Lixia Mao

Akermanite bioceramics promote osteogenesis, angiogenesis and suppress osteoclastogenesis for osteoporotic bone regeneration.

It is a big challenge for bone healing under osteoporotic pathological condition with impaired angiogenesis, osteogenesis and remodeling. In the present study, the effect of Ca, Mg, Si containing akermanite bioceramics (Ca2MgSi2O7) extract on cell proliferation, osteogenic differentiation and angiogenic factor expression of BMSCs derived from ovariectomized rats (BMSCs-OVX) as well as the expression of osteoclastogenic factors was evaluated. The results showed that akermanite could enhance cell proliferation, ALP activity, expression of Runx2, BMP-2, BSP, OPN, OCN, OPG and angiogenic factors including VEGF and ANG-1. Meanwhile, akermanite could repress expression of osteoclastogenic factors including RANKL and TNF-α. Moreover, akermanite could activate ERK, P38, AKT and STAT3 signaling pathways, while crosstalk among these signaling pathways was evident. More importantly, the effect of akermanite extract on RANKL-induced osteoclastogenesis was evaluated by TRAP staining and real-time PCR assay. The results showed that akermanite could suppress osteoclast formation and expression of TRAP, cathepsin K and NFATc1. The in vivo experiments revealed that akermanite bioceramics dramatically stimulated osteogenesis and angiogenesis in an OVX rat critical-sized calvarial defect model. All these results suggest that akermanite bioceramics with the effects of Mg and Si ions on osteogenesis, angiogenesis and osteoclastogenesis are promising biomaterials for osteoporotic bone regeneration.

Changes in condylar and joint disc positions after bilateral sagittal split ramus osteotomy for correction of mandibular prognathism.

The effect of combined orthodontic and orthognathic treatment was studied retrospectively in 24 patients with skeletal class III malocclusions with mandibular hyperplasia, particularly the effect on temporomandibular joint (TMJ) disc position. The patients underwent preoperative orthodontic treatment, orthognathic surgery, and postoperative orthodontic treatment. The patients were studied clinically, radiographically with lateral cephalometric radiograph and MRI to locate the position of the TMJ disc in relation to the glenoid fossa. One patient had less pain after treatment, one lost abnormal joint clicking sounds after treatment. There were no TMJ symptoms in 20 of the 24 preoperatively and postoperatively. 48 sagittal MRI images showed that the disc length before treatment was 3.040-12.928 (mean 8.289+/-2.028) and after treatment was 3.699-11.589 (mean 8.097+/-1.966); results were not significant (p>0.05). Maximum disc displacement before treatment was 6.090 (mean 1.383), after treatment it was 11.931 (mean 2.193); results were not significant (p>0.05). The results suggest that combined orthodontic and orthognathic treatment (including bilateral SSRO and rigid internal fixation) can be used safely to correct skeletal class III malocclusion with mandibular hyperplasia without causing additional TMJ symptoms.

The synergistic effects of Sr and Si bioactive ions on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration

Bioactive ions released from bioceramics play important roles in bone regeneration; however, it is unclear how each ionic composition in complex bioceramics exerts its specific effect on bone regeneration. The aim of this study is to elucidate the functional effects of Sr and Si ions in bioceramics on the regeneration of osteoporotic bone. A model bioceramic with Sr- and Si-containing components (SMS) was successfully fabricated and the effects of ionic products from SMS bioceramics on the osteogenic, osteoclastic and angiogenic differentiation of rBMSCs-OVX and RANKL-induced osteoclasts were investigated. The results showed that SMS bioceramics could enhance ALP activity and expression of Col 1, OCN, Runx2, and angiogenic factors including VEGF and Ang-1. SMS bioceramics not only rebalanced the OPG/RANKL ratio of rBMSCs-OVX at early stage, but also repressed RANKL-induced osteoclast formation and expression of TRAP, DC-STAMP, V-ATPase a3, and NFATc1. The synergistic effects of Sr and Si ions were further investigated as compared with those of similar concentrations of Sr and Si ions alone. Sr and Si ions possessed synergistic effects on osteogenesis, osteoclastogenesis, and angiogenesis, attributed to the dominant effects of Sr ions on enhancing angiogenesis and repressing osteoclastogenesis, and the dominant effects of Si ions on stimulating osteogenesis. The in vivo study using critical-size mandibular defects of OVX rat models showed that SMS bioceramics could significantly enhance bone formation and mineralization compared with β-TCP bioceramics. Our results are the first to elucidate the specific effect of each ion from bioceramics on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration, paving the way for the design of functional biomaterials with complex compositions for tissue engineering and regenerative medicine. STATEMENT OF SIGNIFICANCE Bioactive ions released from bioceramics play important roles for bone regeneration; however, it is unclear how each of ionic compositions in complex bioceramics exerts its specific effect on bone regeneration. The aim of present study is to elucidate the functional effects of Sr and Si ions in complex bioceramics on the regeneration of osteoporotic bone. A model bioceramic with Sr and Si-containing components (SMS) was successfully fabricated and the effects of ionic products from SMS bioceramics on the osteogenic, osteoclastic and angiogenic differentiation of rBMSCs-OVX and RANKL-induced osteoclasts were investigated. The results showed that SMS bioceramics could enhance ALP activity and expression of Col 1, OCN, Runx2 and angiogenic factors including VEGF and Ang-1. SMS bioceramics not only rebalanced the ratio of OPG/RANKL of OVX-BMSCs at early stage, but also repressed RANKL-induced osteoclast formation and expression of TRAP, DC-STAMP, V-ATPase a3, and NFATc1. The synergistic effects of Sr and Si ions were further investigated as compared with the similar concentration of Sr and Si ions alone. It was found that Sr and Si ions possessed synergistic effects on osteogenesis, osteoclastogenesis and angiogenesis, attributed to the dominant effects of Sr ions on enhancing angiogenesis and repressing osteoclastogenesis, and the dominant effects of Si ions on stimulating osteogenesis. The in vivo study using critical-size mandibular defects of OVX rat models showed that SMS bioceramics could significantly enhance bone formation and mineralization as compared with β-TCP bioceramics. It is suggested that SMS bioceramics may be a promising biomaterial for osteoporotic bone regeneration. To our knowledge, this is the first time to elucidate the specific effect of each ion from bioceramics on osteogenesis, osteoclastogenesis and angiogenesis for osteoporotic bone regeneration, paving the way to design functional biomaterials with complex compositions for tissue engineering and regenerative medicine.

The synergetic effect of nano-structures and silicon-substitution on the properties of hydroxyapatite scaffolds for bone regeneration

Control over the morphology and chemical composition of hydroxyapatite (HAp) bioceramic scaffolds is of great importance for their applications. In the present study, Si-substituted HAp bioceramic scaffolds with controllable morphologies (nanosheets and nanorods) were fabricated via hydrothermal treatment of calcium silicate scaffolds as precursors in NaH2PO4 and Na3PO4 aqueous solutions, respectively. Moreover, the effects of surface morphologies and Si substitution on cell attachment, proliferation, and osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) were systematically investigated in vitro. The results showed that nano-topography surfaces could enhance cell attachment, cell proliferation, alkaline phosphatase (ALP) activity, and mRNA expression levels of collagen 1 (COL1), bone morphogenetic protein 2 (BMP-2), bone sialoprotein (BSP) and osteopontin (OPN). Moreover, the Si substitution could further promote cell proliferation and osteogenic differentiation, while Si-substituted bioceramics with a nanorod surface possessed the highest stimulatory effect. More importantly, the in vivo rat critical-sized calvarial defect model confirmed that HAp bioceramic scaffolds with nanosheet and nanorod surfaces showed definitive bone regeneration as compared with control HAp bioceramic scaffolds with a traditional smooth surface. Moreover, Si substitution could synergistically enhance bone regeneration and mineralization, while Si-substituted HAp bioceramic scaffolds with a nanorod surface achieved the best bone repair ability. The present study suggests that the modification of the surface morphology and Si substitution on the HAp bioceramic scaffold may be an effective synergistic strategy to improve its clinical performance.

Europium-Containing Mesoporous Bioactive Glass Scaffolds for Stimulating in Vitro and in Vivo Osteogenesis

Bone tissue engineering offers a possible strategy for regenerating large bone defects, in which how to design beneficial scaffolds for accelerating bone formation remains significantly challenging. Europium, as an important rare earth element, has been used as a solid-state lighting material. However, there are few reports on whether Eu can be used for labeling bone tissue engineering scaffolds, and its biological effect on bone cells and bone tissue regeneration is unknown. In this study, we incorporated Eu into mesoporous bioactive glass (Eu-MBG) scaffolds by an in situ cotemplate method to achieve a bifunctional biomaterial with biolabeling and bone regeneration. The prepared Eu-MBG scaffolds have highly interconnective large pores (300-500 μm), a high specific surface area (140-290 m(2)/g), and well-ordered mesopores (5 nm) as well as uniformly distributed Eu. The incorporation of 2-5 mol % Eu into MBG scaffolds gives them a luminescent property. The in vitro degradation of Eu-MBG scaffolds has a functional effect on the change of the luminescence intensity. In addition, Eu-MBG can be used for labeling bone marrow stromal cells (BMSCs) in vitro and still presents a distinct luminescence signal in deep bone tissues in vivo to label new bone tissue via release of Eu ions. Furthermore, the incorporation of different contents of Eu (1, 2, and 5 mol %) into MBG scaffolds significantly enhances the osteogenic gene expression of BMSCs in the scaffolds. The Eu- and Si-containing ionic products released from Eu-MBG scaffolds distinctly promote the osteogenic differentiation of BMSCs. Critically sized femur defects in ovariectomized (OVX) rats are created to simulate an osteoporotic phenotype. The results show that Eu-MBG scaffolds significantly stimulate new bone formation in osteoporotic bone defects when compared to MBG scaffolds alone and Eu may be involved in the acceleration of bone regeneration in OVX rats. Our study for the first time reports that the incorporation of the rare earth element Eu into bioscaffolds has the ability to accelerate bone regeneration in vivo, and thus, the prepared Eu-MBG scaffolds possess bifunctional properties with biolabeling and bone regeneration.

Effect of micro-nano-hybrid structured hydroxyapatite bioceramics on osteogenic and cementogenic differentiation of human periodontal ligament stem cell via Wnt signaling pathway

The surface structure of bioceramic scaffolds is crucial for its bioactivity and osteoinductive ability, and in recent years, human periodontal ligament stem cells have been certified to possess high osteogenic and cementogenic differential ability. In the present study, hydroxyapatite (HA) bioceramics with micro-nano-hybrid surface (mnHA [the hybrid of nanorods and microrods]) were fabricated via hydrothermal reaction of the α-tricalcium phosphate granules as precursors in aqueous solution, and the effects of mnHA on the attachment, proliferation, osteogenic and cementogenic differentiations of human periodontal ligament stem cells as well as the related mechanisms were systematically investigated. The results showed that mnHA bioceramics could promote cell adhesion, proliferation, alkaline phosphatase (ALP) activity, and expression of osteogenic/cementogenic-related markers including runt-related transcription factor 2 (Runx2), ALP, osteocalcin (OCN), cementum attachment protein (CAP), and cementum protein (CEMP) as compared to the HA bioceramics with flat and dense surface. Moreover, mnHA bioceramics stimulated gene expression of low-density lipoprotein receptor-related protein 5 (LRP5) and β-catenin, which are the key genes of canonical Wnt signaling. Moreover, the stimulatory effect on ALP activity and osteogenic and cementogenic gene expression, including that of ALP, OCN, CAP, CEMP, and Runx2 of mnHA bioceramics could be repressed by canonical Wnt signaling inhibitor dickkopf1 (Dkk1). The results suggested that the HA bioceramics with mnHA could act as promising grafts for periodontal tissue regeneration.

The surgery-first approach in orthognathic surgery: a retrospective study of 50 cases

The surgery-first approach (SFA), without presurgical orthodontic treatment, has become favoured in the treatment of dentomaxillofacial deformities. This approach has been applied in our institution since 2012. The purpose of this study was to report our experience with the SFA for skeletal malocclusion. Fifty patients with skeletal malocclusions were enrolled in this study (11 bimaxillary protrusion, 27 skeletal class III malocclusion, and 12 facial asymmetry). After orthognathic-orthodontic consultation, suitability for SFA was determined and a treatment plan drawn up. Patients then underwent orthognathic surgery, which included Le Fort I maxillary osteotomy, bilateral sagittal split ramus osteotomy, subapical osteotomy, and genioplasty. Postoperative orthodontic treatment was started after a healing period of 2 weeks. The mean postoperative orthodontic treatment duration was 14.9 months, which is shorter than that of traditional joint orthognathic-orthodontic treatment. In the bimaxillary protrusion group, this was about 19 months, which was longer than for the other groups. After joint orthognathic-orthodontic treatment, a good facial profile and ideal occlusion were achieved. With the advantages of earlier improvements in patient facial aesthetics and dental function, the reduction in difficulty and treatment duration of orthodontic management, and increasing patient acceptance, SFA is regarded as an ideal and valuable alternative for this potentially complicated procedure.