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In this article, authors mainly introduce new digital technology in facial bone contouring surgery. In our experience, these new technologies are crucial in ensuring the satisfaction of surgical accuracy. Our previous studies have shown surgeons can use precise pre-operative design to reduce operative time, reduce bleeding during surgery. Additionally, augmented reality can enhance the perspective perception of surgeons combining virtuality and reality. What's more, robot-assisted surgical technology also has a strong application prospect in facial contouring surgery. In the future, the combination of soft tissue contouring surgery will make the facial bone contouring surgery safer and more effective.

A limited number of clinical studies have focused on the changing trends of facial soft tissue after mandibular angle ostectomy. We conducted this study to investigate the changes in facial muscles and facial soft tissue appearance before and after mandibular angle ostectomy.A single-center retrospective cohort study was conducted on female patients admitted to our hospital for mandibular angle ostectomy between 2019 and 2020. The primary predictor variable was time (preoperative vs 6 months postoperative). The primary outcome variables were surface area and total volume of the manually delineated region of interest (ROI) for the masseter and temporalis muscles. We utilized computed tomography data to reconstruct 3-dimensional models to delineate muscle ROI and then measure them computationally. Secondary outcome variables were indicators of mandible appearance in soft tissue including bilateral mandibular angle distance, mandibular ramus height, and mandibular angle value. Age, preoperative body mass index, and ostectomy volume were chosen as covariates for correlation analysis with outcome variables. Paired t tests and Pearson correlation analysis were conducted, and P values.05 were considered statistically significant.A total of 29 female patients (mean age, 26 years; range, 18 to 37 years) who underwent mandibular angle ostectomy in our hospital were included. The surface area and total volume of the masseter muscle ROI were reduced by 2,541.2 ± 1,925.0 mmWe observed statistically significant levels of atrophy of the masseter muscle ROI and expansion of the temporalis muscle ROI 6 months after mandibular angle ostectomy, which may account for appearance changes after surgery. Besides, ostectomy volume positively correlates with postoperative masseter ROI changes. In summary, our study provided empirical evidence illustrating soft tissue alterations in patients who have undergone mandibular angle ostectomy.

In order to reduce the possibility of accidental injury to neurovascular and important tissues, this research conduct preoperative design and intraoperative guidance for fibrous dysplasia through augmented reality technology.Five patients with fibrous dysplasia were selected for three-dimensional (3D) Computed Tomography (CT) scan and 3D model was reconstructed. Considering the navigation plan was comprehensively, the guide plate (composed of card groove, connector, and fixator) was designed and 3D printed. Threedimensional software was used to unify the coordinates of the surgical plan and the guide plate, and the relative position was fixed. Then, the virtual and real overlapping registration is completed on the physical model. Pattern recognition technology is used to identify pre-defined markers in the video images before operation. Finally, the registration results are superimposed into the surgical field of vision to guide and remind surgeons.In this study, the navigation based on augmented reality technology was used in the surgical treatment of 5 cases patients with fibrous dysplasia. The 3D navigation information was displayed in real time in the operative field. The operation was accurate and the postoperative effect was good.This paper introduces an effective visual navigation surgical method in treatment with fibrous dysplasia. The augmented- reality based navigation system achieves individualized precise treatment by displaying 3D navigation directly in the surgical field. It is an effective auxiliary method for future research on craniofacial surgery.

Macrostomia is arare congenital craniofacial deformity that influences the appearance and function of patients. In most cases, it coexists with craniomaxillofacial deformities such as craniofacial microsomia (CFM). This study aimed to analyze the relationship between macrostomia and mandibular hypoplasia so as to facilitate the early detection and diagnosis of children with CFM. It included 236 patients diagnosed with CFM. All underwent facial expression analysis, multi-angle photography, computed tomography, and three-dimensional reconstruction of soft and hard tissues. The clinical classification was performed according to OMENS+. Spearman (rank) correlation analysis was used to analyze the relationship between the severity of macrostomia (C1 and C2) and the degree of mandibular involvement (M1, M2a, M2b, and M3), and the correlation among the components of OMENS+. Of the 80 cases of macrostomia (34%) reported, 72 cases (90%) were C1 and 8 (10%) were C2. The analysis of OMENS+ revealed significant correlations among OMENS+ components. Also, a high correlation was observed between macrostomia (C) and hypoplasia of the mandible (M) ( P = 0.002). Macrostomia was closely related to mandibular hypoplasia among children diagnosed with CFM. These results suggested that patients with macrostomia, who might also have craniofacial malformations caused by other first branchial arch anomalies, should be comprehensively physically examined for other syndromes.

In this study, an AI osteotomy software was developed to design the presurgical plan of mandibular angle osteotomy, which is followed by the comparison between the software-designed presurgical plan and the traditional manual presurgical plan, thus assessing the practicability of applying the AI osteotomy software in clinical practices.(1) Develop an AI osteotomy software: design an algorithm based on convolutional neural networks capable of learning feature point and processing clustering segmentation; then, select 2296 cases of successful 3D mandibular angle osteotomy presurgical plans, followed by using those 2296 cases to train the deep learning algorithm; (2) compare the osteotomy presurgical plan of AI osteotomy software and that of manual: first step: randomly selecting 80 cases of typical female head 3D CTs, and designing those 80 cases by means of AI osteotomy software designing (group A) and manually designing (group B), respectively; second step: comparing several indexes of group A and those of group B, including the efficiency index (time from input original CT data to osteotomy presurgical plan output), the safety index (the minimum distance from the osteotomy plane to the mandibular canal), the symmetry indexes (bilateral difference of mandibular angle, mandibular ramus height and mandibular valgus angle) and aesthetic indexes (width ratio between middle and lower faces (M/L), mandibular angle and mandibular valgus angle).The efficiency index: the design time of group A is 1.768 ± 0.768 min and that of group B is 26.108 ± 1.137 min, with P = 0.000; the safety index: The minimum distances from the osteotomy plane to the mandibular canal are 3.908 ± 0.361mm and 3.651 ± 0.437mm, p = 0.117 in groups A and B, respectively; The symmetry indexes: Bilateral differences of mandibular angle are 1.824 ± 1.834° and 1.567 ± 1.059° in groups A and B, respectively, with P = 0.278; bilateral differences of mandibular ramus height are 2.083 ± 1.263 and 2.965 ± 1.433, respectively, with P = 0.119 in groups A and B; Aesthetic indexes: M/L in groups A and B is 1.364 ± 0.074 and 1.371 ± 0.067, respectively, with P = 0.793; mandibular angles in groups A and B are 127.724 ± 5.800° and 127.242 ± 5.545°, respectively, with P = 0.681; Valgus angles in groups A and B are 11.474 ± 5.380 and 9.743 ± 4.620, respectively, with P = 0.273.With high efficiency, as well as safety, symmetry and aesthetics equivalent to those of a manual design, the AI osteotomy software designing can be used as an alternative method for manual osteotomy designing.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Botulinum toxin injection is a highly efficacious treatment for masseter muscle hypertrophy, while manual injection point localization based on experience can be non-quantitative, subjective and therefore suboptimal and even side-effect risky. To address this important while challenging task, in this paper we present a methodology of automatic ideal point localization for botulinum toxin injection based on automatic segmentation, measurement and quantitative analysis. Specifically, we first present a novel three-dimensional (3D) fully convolutional neural network for fully automatic mandible and masseter regions of interest (RoI) localization and segmentation from head computed tomography (CT) images. Given the segmentation results, the ideal injection points on the face are located using ray casting based automatic thickness measurement. We conducted experiments on an internal dataset consisting of head CT images acquired from 53 patients to evaluate the segmentation performance and localization reliability. The results demonstrate that the segmentation framework outperforms the state-of-the-art method by a significant margin, and the localization system provides intuitive, interactive user interface and reliable injection point decisions.

Mandibular distraction osteogenesis at an early age is the standard hemifacial microsomia treatment. Nevertheless, the recurrence rate remains high and the definition of early age is controversial. We explored the optimal timing for mandibular distraction, when the surrounding skeleton, such as maxilla, can grow compensatory, to reduce recurrence. Hemifacial microsomia patients were prospectively divided into Groups A (1–3 years old) and B (4–6 years old), according to maxillary and mandibular growth curves. Computed tomography scans were obtained before distractor implantation and after removal surgery. Maxillary volume increase percentage was the main outcome indicator; other indicators (maxillary symmetry and complications) were secondary outcomes. Fifty-eight patients were enrolled and all but one patient in Group A (failed distraction) completed the study. Two patients had facial nerve injury and another two had mouth-opening limitation, which was relieved after coracoid resection. The difference in percentage increase in maxillary volume between the affected and unaffected sides was 5.06 ± 2.73% and 3.18 ± 1.99% in Groups A and B, respectively, suggesting better compensatory growth in younger patients (P = 0.004). Maxillary symmetry was apparently elevated after mandibular distraction. Mandibular distraction osteogenesis was confirmed to be feasible and safe at age

Masseter deficits are common in craniofacial microsomia (CFM), however studies on masseter muscle involvement are limited. The aim of this study was to describe the morphology and functional involvement of the masseter muscles quantitatively. Ninety-eight patients with CFM who underwent three-dimensional computed tomography and surface electromyography were included. The mean action potential during maximum voluntary contraction in the intercuspal position was recorded. Asymmetry of the compound muscle action potential (ACMAP) was calculated as an indicator of functional involvement. Differences between the affected and unaffected sides, the correlation between morphology and function, and the relationship between ACMAP and the OMENS-Plus classification were assessed by paired t-test, Pearson correlation analysis, and Spearman correlation analysis. The masseter muscle was absent on the affected side in 11 patients. In the remaining 87 patients, the mean volumes of the affected and unaffected masseters were 5.22±2.47cm3 and 9.62±3.30cm3, respectively, with mean action potentials of 41.40±28.52uV and 73.78±45.90uV, respectively. Both morphology and the function of the masseter showed moderate correlation with the OMENS 'M' classification. No significant correlation was found between ACMAP and the OMENS-Plus soft tissue grading. A masseter function classification is proposed: type I, ACMAP

Background Postoperative infection is a complication of mandibular distraction osteogenesis (DO) in patients with hemifacial microsomia (HFM). The risk of surgical wound infection in DO is reported to be high due to the long duration of the distraction process. Treatment during the perioperative period is critical in combating infection. Aim This study aimed to evaluate the effectiveness of red-blue irradiation in the prevention of surgical wound infection after mandibular distraction. Methods In our single-centered, randomized clinical study, 118 patients diagnosed with HFM who had undergone DO between April 2016 and April 2018 were included. The patients were randomly divided into two groups: the experimental group received red-blue irradiation treatment and the control group received white-light irradiation. Results None of the infections occurring in this study resulted in serious complications. The postoperative infection rate during the 4 weeks after DO in the experimental group was 1.7%, whereas that in the control group was 13.6% (p = 0.016) (based on a modified NHSN wound infection criterion). The total social cost during the active period for the experimental group was 3386840 RMB, 5.12% higher than for the control group (3221882 RMB). Conclusions Red-blue irradiation is recommended as adjunctive therapy after mandibular distraction osteogeneis in HFM.

Purpose Augmented reality (AR) is considered to be a valuable tool in craniofacial surgery for preoperative design, intraoperative navigation, and postoperative assessment. Corrective surgery is necessary synostotic plagiocephaly for functional and aesthetic outcomes. Open calvarial reconstruction is a difficult classic surgical procedure with a high accuracy requirement. The purpose of this study was to introduce an AR system application in synostotic plagiocephaly surgery. Materials and methods Seven plagiocephaly patients (ages 6 months–24 months, average 16.7 months) were enrolled. Preoperative design was accomplished based on three-dimensional computed tomography (CT) data for patients with synostotic plagiocephaly. We completed the registration with the predefined markers through an image registration process preoperatively. Then, we overlaid the registration results into the surgical field to assist surgeons intraoperatively. CT scans were performed postoperatively. Intracranial volume was measured to judge the surgical outcomes. We performed a quantitative craniometric analysis between the planning of the reconstruction and post-operative results, and the main evaluation indicator was the intracranial volume asymmetry. Results We successfully applied the AR system in patients undergoing synostotic plagiocephaly, providing real-time navigational images of position and orientation information during open calvarial reconstruction surgery in 7 plagiocephaly patients within a span of 5 years. Good appearances were observed after the surgery. Cranial volume asymmetry was decreased from 27.87% to 16.57%, achieving precise intra-operative goals. No significant differences were found between planning and post-operative results. Conclusions The AR system can be applied to plagiocephaly procedures guiding to obtain reliable and accurate results via a precise osteotomy.

Human pluripotent stem cell (hPSC) density is an important factor in self-renewal and differentiation fates; however, the mechanisms through which hPSCs sense cell density and process this information in making cell fate decisions remain to be fully understood. One particular pathway that may prove important in density-dependent signaling in hPSCs is the Hippo pathway, which is regulated by cell-cell contact and mechanosensing through the cytoskeleton and has been linked to the maintenance of stem cell pluripotency. To probe regulation of Hippo pathway activity in hPSCs, we assessed whether Hippo pathway transcriptional activator YAP was differentially modulated by cell density. At higher cell densities, YAP phosphorylation and localization to the cytoplasm increased, which led to decreased YAP-mediated transcriptional activity. Furthermore, total YAP protein levels diminished at high cell density due to the phosphorylation-targeted degradation of YAP. Inducible shRNA knockdown of YAP reduced expression of YAP target genes and pluripotency genes. Finally, the density-dependent increase of neuroepithelial cell differentiation was mitigated by shRNA knockdown of YAP. Our results suggest a pivotal role of YAP in cell density-mediated fate decisions in hPSCs.

Hemifacial microsomia (HFM) is the second most common congenital craniofacial malformation. Although many sporadic and familial cases have been studied to explore the etiology and pathogenesis of HFM, no common understanding has been reached. We aimed to further probe into the etiology of HFM through studying monozygotic twins. Here, we report two cases of pairs of monozygotic twins discordant for HFM, and performed whole-exome sequencing (WES) and bioinformatics analysis to help determine the underlying molecular mechanisms. We identified 93 and 83, and 101 and 104 genes containing rare germline mutations in the twins of the two pairs, respectively. No positive gene candidates were found among the samples, and none of the analyses results revealed a clear intersection with previously reported gene candidates. The pathogenesis of HFM twin pairs does not appear to be related to single nucleotide variants or small insertions/deletions. Thus, HFM may be caused by structure variations, epigenetic alterations, and/or instability of short repeat sequences, which requires further investigation in a larger cohort with sequencing technology for verification.

Background Many researchers have studied the relationship between facial asymmetry and cranial base morphology, but they have failed to reach a consensus. In this study, we aimed to verify whether the cranial base is involved in hemifacial microsomia (HFM). Methods We included 66 patients with HFM who were treated at the Plastic and Reconstructive Surgery Department of Shanghai Ninth People's Hospital from January 2013 to October 2016. The patients were divided into three groups according to Pruzansky and OMENS classifications, separately. The controls were 20 patients diagnosed with mandibular angle hypertrophy but with no facial asymmetry. Angular and linear measurements of the cranial base were obtained for all patients. Results The two classification methods yielded similar results. The intersection angle between two planes showed differences in the severe group. In the moderate and severe groups, the middle and posterior cranial angles were significantly different and the CI P and S P lengths were shorter in the affected side. Landmarks such as the carotid canal and internal acoustic canal could be considered as references. Conclusions The cranial base is involved in hemifacial microsomia. This relationship supports the hypothesis of HFM pathogenesis and opens new avenues to classification methods.

Objective. Type 2 deiodinase (Dio2) is an enzyme responsible for the conversion of T4 to T3. The Thr92Ala polymorphism has been shown related to an increased risk for developing type 2 diabetes mellitus (T2DM). The aim of this study is to assess the association between this polymorphism and glycemic control in T2DM patients as marked by the HbA1C levels. Design and Methods. The terms “rs225014,” “thr92ala,” “T92A,” or “dio2 a/g” were used to search for eligible studies in the PubMed, Embase, and Cochrane databases and Google Scholar. A systematic review and meta-analysis of studies including both polymorphism testing and glycated hemoglobin (HbA1C) assays were performed. Results. Four studies were selected, totaling 2190 subjects. The pooled mean difference of the studies was 0.48% (95% CI, 0.18–0.77%), indicating that type 2 diabetics homozygous for the Dio2 Thr92Ala polymorphism had higher HbA1C levels. Conclusions. Homozygosity for the Dio2 Thr92Ala polymorphism is associated with higher HbA1C levels in T2DM patients. To confirm this conclusion, more studies of larger populations are needed.

An injectable hybrid hydrogel system was developed consisting of hyaluronic acid (HA) crosslinked by well-defined block copolymers of the cationic poly(2-aminoethyl methacrylate) (PAEM) and polyethylene glycol (PEG). Robust, shear-thinning hybrid hydrogel was produced by mixing HA and 4-arm star PEG-PAEM block copolymer at 1:1 charge ratio. The encapsulation and release of highly viable human mesenchymal stem cells in physiological media was demonstrated. After subcutaneous injection of the hybrid gel in mice, mild but resolvable inflammatory response was observed. This hybrid gel could serve as a model system for studying structure-function relationship of polyelectrolyte hydrogels and as a practical injectable biomaterial for medical applications.

A significant clinical need exists to differentiate human pluripotent stem cells (hPSCs) into cardiomyocytes, enabling tissue modeling for in vitro discovery of new drugs or cell-based therapies for heart repair in vivo. Chemical and mechanical microenvironmental factors are known to impact the efficiency of stem cell differentiation, but cardiac differentiation protocols in hPSCs are typically performed on rigid tissue culture polystyrene (TCPS) surfaces, which do not present a physiological mechanical setting. To investigate the temporal effects of mechanics on cardiac differentiation, we cultured human embryonic stem cells (hESCs) and their derivatives on polyacrylamide hydrogel substrates with a physiologically relevant range of stiffnesses. In directed differentiation and embryoid body culture systems, differentiation of hESCs to cardiac troponin T-expressing (cTnT+) cardiomyocytes peaked on hydrogels of intermediate stiffness. Brachyury expression also peaked on intermediate stiffness hydrogels at day 1 of directed differentiation, suggesting that stiffness impacted the initial differentiation trajectory of hESCs to mesendoderm. To investigate the impact of substrate mechanics during cardiac specification of mesodermal progenitors, we initiated directed cardiomyocyte differentiation on TCPS and transferred cells to hydrogels at the Nkx2.5/Isl1+ cardiac progenitor cell stage. No differences in cardiomyocyte purity with stiffness were observed on day 15. These experiments indicate that differentiation of hESCs is sensitive to substrate mechanics at early stages of mesodermal induction, and proper application of substrate mechanics can increase the propensity of hESCs to differentiate to cardiomyocytes.