network showed that miR-338-3p was correlated with upregulation of two circRNAs (mmu_circRNA_013422, mmu_circRNA_22566). Our data on circRNA expression profiles may provide valuable insight into circRNA function during osteogenic differentiation of mADSCs. Additionally, the circRNA-miRNA-mRNA pathways may provide information on novel mechanisms and targets for clinical investigations on bone formation and regeneration.

Psychometric properties of the Sport Courage Scale for Chinese athletes.

Objective: To revise Sport Courage Scale (SCS) suitable for Chinese athletes. Methods: Six hundred and eighty three athletes were selected for verification factor analysis, correlation analysis, reliability analysis, and independent sample t-test using the method of random sampling of the entire group. Results: Confirmatory factor analysis model showed that model 1 (25 items) failed to fit the data; while model 2 (20 items) was finally accepted with its five-factor model. The factor structure consists of 5 dimensions (χ2/df = 2.262;CFI = 0.969;TLI = 0.963; RMSEA = 0.043; SRMR = 0.044). Cronbach's α of the final version of SCS was 0.845, and the corrected correlation coefficient between the items and the total score of the scale was between 0.352 and 0.788. Conclusion: Revised SCS has good reliability and validity and can be used as a measurement tool for the sports courage of athletes in China.

Use of modified 3D digital surgical guides in the treatment of complex mandibular fractures.

The objective of this study was to evaluate the use of 3D modified digital surgical guide plates combined with preformed titanium plates in the treatment of complex mandibular fractures. Patients with complex mandibular fractures were randomized into three groups. Group A was treated with a combination of 3D modified digital surgical guide plates and preformed titanium plates, Group B was treated with preformed titanium plates only, and Group C was treated conventionally. The key design point of the guide plates is the "slot" structure, which is crucial for accurately locating the preformed titanium plate. Clinical outcomes, including facial symmetry, surgical accuracy, and maximum deviation were quantitatively assessed postoperatively. Twenty-two patients were recruited for this study, eight for Group A, six for Group B, and eight for Group C. Group A exhibited better postoperative clinical outcomes. Among three groups, significant improvements were found in Group A for facial symmetry (S1 [0.74 ± 0.17 mm, P < 0.001], S2 [0.86 ± 0.21 mm, P = 0.004], S3 [0.92 ± 0.26 mm, P < 0.001], S4 [0.32 ± 0.09 mm, P < 0.001], S5 [0.47 ± 0.16 mm, P = 0.042], S6 [0.35 ± 0.04 mm, P = 0.001], S10 [0.50 ± 0.31 mm, P = 0.048], S11 [0.97 ± 0.29 mm, P = 0.018]) and surgical accuracy (T1 [R, 0.56 ± 0.18 mm, P = 0.021], T1 [L, 0.60 ± 0.30 mm, P = 0.022], T2 [L, 0.76 ± 0.21 mm, P = 0.006], T4 [R, 0.37 ± 0.15 mm, P < 0.001], T4 [L, 0.40 ± 0.15 mm, P = 0.001], T8 [R, 0.40 ± 0.15 mm, P = 0.007], T8 [L, 0.31 ± 0.29 mm, P = 0.001], T9 [L, 0.51 ± 0.33 mm, P = 0.042], T10 [R, 0.58 ± 0.28 mm, P = 0.049], T10 [L, 0.53 ± 0.34 mm, P = 0.046], T11 [R, 0.54 ± 0.13 mm, P = 0.021], T12 [0.45 ± 0.16 mm, P = 0.003]). The ideal postoperative effect was found in Group A with maximum deviation analysis. 3D printed modified digital surgical guide plates can effectively improve treatment outcomes in complex mandibular fractures.

Application of optimized digital surgical guides in mandibular resection and reconstruction with vascularized fibula flaps: Two case reports.

RATIONALE: Currently, digital surgical techniques have been widely used in the precise treatment of mandibular resection and reconstruction with fibula flaps. Utilizing these innovative techniques in surgical planning and hardware fabrication before surgery has shown to provide great help. However, it is difficult for even experienced surgeons to place the preformed reconstruction plate in the same position as its preoperative design, causing surgical results to differ from preoperative planning. This study aims to solve these acknowledged challenges by creating newly designed equipment. PATIENT CONCERNS: Two patients suffering from long-term expansion of the mandible were admitted to our department. Case I was a 39-year-old female patient who was concerned about the disease in the middle of the mandible, Case II was a 45-year-old female patient who was concerned about the disease at the left mandibular angle and ramus region. DIAGNOSES: Two patients were diagnosed with the mandibular ameloblastoma based on computed tomography (CT) scan and pathological results. INTERVENTIONS: Personalized 3-dimensional (3D) surgical guides were applied to 2 patients with mandibular ameloblastoma who underwent mandibular resection and reconstruction with vascularized fibula flaps using a specially optimized and designed reconstruction guide plate. OUTCOMES: We achieved precise mandibular repair with such a guide in full accordance with the preoperative plan and ensured the restoration of patient facial symmetry. LESSONS: Optimized reconstruction guide template could accurately locate the preformed reconstruction plate. This component had the ability to ensure that the location of the actual reconstruction plates were highly consistent with preoperative designed models.

The role of antimiR-26a-5p/biphasic calcium phosphate in repairing rat femoral defects.

Although miRNAs have been implicated in the osteogenic differentiation of stem cells, their role in bone repair and reconstruction in tissue­engineered bone grafts remains unclear. We previously reported that microRNA (miR)­26a­5p inhibited the osteogenic differentiation of adipose­derived mesenchymal stem cells (ADSCs), and that antimiR­26a­5p exerted the opposite effect. In the present study, the role of miR­26a­5p­ and antimiR­26a­5p­modified ADSCs combined with biphasic calcium phosphate (BCP) scaffolds was evaluated in a rat femur defect model. The aim of the present study was to improve the understanding of the role of miR­26a­5p in bone regeneration in vivo, as well as to provide a new method to optimize the osteogenic ability of BCPs. ADSCs were infected with Lv­miR­26a­5p, Lv­miR­NC, Lv­antimiR­26a­5p or Lv­antimiR­NC respectively, and then combined with BCP scaffolds to repair rat femoral defects. Using X­rays, micro­computed tomography and histology at 2, 4, and 8 weeks postoperatively, the quantity and rate of bone regeneration were analyzed, revealing that they were the highest in animals treated with antimiR­26a­5p and the lowest in the miR­26a­5p treatment group. The expression levels of osteocalcin, collagen I, Runt­related transcription factor 2, Wnt family member 5A and calmodulin­dependent protein kinase II proteins were positively correlated with the bone formation rate. Taken together, the present results demonstrated that miR­26a­5p inhibited bone formation while antimiR­26a­5p accelerated bone formation via the Wnt/Ca2+ signaling pathway. Therefore, antimiR­26a­5p­modified ADSCs combined with BCP scaffolds may be used to construct an effective tissue­engineering bone graft for bone repair and reconstruction.