Osteoclast-Driven Osteogenesis, Bone Remodeling and Biomaterial Resorption: A New Profile of BMP2-CPC-Induced Alveolar Bone Regeneration.

This bedside-to-bench study aimed to systematically investigate the value of applying BMP2-loaded calcium phosphate cement (BMP2-CPC) in the restoration of large-scale alveolar bone defects. Compared to deproteinized bovine bone (DBB), BMP2-CPC was shown to be capable of inducing a favorable pattern of bone regeneration and bone remodeling accompanied by active osteoclastogenesis and optimized biomaterial resorption when applied in reconstructive periodontally accelerated osteogenic orthodontics (PAOO) surgery. To verify the regulatory role of osteoclasts in the BMP2-CPC-induced pattern of bone regeneration, in vitro and in vivo studies were designed to elucidate the underlying mechanism. Our results revealed that osteoclasts played a multifaceted role (facilitating osteogenesis, bone remodeling and biomaterial resorption) in the BMP2-CPC-induced bone regeneration. Osteoclasts contributed to the osteogenic differentiation of mesenchymal stem cells (MSCs) by secreting calcium ions, CTHRC1 and PDGF-B. Moreover, the increased osteoclasts promoted the remodeling of new bone and BMP2-CPC resorption, leading to a harmonized replacement of biomaterials with mature bone. In conclusion, the in vitro and in vivo experimental results corresponded with the clinical results and showed the optimized properties of BMP2-CPC in activating osteoclast-driven bone regeneration and remodeling, thus indicating the highly promising prospects of BMP2-CPC as an ideal therapeutic for alveolar bone defects.

Amniotic fluid-derived stem cells mixed with platelet rich plasma for restoration of rat alveolar bone defect.

Stem cells isolated from the amniotic fluid have been shown as a promising candidate for cell therapy and tissue engineering. However, the experimental and preclinical applications of amniotic fluid-derived stem cells (AFSCs) in the very field of maxillofacial bone tissue engineering are still limited. In this study, rat AFSCs were successfully harvested and characterized in vitro. The rat AFSCs showed typical fibroblastoid morphology, stable proliferation activity and multi-differentiation potential. Flow-cytometry analysis demonstrated that these cells were positive for CD29, CD44, and CD90, while negative for hematopoietic markers such as CD34 and CD45. The regenerative performance of AFSCs-premixed with platelet rich plasma (PRP) gel in restoration of alveolar bone defect was further investigated using a modified rat maxillary alveolar defect model. Micro-computer tomography and histological examination showed a superior regenerative capacity of AFSCs-premixed with PRP gel at both 4 and 8 weeks after operation comparing with control groups. Moreover, the implanted AFSCs can survive in the defect site and directly participate in the bone tissue regeneration. Taken together, these results indicated the feasibility of an AFSCs-based alveolar bone tissue engineering strategy for alveolar defect restoration.

A correlational study of serum alkaline phosphatase level and developmental mandibular laterognathism.

The abnormal cartilage/bone metabolism in unilateral condyle may be a direct factor that contributes to developmental mandibular laterognathism. However, although many molecules have been demonstrated to play crucial roles in the development of temporomandibular joints, the exact molecular mechanisms that lead to the disrupted condylar cartilage/bone development were greatly unknown. In this retrospective study, our findings revealed that serum alkaline phosphatase (ALP) level in adult patients with developmental mandibular laterognathism was lower than that in control subjects, and the serum ALP levels continue to reduce in adult patients (>20 years old). Although the exact relationship between the lower serum ALP level and developmental mandibular laterognathism is unclear, the findings further support the opinion that the condylar growth may sustain for a long time in the affected condyle in patients with developmental mandibular laterognathism and offer an alternative choice to use total serum ALP activity as a possible biomarker to assess condylar growth activity in patients with developmental mandibular laterognathism.

Characterization of a micro-roughened TiO2/ZrO2 coating: mechanical properties and HBMSC responses in vitro.

Previous studies have shown that using ZrO2 as a second phase to bioceramics can significantly increase the bonding strength of plasma-sprayed composite material. In the present study, micro-roughened titanium dioxide/zirconia (TiO2/ZrO2) (30 wt% ZrO2) coating and TiO2 coating were plasma-sprayed onto Ti plates. The micro-structural characteristics and mechanical properties of both coatings were investigated. Furthermore, the biological behavior and osteogenic differentiation of human bone marrow mesenchymal stem cells (HBMSCs) on both TiO2/ZrO2 and TiO2 coatings were compared. The results indicated that the shear bond strength and microhardness of TiO2/ZrO2 coating were statistically higher than those of TiO2 coating. Scanning electron microscope observation revealed that more irregularly shaped protuberances and denser pores were formed on the surface of TiO2/ZrO2 coating compared with those of TiO2 coating. Further comparative analysis of HBMSC proliferation and osteogenic differentiation on both coatings showed that significantly higher cellular alkaline phosphatase activity and expression levels of Runx2 and Osterix at day 10 after osteogenic culture were found on TiO2/ZrO2 coating compared with TiO2 coating, while no statistically significant difference in cell proliferation and extracellular calcium deposition was observed. The present study suggests that TiO2/ZrO2 coating may be favorable for dental implant applications.

Accurate movement of jaw segment in virtual 3D orthognathic surgery.

In traditional virtual 3D orthognathic surgery, after repositioning the maxillary segment to the desired position, surgeons usually roughly rotate or adjust the mandibular segment to obtain a relatively good relationship with maxillary dentition to calculate the virtual terminal occlusion splint. However, surgeons are not easy to avoid penetrability, overlap, or an overly large space existing between the maxillary and mandibular dentitions during this process. The present report offered a new method to obtain a suitable virtual terminal occlusal splint that could avoid penetrability, overlap, or an overly large space between the maxillary and mandibular dentitions, and simultaneously accurately moving the maxillary or mandibular segment to the desired position utilizing the planned terminal occlusion plaster models in virtual orthognathic surgery. For double jaw surgery, after aligning the planned plaster models to the 3D maxilla and mandible, we could simultaneously move the maxillary and mandibular segment as a whole that maintain the planned terminal occlusion to the desired position. This present method may enhance the accuracy of 3D virtual orthognathic surgery and save plenty of time spend on virtual surgery simulation, which also offers a useful educational method for training junior surgeons and students.

Evaluation of optimal single-photon emission computed tomography reference value and three-dimensional mandibular growth pattern in 54 Chinese unilateral condylar hyperplasia patients.

BACKGROUND: The research aimed to evaluate the optimal Single-Photon Emission Computed Tomography (SPECT) cut-off value in differentiating condylar growth activeness, to observe 3-dimensional (3D) mandibular growth pattern, and to explore the potential correlation between 3D measurement parameters and SPECT uptake ratios in Chinese unilateral condylar hyperplasia (UCH) patients. METHODS:  Data of fifty-four Chinese UCH patients were analyzed retrospectively. All patients underwent SPECT within 1 month before or after the first CT examination (CT1); and received a second CT examination at least 12 months later (CT2). Data from CT scans were analyzed by comparing bilateral differences between CT1 and CT2. The sensitivity and specificity of SPECT were calculated by the receiver operating characteristic (ROC) curve. Pearson's correlation analysis was performed to investigate whether the mandibular growth was correlated with SPECT value. RESULTS: SPECT had a sensitivity of 68.00% and a specificity of 72.41%, with an area under the ROC curve being 0.709. The optimal SPECT cut-off value for evaluating condylar activity has been determined to be 13%. In patients with an active growing condyle, there was a significant increase in Co-Gn and Co-Go, but not in Go-Gn, Go-MF, or MF-Gn. Pearson's correlation analysis revealed no correlation between 3D measurement parameters and differences in relative condylar uptake ratios. CONCLUSION: SPECT showed good diagnostic performance in UCH with the cut-off value of 13%. For those with an active growing condyle, the mandible grows diagonally and vertically, while the relative condylar uptake ratio was not directly related to mandibular growth.

Intraoral Condylectomy with 3D-Printed Cutting Guide versus with Surgical Navigation: An Accuracy and Effectiveness Comparison.

This study compares the accuracy and effectiveness of our novel 3D-printed titanium cutting guides with intraoperative surgical navigation for performing intraoral condylectomy in patients with mandibular condylar osteochondroma (OC). A total of 21 patients with mandibular condylar OC underwent intraoral condylectomy with either 3D-printed cutting guides (cutting guide group) or with surgical navigation (navigation group). The condylectomy accuracy in the cutting guide group and navigation group was determined by analyzing the three-dimensional (3D) discrepancies between the postoperative computed tomography (CT) images and the preoperative virtual surgical plan (VSP). Moreover, the improvement of the mandibular symmetry in both groups was determined by evaluating the chin deviation, chin rotation and mandibular asymmetry index (AI). The superimposition of the condylar osteotomy area showed that the postoperative results were very close to the VSP in both groups. The mean 3D deviation and maximum 3D deviation between the planned condylectomy and the actual result were 1.20 ± 0.60 mm and 2.36 ± 0.51 mm in the cutting guide group, and 1.33 ± 0.76 mm and 4.27 ± 1.99 mm in the navigation group. Moreover, the facial symmetry was greatly improved in both groups, indicated by significantly decreased chin deviation, chin rotation and AI. In conclusion, our results show that both 3D-printed cutting-guide-assisted and surgical-navigation-assisted methods of intraoral condylectomy have high accuracy and efficiency, while using a cutting guide can generate a relatively higher surgical accuracy. Moreover, our cutting guides exhibit user-friendly features and simplicity, which represents a promising prospect in everyday clinical practice.

[In vitro biological evaluation of PEGylated poly(glycerol sebacate)/ß-TCP-coating modified magnesium alloy].

PURPOSE: To prepare PEGS/ß-TCP modified magnesium alloy (PEGS/ß-TCP/MZG) membranes by forming a glycolated poly(sebacate)/ß-tricalcium phosphate (PEGS/ß-TCP) coating on the surface of magnesium-zinc-gadolinium alloy (MZG) membranes, and to evaluate the osteogenic induction activity and immunomodulatory properties of PEGS/ß-TCP/MZG using the material extract medium. METHODS: PEGS/ß-TCP coating was prepared on the surface of MZG by solvent method, and the PEGS/ß-TCP/MZG membrane was fabricated and compared with PEGS/ß-TCP and MZG to examine the morphology, composition, and hydrophilicity. The amount of magnesium ions released and the pH value of the materials were tested after 3 days of immersion. The cell viability and osteogenic differentiation of MC3T3 cells induced by extract medium were investigated by CCK-8 assay, ALP and mineralized nodule staining. The cell viability and polarization of RAW cells induced by extract medium were then investigated. The expression of macrophage-secreted cytokines was examined by PCR analysis. GraphPad Prism 9.0 software package was used for statistical analysis. RESULTS: PEGS/ß-TCP/MZG membranes with PEGS/ß-TCP coating tightly embedded with MZG were successfully fabricated, and the material had good hydrophilicity. The results of degradation experiments indicated that the PEGS/ß-TCP coating effectively slowed down the degradation rate of MZG, leading to a lower pH value and concentration of Mg2+ ion in the extract medium of PEGS/ß-TCP/MZG group. The results of in vitro cell experiments showed that PEGS/ß-TCP/MZG had no significant effect on the proliferation activity of both MC3T3-E1 and macrophages. PEGS/ß-TCP/MZG significantly enhanced the expression of ALP and mineralized nodule staining in MC3T3-E1. Although there was no significant difference in macrophage polarization pattern between PEGS/ß-TCP and PEGS/ß-TCP/MZG groups, PEGS/ß-TCP/MZG further reduced inflammation based on the immunomodulation of PEGS/ß-TCP coating related TNF-α expression and increased osteogenesis related TGF-ß expression. CONCLUSIONS: MZG membrane modified by PEGS/ß-TCP may provide a new material option for the development of bone tissue engineering.

Effects of inferior alveolar nerve rupture on bone remodeling of the mandible: A preliminary study.

Although various animal studies have indicated that sensory nerves played an important role in bone metabolism and nerve injury could impair the process of bone remodeling, the actual effect of sensory nerve rupture on human bones remains unclear. The aim of this preliminary study was to investigate the effect of inferior alveolar nerve (IAN) rupture on mandibular bone remodeling of patients underwent bilateral sagittal split ramus osteotomy (BSSRO).Ten patients with unilateral IAN rupture during BSSRO were involved in this study. Neurosensory examinations were employed to assess the sensory function of bilateral IAN. The remodeling process of the post-operational mandible was evaluated by panoramic radiographs and computed tomography (CT) scans.Neurosensory examinations indicated that nerve rupture resulted in significant hypoesthesia at the IAN-rupture side. Assessment of panoramic radiographs showed no evident alterations of bone structure at the IAN-rupture side of mandible. Evaluation of CT images also indicated no statistical difference in bone density and thickness between IAN-rupture side and contralateral side.Accordingly, our study indicated that IAN rupture may not significantly impair the short-term bone remodeling process of human mandible.

Changes of disc status in adult patients with condylar head fracture who did or did not undergo disc anchoring operation.

PURPOSE: Views on treatment procedures for condylar head fractures (CHFs) are far from reaching a consensus. The aim of this study was to evaluate the changes in disc status for anteromedial disc displacement with anchorage (AMDDwA) and without anchorage (AMDDwoA - just suturing to the adjacent TMJ soft tissue) in adult CHFs, to get a better understanding of this very complex process and to show that rigid disc anchorage is an essential technique for the treatment of CHF during the open reduction and internal fixation (ORIF). PATIENTS AND METHODS: 144 temporomandibular joints (TMJ) in 95 patients were included in this retrospective study, and were divided into an AMDDwA group (50 TMJs in 38 patients) and an AMDDwoA group (94 TMJs in 57 patients) based on the different surgical procedures. The joints were quantitatively and qualitatively assessed for disc length and disc morphology preoperatively and at follow-up visits. Other variables, such as disc position, joint effusion, retrodiscal tear and lateral capsular tear, were also evaluated. Paired t-tests, Wilcoxon signed rank tests, independent t-tests and χ2 tests were used to assess intragroup and intergroup differences. RESULTS: The results showed that discs became shorter, moved further forward and distorted more seriously in the AMDDwoA group. In contrast, discs became longer, maintained a normal disc-condyle relationship in the AMDDwA group. Joint effusion, retrodiscal tear, and lateral capsular tear healed well in both groups. CONCLUSION: Taking these findings together suggests that the rigid disc anchorage is an alternative technique for the treatment of CHF.

Dental and periodontal phenotypes of Dlx2 overexpression in mice.

Distal-less homeobox 2 (Dlx2) is a member of the homeodomain family of transcription factors and is important for the development of cranial neural crest cells (CNCCs)­derived craniofacial tissues. Previous studies revealed that Dlx2 was expressed in the cementum and a targeted null mutation disrupted tooth development in mice. However, whether Dlx2 overexpression may impair in vivo tooth morphogenesis remains to be elucidated. The present study used a transgenic mouse model to specifically overexpress Dlx2 in neural crest cells in order to identify the dental phenotypes in mice by observation, micro­computed tomography and histological examination. The Dlx2­overexpressed mice exhibited tooth abnormalities including incisor cross­bite, shortened tooth roots, increased cementum deposition, periodontal ligament disorganization and osteoporotic alveolar bone. Therefore, Dlx2 overexpression may alter the alveolar bone, cementum and periodontal ligament (PDL) phenotypes in mice.

Overexpression of Dlx2 leads to postnatal condyle degradation.

Distal-less homeobox 2 (Dlx2), a member of the Dlx family of transcription factors, is important for the development of craniofacial tissues. Previous studies based on knock­out mutant mice revealed that Dlx2 primarily disturbed the development of tissues from maxillary arch. The present study used a transgenic mouse model to specifically overexpress Dlx2 in neural crest cells in order to investigate the role of Dlx2 overexpression in post­natal condyle in mice. The model was constructed and the phenotype observed using gross observation, micro­CT scan and histological examination. The model determined that overexpression of Dlx2 may lead to postnatal condyle malformation, subchondral bone degradation and irregular histological structure of the condylar cartilage. In addition, the expression of osteocalcin in the condyle region was markedly downregulated, whereas expression of msh homeobox 2 was upregulated. The results of the present study suggest that Dlx2 overexpression in cranial neural crest cells would disrupt the development of post­natal condyle, which demonstrates that the expression level and the spatiotemporal expression patterns of Dlx2 may be important in regulating the development of post-natal condyle in mice, and also offered a possible temporal­mandibular joint osteoarthritis model animal for future studies.