Engineering three-dimensional (3D) vascularized constructs remains a challenge due to the inability to form rich microvessel networks. In this study we engineered a prevascularized 3D cell sheet construct for tissue regeneration using human bone marrow-derived mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells as cell sources. hMSCs were cultured to form a thick cell sheet, and human umbilical vein endothelial cells (HUVECs) were then seeded on the hMSCs sheet to form networks. The single prevascularized HUVEC/hMSC cell sheet was folded to form a 3D construct by a modified cell sheet engineering technique.In vitroresults indicated that the hMSCs cell sheet promoted the HUVECs cell migration to form networks in horizontal and vertical directions.In vivoresults showed that many blood vessels grew into the 3D HUVEC/hMSC cell sheet constructs after implanted in the subcutaneous pocket of immunodeficient mice. The density of blood vessels in the prevascularized constructs was higher than that in the nonprevascularized constructs. Immunohistochemistry staining further showed thatin vitropreformed human capillaries in the prevascularized constructs anastomosed with the host vasculature to form functional blood vessels. These results suggest the promising potential of this 3D prevascularized construct using hMSCs cell sheet as a platform for wide applications in engineering vascularized tissues.

There is a critical need for the management of large bone defects. The purpose of this study was to engineer a biomimetic periosteum and to combine this with a macroporous β-tricalcium phosphate (β-TCP) scaffold for bone tissue regeneration. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) were harvested and cultured in different culture media to form undifferentiated rBMSC sheets (undifferentiated medium (UM)) and osteogenic cell sheets (osteogenic medium (OM)). Simultaneously, rBMSCs were differentiated to induced endothelial-like cells (iECs), and the iECs were further cultured on a UM to form a vascularized cell sheet. At the same time, flow cytometry was used to detect the conversion rates of rBMSCs to iECs. The pre-vascularized cell sheet (iECs/UM) and the osteogenic cell sheet (OM) were stacked together to form a biomimetic periosteum with two distinct layers, which mimicked the fibrous layer and cambium layer of native periosteum. The biomimetic periostea were wrapped onto porous β-TCP scaffolds (BP/β-TCP) and implanted in the calvarial bone defects of rats. As controls, autologous periostea with β-TCP (AP/β-TCP) and β-TCP alone were implanted in the calvarial defects of rats, with a no implantation group as another control. At 2, 4, and 8 weeks post-surgery, implants were retrieved and X-ray, microcomputed tomography (micro-CT), histology, and immunohistochemistry staining analyses were performed. Flow cytometry results showed that rBMSCs were partially differentiated into iECs with a 35.1% conversion rate in terms of CD31. There were still 20.97% rBMSCs expressing CD90. Scanning electron microscopy (SEM) results indicated that cells from the wrapped cell sheet on the β-TCP scaffold apparently migrated into the pores of the β-TCP scaffold. The histology and immunohistochemistry staining results from in vivo implantation indicated that the BP/β-TCP and AP/β-TCP groups promoted the formation of blood vessels and new bone tissues in the bone defects more than the other two control groups. In addition, micro-CT showed that more new bone tissue formed in the BP/β-TCP and AP/β-TCP groups than the other groups. Inducing rBMSCs to iECs could be a good strategy to obtain an endothelial cell source for prevascularization. Our findings indicate that the biomimetic periosteum with porous β-TCP scaffold has a similar ability to promote osteogenesis and angiogenesis in vivo compared to the autologous periosteum. This function could result from the double layers of biomimetic periosteum. The prevascularized cell sheet served a mimetic fibrous layer and the osteogenic cell sheet served a cambium layer of native periosteum. The biomimetic periosteum with a porous ceramic scaffold provides a new promising method for bone healing.

Background: Only a few studies have used 3D cone-beam computed tomography (CBCT) analysis to evaluate the positional and morphological characteristics of the temporomandibular joint (TMJ) in adults with skeletal Class II. No studies have focused on the case of skeletal Class II with mandibular retrognathism in different vertical skeletal patterns. As a result, this study aimed to evaluate and compare the position and morphology of TMJ in adults with skeletal Class II with mandibular retrognathism in different vertical skeletal patterns to the position and morphology of TMJ in the normal Chinese adult population in three dimensions. Methods: This retrospective study analyzed CBCT images of 80 adult patients. Subjects with skeletal Class II with a normal sagittal position of the maxilla and mandibular retrognathism were classified according to the mandibular angle and facial height ratio into three groups of 20 subjects each: hypodivergent, normodivergent, and hyperdivergent groups, as well as a control group of 20 subjects. The following 3D measurements of TMJ were evaluated: (1) position, parameters, and inclination of the mandibular fossa; (2) position, parameters, and inclination of the mandibular condyle; (3) condyle centralization in their respective mandibular fossae; (4) anterior, posterior, superior, and medial joint spaces; and (5) 3D volumetric measurements of the TMJ spaces. Measurements were statistically analyzed by one-way ANOVA test, followed by Tukey’s post hoc test. Results: Significant differences were found in the hyperdivergent and hypodivergent groups compared with the normal group in the vertical and anteroposterior mandibular fossa position, vertical condylar inclination, and condylar width and length. The hyperdivergent group showed the significantly highest condylar inclination with the midsagittal plane; anterior and superior positioning of the condyle; smallest anterior, superior, and medial joint spaces; and largest volumetric total joint space relative to the two other groups. Conclusions: The condyle-fossa position and morphology differ with various vertical facial patterns in individuals with skeletal Class II mandibular retrognathism. These differences could be considered during TMD diagnosis and orthodontic treatment.

Objectives: This study aimed to assess whether functional mandibular advancement (FMA) will cause temporomandibular joint disorders (TMD) or have side effects on temporomandibular joint (TMJ) in adolescent patients.Methods: All searched databases, including PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trails and Scopus were searched. Gray literature and unpublished literature was also searched. Randomized controlled trails (RCT) and non-randomized studies of the effects of interventions (NRSI) directly observe the condition of adolescent patients’ TMJ after finishing treatment will be considered to include in our study. According to Cochrane Handbook, Cochrane Collaboration risk of bias tool was used to assess the quality of included RCTs, and Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool was used to assess the quality of included NRSIs.Result: Finally 18 researches were evaluated as eligible to include in this study. 5 of the studies were RCTs, 8 were NRSIs and 5 were systematic reviews. The data of RCTs and NRSIs were statistically pooled in meta-analysis. The number of samples under investigated among primary studies was 579 individuals,there were 80 patients who developed temporomandibular symptoms during or after treatment. But all the subjective symptoms disappeared during follow-up time. The statistical outcomes proved that patients received FMA didn’t show more tendency to develop temporomandibular symptoms [I² = 27%, OR = 0.54, 95%CI (0.33,0.87), p = 0.01].Conclusion: (1) TMJ symptoms may occur during the functional oral appliance wearing, but the symptoms will release or disappear after treatment or during the follow-up period. (2) Less convincing evidence indicates that slightly previous TMD and condyle-glenoid fossa relationship will be improved after treatment. (3) There is TMJ disc anterior displacement observed during treatment, but most of them will return to the normal position later. (4) Moderate evidence support that FMA will not have side effects on TMJ of adolescent patients.