Mandibular stability and condylar changes following orthognathic surgery in mandibular hypoplasia patients associated with preoperative condylar resorption.

OBJECTIVES: To evaluate postoperative mandibular stability and condylar changes in patients with mandibular hypoplasia and preoperative condylar resorption (CR) undergoing orthognathic surgery. MATERIALS AND METHODS: Fifty-four patients were included in this retrospective study. Computed tomography (CT) scans were acquired preoperatively (T0), 2-7 days immediate postoperatively (T1), and at least 1 year postoperatively (T2). Three-dimensional (3D) cephalometric analysis and measurements of condylar angle, volume, and position (joint spaces) were performed. A 2-mm mandibular relapse was deemed clinically acceptable. We also analyzed the correlations between relapse and postoperative CR and susceptible factors using a multivariate logistic regression model. RESULTS: The results showed one year after the surgery, the average mandibular relapse was 1.0 mm (p < 0.05), and the average reduction of condylar volume was 152.4 mm3 (12.7%). Condyle-fossa relationships were improved immediately after the surgery, with a tendency of returning to their original state in the follow-up (p < 0.05). Anteroposterior advancement at point B (B-CP advancement) at T1 and superior joint space (SJS) at T0 were significantly correlated with mandibular relapse, and postoperative CR was mainly associated with vertical increasement at point B (B-AP increasement) at T1. The optimal cut-off values were as follows: 1.6 mm for SJS, 4.2 mm for B-CP advancement, and 1.8 mm for B-AP increasement. Concomitant advancement Genioplasty showed no significant correlation with relapse and postoperative CR. CONCLUSIONS: While patients with mandibular hypoplasia and preoperative CR were vulnerable to further condylar resorption after mandibular advancement, the treatment outcomes were generally clinically acceptable. Postoperative relapse was associated with a larger than 4.2 mm of mandibular advancement measured at B-CP and a larger than 1.6 mm of superior joint space measured at SJS, and postoperative CR was associated with a larger than 1.8 mm of mandibular vertical increasement measured at B-AP. CLINICAL RELEVANCE: The findings of this study suggested that the mandibular advancement might be limited to 5 mm for patients with preoperative CR. A concomitant advancement genioplasty might also be considered to achieve a better facial profile in these patients.

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.

Computer-Assisted Distraction Osteogenesis in the Treatment of Hemifacial Microsomia.

PURPOSE: To investigate the application of computer-assisted surgical planning and virtual guide in distraction osteogenesis for patients with hemifacial microsomia. METHODS: Eight patients diagnosed with unilateral hemifacial microsomia were enrolled in this study. Preoperative surgical planning and simulation were performed on three-dimensional model. Distraction was simulated on virtual model and the new morphology of the mandible was predicted. Mandibular ramus osteotomy and distractor implant was performed under the guidance of tooth-borne virtual guide. Postoperative evaluation of the intervention was performed by comparison of surgical planning and actual result. RESULTS: Preoperative planning, simulation, osteotomy and distractor implant under the guidance of virtual guide were performed successfully on all patients. Tooth-borne guide defined the osteotomy line and accurate position of distractor. Facial symmetry was greatly improved. The osteogenesis and neomandible contour was checked by postoperative computed tomography, and a good matching with the preoperative planning was achieved. CONCLUSIONS: Computer-assisted surgical planning and intraoperative virtual guide shows its great value in improving the accuracy of distraction osteogenesis and restoring facial symmetry. It is regarded as a valuable technique in this potentially complicated procedure.

Tcof1-Related Molecular Networks in Treacher Collins Syndrome.

Treacher Collins syndrome (TCS) is a rare, autosomal-dominant disorder characterized by craniofacial deformities, and is primarily caused by mutations in the Tcof1 gene. This article was aimed to perform a comprehensive literature review and systematic bioinformatic analysis of Tcof1-related molecular networks in TCS. First, the up- and down-regulated genes in Tcof1 heterozygous haploinsufficient mutant mice embryos and Tcof1 knockdown and Tcof1 over-expressed neuroblastoma N1E-115 cells were obtained from the Gene Expression Omnibus database. The GeneDecks database was used to calculate the 500 genes most closely related to Tcof1. Then, the relationships between 4 gene sets (a predicted set and sets comparing the wildtype with the 3 Gene Expression Omnibus datasets) were analyzed using the DAVID, GeneMANIA and STRING databases. The analysis results showed that the Tcof1-related genes were enriched in various biological processes, including cell proliferation, apoptosis, cell cycle, differentiation, and migration. They were also enriched in several signaling pathways, such as the ribosome, p53, cell cycle, and WNT signaling pathways. Additionally, these genes clearly had direct or indirect interactions with Tcof1 and between each other. Literature review and bioinformatic analysis finds imply that special attention should be given to these pathways, as they may offer target points for TCS therapies.

Effects of aging on ocular vestibular-evoked myogenic potential using ER-3A insert earphone and B81 bone vibrator.

Purpose: Aging is a process associated with degeneration and dysfunction of peripheral vestibular system or apparatus. This study aimed to investigate the influence of aging on ocular vestibular-evoked myogenic potential (oVEMP) response rates and recording parameters using the B81 bone vibrator and compare them with air conduction stimuli (ACS) oVEMP response characteristics. Methods: In 60 healthy participants aged 10-71 years (mean age 39.9; 29 male participants), the oVEMP response was elicited using a B81 bone vibrator and an ER-3A insert earphone. The effects of age and stimulus on oVEMP response rates and recording parameters were evaluated. Results: Response rates and amplitudes declined with aging using either ACS or bone-conducted vibration (BCV) stimulation, particularly in individuals over 60 years of age, whereas thresholds increased and N1 latencies were prolonged. BCV showed fewer risks of absent oVEMP response than ACS (p = 0.002). BCV acquired higher amplitudes (p < 0.001), lower thresholds, and shorter N1 and P1 latencies (all p < 0.001) than ACS. Conclusions: The absence of an oVEMP response may be attributed to aging rather than a concurrent vestibular disorder. B81-BCV likely produces higher mechanical drives to the vestibular hair cells at safer and non-traumatic levels compared with ACS and therefore may be more likely to evoke a response in the elderly cohort, whose vestibular function and mechanical sensitivity have declined. Thus, B81-BCV stimulation is more effective and safer to elicit oVEMPs, and it should be recommended when ACS fails in the clinic, particularly in the elderly population.

Reducing relapse and accelerating osteogenesis in rapid maxillary expansion using an injectable mesoporous bioactive glass/fibrin glue composite hydrogel.

Rapid maxillary expansion (RME), as a common treatment for craniomaxillofacial deformity, faces the challenge of high relapse rates and unsatisfactory therapeutic effects. In this study, a standardized Sprague-Dawley (SD) rat RME model was first established with a modified expander as well as retainer design and optimized anterior maxillary expanding force of 100 g which exerted the most synchronized mobility of mid-palatal suture and incisors. Via the standardized model, the high relapse rate was proven to be attributed to insufficient osteogenesis in expanded suture, requiring long-term retainer wearing in clinical situations. To reduce the relapse rate, mesoporous bioactive glass/fibrin glue (MBG/FG) composite hydrogels were developed for an in situ minimal invasive injection that enhance osteogenesis in the expanded palate. The component of 1 wt% MBG was adopted for enhanced mechanical strength, matched degradation rate and ion dissolution, excellent in vitro biocompatibility and osteoinductivity. Effects of 1%MBG/FG composite hydrogel on osteogenesis in expanded mid-palatal sutures with/without retention were evaluated in the standardized model. The results demonstrated that injection of 1%MBG/FG composite hydrogel significantly promoted bone formation within the expanded mid-palatal suture, inhibited osteoclastogenesis and benefited the balance of bone remodeling towards osteogenesis. Combination of retainer and injectable biomaterial was demonstrated as a promising treatment to reduce relapse rate and enhance osteogenesis after RME. The model establishment and the composite hydrogel development in this article might provide new insight to other craniomaxillofacial deformity treatment and design of bone-repairing biomaterials with higher regenerative efficiency.

The Transcription Factor Foxc1 Promotes Osteogenesis by Directly Regulating Runx2 in Response of Intermittent Parathyroid Hormone (1-34) Treatment.

Parathyroid hormone (PTH) is crucial for bone remodeling. Intermittent PTH (1-34) administration stimulates osteogenesis and promotes bone formation; however, the possible targets and underlying mechanisms still remain unclear. In this study, functional links between PTH and Foxc1, a transcription factor reported to be predominant in skeletal development and formation, were indicated. We determined the impacts of Foxc1 on in vitro osteogenic differentiation and in vivo bone regeneration under intermittent PTH induction, and further explored its possible targets. We found that the expression level of Foxc1 was upregulated during osteogenic induction by intermittent PTH treatment, and the elevated expression of Foxc1 induced by PTH was inhibited by PTH1R silencing, while rescued by intermittent PTH supplement. By gain- and loss-of-function strategies targeting Foxc1 in MC3T3-E1 cells, we demonstrated that Foxc1 could promote in vitro osteogenic differentiation by intermittent PTH induction. Moreover, immunofluorescence analysis indicated the nuclear co-localization of Foxc1 with Runx2. Luciferase-reporter and chromatin immunoprecipitation analysis further confirmed that Foxc1 could bind to the P1 promoter region of Runx2 directly, which plays an indispensable part in osteogenic differentiation and bone mineralization. Meanwhile, we also revealed that Foxc1 could promote bone regeneration induced by intermittent PTH treatment in vivo. Taken together, this study revealed the role and mechanism of Foxc1 on in vitro osteogenic differentiation and in vivo bone regeneration in response of intermittent PTH treatment.

A microfluidic chip with double-sided herringbone microstructures for enhanced capture of rare tumor cells.

A microfluidic chip with single-sided herringbone microstructure has been developed to isolate circulating tumor cells (CTCs) from blood samples of cancer patients. Here, we describe a new double-sided herringbone chip in which staggered herringbone micromixers are placed on both top and bottom surfaces of microchannels. The double-sided herringbone structure enables a high CTC capture efficiency of whole blood samples without depletion of red blood cells because of the effects of leukocyte margination and plasma skimming. However, compared with the traditional single-sided herringbone chip, the double-sided herringbone chip has more complicated geometrical design, leading to a difficulty in experimental optimization of geometrical parameters. In this study, we developed an analytical model to geometrically optimize the herringbone chip by investigating the interactions between cells and antibody-immobilized device surfaces for enhancing CTC capture efficiency. On-chip cell capture experiments for validating modeling results were performed by spiking cultured EpCAM-positive tumor cells into blood samples from healthy donors. Based on the geometrical parameters optimized from the single-sided herringbone chip, the geometrically optimized double-sided herringbone chip enables a capture efficiency of 94 ± 4% of rare tumor cells directly from whole blood.

[The effect of Foxc2 overexpression on the osteogenic properties of C3H10T1/2 cells].

PURPOSE: To investigate the effect of Foxc2 overexpression on osteogenic and adipogenic differentiation of C3H10T1/2 cells. METHODS: C3H10T1/2 cells were transfected with plenti-Foxc2 and selected with puromycin for stable clones. The expression of Foxc2 was determined by real-time PCR and Western blot. Cell proliferation was detected by CCK-8 kit. Cell cycle and apoptosis were detected by flow cytometry. The level of osteogenic biomarkers Runx2, OPN, OCN and adipogenic biomarker PPARγ were quantified by real-time PCR and Western blot. Alkaline phosphatase (ALP) staining and oil red staining were conducted to evaluate the effect of Foxc2 overexpression on osteogenic and adipogenic differentiation. Statistical analysis was performed using SPSS 17.0 software package. RESULTS: C3H10T1/2-Foxc2 cell line was successfully constructed and verified by direct sequencing and Foxc2 overexpression in vitro. Cell proliferation was reduced and cell cycle was blocked in G1/G0 phase. Enhanced ALP staining and reduced oil red staining were observed in C3H10T1/2-Foxc2 cells as compared with the control. Foxc2 overexpression up-regulated Runx2, OPN, OCN during osteogenic differentiation and down-regulated PPARγduring adipogenic differentiation. CONCLUSIONS: C3H10T1/2 cell line stably expressing Foxc2 gene was successfully established, cell proliferation was reduced, osteogenesis biomarkers were up-regulated during the osteogenesis by overexpression Foxc2, PPARγwas down-regulated during adipogenesis.

Anterior maxillary segmental distraction in the treatment of severe maxillary hypoplasia secondary to cleft lip and palate.

Anterior maxillary segmental distraction (AMSD) is an effective surgical procedure in the treatment of maxillary hypoplasia secondary to cleft lip and palate. Its unique advantage of preserving velopharyngeal function makes this procedure widely applied. In this study, the application of AMSD was described and its long-term stability was explored. Eight patients with severe maxillary hypoplasia secondary to CLP were included in this study. They were treated with AMSD using rigid external distraction (RED) device. Cephalometric analysis was performed twice at three time points for evaluation: before surgery (T1), after distraction (T2), and 2 years after treatment (T3). One-way analysis of variance was used to assess the differences statistically. All the distractions completed smoothly, and maxilla was distracted efficiently. The value of SNA, NA-FH, Ptm-A, U1-PP, overjet and PP (ANS-PNS) increased significantly after the AMSD procedure (P < 0.05), with the mean overjet increased by 14.28 mm. However, comparison of cephalometric analysis between T2 and T3 showed no significant difference (P > 0.05). Changes of palatopharyngeal depth and soft palatal length were insignificant. AMSD with RED device provided an effective way to correct maxillary hypoplasia secondary to CLP, extended the palatal and arch length, avoided damage on velopharyngeal closure function and reduced the relapse rate. It is a promising and valuable technique in this potentially complicated procedure.

An integrated microfluidic chip system for single-cell secretion profiling of rare circulating tumor cells.

Genetic and transcriptional profiling, as well as surface marker identification of single circulating tumor cells (CTCs) have been demonstrated. However, quantitatively profiling of functional proteins at single CTC resolution has not yet been achieved, owing to the limited purity of the isolated CTC populations and a lack of single-cell proteomic approaches to handle and analyze rare CTCs. Here, we develop an integrated microfluidic system specifically designed for streamlining isolation, purification and single-cell secretomic profiling of CTCs from whole blood. Key to this platform is the use of photocleavable ssDNA-encoded antibody conjugates to enable a highly purified CTC population with <75 'contaminated' blood cells. An enhanced poly-L-lysine barcode pattern is created on the single-cell barcode chip for efficient capture rare CTC cells in microchambers for subsequent secreted protein profiling. This system was extensively evaluated and optimized with EpCAM-positive HCT116 cells seeded into whole blood. Patient blood samples were employed to assess the utility of the system for isolation, purification and single-cell secretion profiling of CTCs. The CTCs present in patient blood samples exhibit highly heterogeneous secretion profile of IL-8 and VEGF. The numbers of secreting CTCs are found not in accordance with CTC enumeration based on immunostaining in the parallel experiments.