Combined orthodontic and orthognathic treatment with 3D-printing technique offers a precise outcome: A case report of two years followup.

INTRODUCTION AND IMPORTANCE: Precision Medicine and evidence-based clinical treatment approach are proposed worldwide in medical science nowadays. Orthodontic first approach (OFA) and Computer-aided surgical simulation (CASS) combined 3D-printing technique offered more chances for the doctors to obey the principle of Precision Medicine in the orthodontic and orthognathic approach. CASE PRESENTATION: We reported a 20-year-old patient, with skeletal Class III relationship and asymmetric mandible, was treated by OFA. And with the CASS combined 3D-Printing Technique, the presurgery simulation and 3D-printed surgery guiding splint and stable splint offered the Combined Orthodontic and Orthognathic Treatment (COOT) a powerful and accurate guiding. The results exhibited that the patient had a perfect maxilla and mandible relationship and significant improvement in profile. CLINICAL DISCUSSION: There is still a debate between "surgery first" (SF) and conventional OFA. In this study, we analyzed the trend of different approaches in the COOT, which was a team work and required mainly the collaboration of orthodontist and Orthognathic surgeon. This study showed the precision of the CASS could offer for the OFA to evoke people immersing in saving time in COOT. CONCLUSION: All of these indicated that CASS was a powerful and precise method for COOT, which could offer the patient an esthetic and stable result.

The TiO2-µ implant residual is more toxic than the Al2O3-n implant residual via blocking LAP and inducing macrophage polarization.

Medical device residuals cause harmful effects and diseases in the human body, such as Particle Disease (PD), but the biological interaction of different types of particles is unclear. In this study, after a biological interaction screen between different particles, we aimed to explore the mechanism of the biological interaction between different types of particles, and the effect of a proteasome inhibitor on PD. Our studies showed that the titanium oxide microscale particle (Ti-µ) was more toxic than the aluminum oxide nanoscale particle (Al-n). Al-n activated LAP, attenuated the macrophage M1 polarization, inhibited the activator of the NF-κB pathway, and blocked the secretion of inflammatory factors and apoptosis in vitro, and also prevented the inflammation tissue disorder and aseptic loosening in vivo induced by Ti-µ. What is more, Bortezomib blocked apoptosis, secretion of inflammatory factors and the activation of the NF-κB pathway induced by TiO2 micro particles. Al-n-induced autophagy could play the function in the efficient clearance of dying cells by phagocytosis, and serves in dampening M1 polarization-related pro-inflammatory responses. While the Ti alloy medical implant and devices are applied worldwide, the toxicity of Ti-µ and its interaction with Al-n could be considered in the implant design, and Bortezomib was a potential therapeutic for PD.

Nanosized Alumina Particle and Proteasome Inhibitor Bortezomib Prevented inflammation and Osteolysis Induced by Titanium Particle via Autophagy and NF-κB Signaling.

Autophagy and NF-κB signaling are involving in the process of Particle Disease, which was caused by the particles released from friction interface of artificial joint, implant materials of particle reinforced composite, scaffolds for tissue engineering, or material for drug delivery. However, the biological interaction of different material particles and the mechanism of proteasome inhibitor, Bortezomib (BTZ), against Titanium (Ti) particle-induced Particle Disease remain unclear. In this study, we evaluated effect of nanosized Alumina (Al) particles and BTZ on reducing and treating the Ti particle-induced inflammatory reaction in MG-63 cells and mouse calvarial osteolysis model. We found that Al particles and BTZ could block apoptosis and NF- κB activation in osteoblasts in vitro and in a mouse model of calvarial resorption induced by Ti particles. We found that Al particles and BTZ attenuated the expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α). And Al prevented the IL-1ß expression induced by Ti via attenuating the NF- κB activation ß-TRCP and reducing the expression of Casepase-3. Expressions of autophagy marker LC3 was activated in Ti group, and reduced by Al and/not BTZ. Furthermore, the expressions of OPG were also higher in these groups than the Ti treated group. Collectively, nanosized Al could prevent autophagy and reduce the apoptosis, inflammatory and osteolysis induced by Ti particles. Our data offered a basic data for implant design when it was inevitable to use Ti as biomaterials, considering the outstanding mechanical propertie of Ti. What's more, proteasome inhibitor BTZ could be a potential therapy for wear particle-induced inflammation and osteogenic activity via regulating the activity of NF- κB signaling pathway.

The Proteasome Inhibitor Bortezomib Inhibits Inflammatory Response of Periodontal Ligament Cells and Ameliorates Experimental Periodontitis in Rats.

BACKGROUND: Periodontitis is a chronic inflammatory disease initiated by bacteria and their virulence factors. Bortezomib (BTZ) is the first proteasome inhibitor for clinical treatment of malignancies. Its anticancer activity is accompanied by an anti-inflammatory effect. However, there are few reports about its anti-inflammatory effect and underlying mechanism in periodontal disease, especially on human periodontal ligament cells (hPDLCs), which are considered a promising cell-based therapy for treating periodontitis. METHODS: hPDLCs were treated with lipopolysaccharide (LPS) and pretreated with BTZ. mRNA and protein levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1ß, IL-6, and IL-8 were determined. The anti-inflammatory mechanism of BTZ was studied. Further, experimental rat periodontitis was induced with ligature and LPS injection, and simultaneously and locally treated with BTZ (three injections/week). Four weeks after treatment, microcomputed tomography, immunohistochemical, and histopathologic analyses were performed. RESULTS: Bortezomib administration at safe concentrations (≤1 nM) inhibited production of proinflammatory cytokines in LPS-stimulated hPDLCs via nuclear factor (NF)-kappa B, p38/extracellular signal-regulated kinase, and mitogen-activated protein kinase/activator protein-1 pathways. Moreover, in the LPS and ligature-induced periodontitis rat model, BTZ suppressed expression of TNF-α, IL-1ß, IL-6, and IL-8, reduced the ratio of receptor activator of NF-κB ligand/osteoprotegerin, and prevented alveolar bone absorption. CONCLUSION: These findings demonstrate the anti-inflammatory activity of BTZ against periodontal inflammatory response and present BTZ as a promising therapy for periodontal disease.

SCFß-TRCP regulates osteoclastogenesis via promoting CYLD ubiquitination.

CYLD negatively regulates the NF-κB signaling pathway and osteoclast differentiation largely through antagonizing TNF receptor-associated factor (TRAF)-mediated K63-linkage polyubiquitination in osteoclast precursor cells. CYLD activity is controlled by IκB kinase (IKK), but the molecular mechanism(s) governing CYLD protein stability remains largely undefined. Here, we report that SCFß-TRCP regulates the ubiquitination and degradation of CYLD, a process dependent on prior phosphorylation of CYLD at Ser432/Ser436 by IKK. Furthermore, depletion of ß-TRCP induced CYLD accumulation and TRAF6 deubiquitination in osteoclast precursor cells, leading to suppression of RANKL-induced osteoclast differentiation. Therefore, these data pinpoint the IKK/ß-TRCP/CYLD signaling pathway as an important modulator of osteoclastogenesis.

Polyetheretherketone/nano-fluorohydroxyapatite composite with antimicrobial activity and osseointegration properties.

Lack of antibacterial activity and binding ability to natural bone tissue has significantly limited polyetheretherketone (PEEK) for many challenging dental implant applications. Here, we have developed a polyetheretherketone/nano-fluorohydroxyapatite (PEEK/nano-FHA) biocomposite with enhanced antibacterial activity and osseointegration through blending method. Smooth and rough surfaces of PEEK/nano-FHA biocomposites were also prepared. Our results showed that in vitro initial cell adhesion and proliferation on the nano-FHA reinforced PEEK composite were improved. In addition, higher alkaline phosphatase activity and cell mineralization were also detected in cells cultured on PEEK/nano-FHA biocomposites, especially for rough PEEK/nano-FHA surfaces. More importantly, the as-prepared PEEK/nano-FHA biocomposite could effectively prevent the proliferation and biofilm formation of bacterial. For in vivo test, the newly formed bone volume of PEEK/nano-FHA group was higher than that of bare PEEK group based on 3D microcomputed tomography and 2D histomorphometric analysis. These reports demonstrate that the developed PEEK/nano-FHA biocomposite has increased biocompatibility and antibacterial activity in vitro, and promoted osseointegration in vivo, which suggests that it holds potential to be applied as dental implant material in dental tissue engineering applications.

Nano-TiO2/PEEK bioactive composite as a bone substitute material: in vitro and in vivo studies.

BACKGROUND: Compared with titanium (Ti) and other metal implant materials, poly(ether-ether ketone) (PEEK) shows outstanding biomechanical properties. A number of studies have also reported attractive bioactivity for nano-TiO(2) (n-TiO(2)). METHODS: In this study, n-TiO(2)/PEEK nanocomposites were prepared, taking advantage of the unique properties of both PEEK polymer and n-TiO(2). The in vitro and in vivo bioactivity of these nanocomposites was assessed against a PEEK polymer control. The effect of surface morphology or roughness on the bioactivity of the n-TiO(2)/PEEK nanocomposites was also studied. n-TiO(2)/PEEK was successfully fabricated and cut into disks for physical and chemical characterization and in vitro studies, and prepared as cylindrical implants for in vivo studies. Their presence on the surface and dispersion in the composites was observed and analyzed by scanning and transmission electron microscopy and X-ray photoelectron spectroscopy. RESULTS: Bioactivity evaluation of the nanocomposites revealed that pseudopods of osteoblasts preferred to anchor at areas where n-TiO(2) was present on the surface. In a cell attachment test, smooth PEEK showed the lowest optical density value (0.56 ± 0.07) while rough n-TiO(2)/PEEK exhibited the highest optical density value (1.21 ± 0.34, P < 0.05). In in vivo studies, the percent bone volume value of n-TiO(2)/PEEK was approximately twice as large as that of PEEK (P < 0.05). Vivid three-dimensional and histologic images of the newly generated bone on the implants further supported our test results. CONCLUSION: Our study demonstrates that n-TiO(2) significantly improves the bioactivity of PEEK, especially if it has a rough composite surface. A n-TiO(2)/PEEK composite with a rough surface could be a novel alternative implant material for orthopedic and dental applications.