BMSCs-driven graphite oxide-grafted-carbon fibers reinforced polyetheretherketone composites as functional implants: in vivo biosafety and osteogenesis.

Mesenchymal stem cells (MSCs) are increasingly becoming a potential treatment approach for bone injuries due to the multi-lineage differentiation potential, ability to recognize damaged tissue sites and secrete bioactive factors that can enhance tissue repair. The aim of this work was to improve osteogenesis of carbon fibers reinforced polyetheretherketone (CF/PEEK) implants through bone marrow mesenchymal stem cells (BMSCs)-based therapy. Moreover, bioactive graphene oxide (GO) was introduced into CF/PEEK by grafting GO onto CF to boost the osteogenic efficiency of BMSCs. Subsequently, CF/PEEK was implanted into the symmetrical skull defect models of SD rats. Then in vivo biosafety and osteogenesis were evaluated. The results indicated that surface wettability of CF/PEEK was effectively improved by GO, which was beneficial for the adhesion of BMSCs. The pathological tissue sections stained with H&E showed no significant pathological change in the main organs including heart, liver, spleen, lung and kidney, which indicated no acute systemic toxicity. Furthermore, bone mineralization deposition rate of CF/PEEK containing GO was 2.2 times that of pure CF/PEEK. The X-ray test showed that the surface of CF/PEEK containing GO was obviously covered by more newly formed bone tissue than pure CF/PEEK after 8 weeks of implantation. This work demonstrated that GO effectively enhanced surface bioactivity of CF/PEEK and assisted BMSCs in accelerating differentiation into bone tissue, providing a feasible strategy for improving osteogenesis of PEEK and CF/PEEK.

Decoration with electronegative 2D materials based on chemical transition layers on CFR-PEEK implants for promoting osteogenesis.

Due to the unique lamellar structures, physicochemical and biological properties, electronegative two-dimensional (2D) materials have been explored for surface modification of carbon fibers reinforced polyetheretherketone (CFR-PEEK) composite. Deposition of electronegative 2D materials based on a porous surface created by concentrated H2SO4 has been studied to promote osteogenesis of CFR-PEEK. Generally, a porous layer will be pre-built on CFR-PEEK through severe corrosion of concentrated sulfuric acid to help the loading of 2D materials. However, the severe corrosion will greatly reduce surface mechanical strength, especially wear resistance and hardness, which increases the risk of collapse or even peeling of the bioactive coating by external force. Herein, instead of the severe corrosion, a mild corrosion by concentrated HNO3 was applied to modify the surface of CFR-PEEK to pre-create a dense transition layer for the further surface decoration of electronegative 2D materials (graphene oxide (GO) and black phosphorus (BP), representatively). The results indicated that hardness and wear resistance of the dense transition layer were markedly higher than those of the porous layer. Although GO and BP can be both loaded on these two transition layers, -SO3H on the porous transition layer showed moderate cytotoxicity, while -NO2 on the dense transition layer showed good cytocompatibility. The dense transition layer displayed higher mineralized deposition in vitro and new bone formation rate in vivo than the porous transition layer, moreover, GO and BP coatings improved osteogenesis. This work offers inspirations for the construction of electronegative 2D material coating on CFR-PEEK based on chemical transition layers.

Mechanical properties and osteogenesis of CFR-PEEK composite with interface strengthening by graphene oxide for implant application.

In this work, 1 wt% of graphite oxide (GO) was used to strengthen the interface of carbon fibers (CF) reinforced polyetheretherketone (CFR-PEEK) composites, so as to obtain sufficiently high mechanical properties and bioactive surfaces which are two fundamental requirements for orthopedic/dental implants. Concretely, aminated GO was grafted onto oxidized CF in aqueous solution in a mild and non-toxic manner, subsequently, the CF grafted by GO was used for injection molding to prepare CFR-PEEK implant. The dispersibility of CF in the composites were remarkably boosted. Mechanical tests indicated that the flexural strength, compressive strength and hardness of CFR-PEEK were increased by 51%, 46%, and 30%, respectively. Furthermore, the flexural modulus increased to 11.67 ± 0.20 GPa and the compression modulus increased to 6.12 ± 0.11 GPa, which both meet the elastic modulus of human bone (6-30 GPa). The wear resistance was slightly improved. In the in vitro cell evaluation, CFR-PEEK with interface strengthening by GO showed no cytotoxicity and exhibited significantly enhanced adhesion and proliferation of Bone marrow mesenchymal stem cells (BMSCs) on the surface. More importantly, osteogenesis-related protein expression in vitro and osteogenetic evaluation in vivo all disclosed greatly accelerated osteo-differentiation of BMSCs on the composites due to the additive effect of GO at the interface. Based on this scheme, the CFR-PEEK composites with the dual functions of mechanical enhancement and osteointegration promotion holds great potential as implants in orthopedic/dental applications.

AOSRV: Development and preliminary performance assessment of a new robotic system for autonomous percutaneous vertebroplasty.

BACKGROUND: Percutaneous vertebroplasty (PVP) is one of the most effective treatments for patients with vertebral fracture that need surgical treatment, and surgical robotics are promising tools to provide surgeons with improved precision, surgical efficiency and reduce radiation exposure. However, there are currently few robotics that are developed to help assist with PVP. METHODS: A new spinal surgical robotic system 'AOSRV' for autonomous vertebral puncture and bone cement injection was designed and customised in this study. To investigate its practical abilities and the advantages, we performed single-segment/double-segment PVP simulation surgeries on pig spinal specimens manually and using AOSRV. RESULTS: By contrast with the freehand group (FG) in single-segment (SS)/double-segment (DS) surgery, the robotic group (RG) was superior in the operation time (RGSS = 21.14 ± 4.11 min, FGSS = 33.17 ± 6.83 min; RGDS = 42.39 ± 7.31 min, FGDS = 62.86 ± 20.39 min), puncture adjustments (RGSS = 2.30 ± 1.77, FGSS = 14.86 ± 5.46; RGDS = 3.91 ± 1.76, FGDS = 20.00 ± 7.76), intraoperative fluoroscopies (RGSS = 4.10 ± 1.52, FGSS = 20.57 ± 5.44; RGDS = 7.82 ± 1.40, FGDS = 25.91 ± 7.23) and bone cement leakage rate (RGSS = 30%, FGSS = 71.4%; RGDS = 38.6%, FGDS = 83.3%). CONCLUSIONS: AOSRV was successfully developed and had a promising preliminary performance. An innovative attempt was made for the blank space of the autonomous vertebroplasty surgical robotics, and it may shed a light on more promising applications in the future.

Application of interferon response-related gene array to the antiviral treatment outcome in chronic hepatitis C.

BACKGROUND/AIMS: It has been known that viral factors such as genotype and viral load have a major influence on the outcome of antiviral treatment. Nevertheless, researchers have become increasingly aware that host genetic factors can modulate the response to antiviral treatment. The underlying mechanisms for the varying virologic response rates to IFNalpha-based antiviral therapy are unknown. METHODOLOGY: RNA was isolated from peripheral blood monocytes from treatment-naïve patients with chronic hepatitis C before and at the end of treatment. Gene expression was measured using SuperArray microarrays and compared to that of healthy controls. RESULTS: Ten patients were classified as rapid responders (RRs) and seven patients as non-RRs according to the serum HCV RNA level after 4 weeks of treatment in 17 patients with CHC. Compared with healthy controls, nine and eighteen different expression genes were found significantly in patients with RR and N-RR, respectively. Five different expression genes were found between the patients with RR and N-RR. Two genes that were down-regulated were found between HCV genotype 1b and genotype 2a. Seven different expression genes that were all down-regulated were found between the patients with ETVR and N-ETVR. CONCLUSIONS: (1) The down-regulation of some IFN response-related genes are associated with null response to treat with interferon. (2) It should be HCV genotype 1b is more successful in inducing the down-regulation of IFN response-related genes than HCV genotype 2a, thus contribute to the resistance to IFN.

Biomimetic Domain-Active Electrospun Scaffolds Facilitating Bone Regeneration Synergistically with Antibacterial Efficacy for Bone Defects.

To improve bone regeneration in oral microenvironment, we generated a novel biodegradable, antibacterial, and osteoconductive electrospun PLGA/PCL membrane as an ideal osteogenic scaffold. The novel three-layer membranes were structured with serial layers of electrospun chlorhexidine-doped-PLGA/PCL (PPC), PLGA/PCL (PP), and ß-tricalcium phosphate-doped-PLGA/PCL (PPß). To characterize osteoconductive properties of these membranes, MC3T3-E1 (MC) cultures were seeded onto the membranes for 14 days for evaluation of cell proliferation, morphology and gene/protein expression. In addition, MC cells were cultured onto different surfaces of the three-layer membranes, PPC layer facing MC cells (PPß-PP-PPC) and PPß layer facing MC cells (PPC-PP-PPß) to evaluate surface-material effects. Membrane properties and structures were evaluated. Antibacterial properties against Streptococcus mutans and Staphylococcus aureus were determined. Scanning electron microscope demonstrated smaller interfiber spaces of PPC and PPß-PP-PPC compared to PPß, PPC-PP-PPß, and PP. PPC and PPß-PP-PPC exhibited hydrophilic property. The three-layer membranes (PPC-PP-PPß and PPß-PP-PPC) demonstrated significantly higher Young's modulus (94.99 ± 4.03 MPa and 92.88 ± 4.03 MPa) compared to PP (48.76 ± 18.15 MPa) or PPC (7.92 ± 3.97 MPa) (p < 0.05). No significant difference of cell proliferation was found among any groups at any time point (p > 0.05). Higher expression of integrins were detected at 12 h of cultures on PPC-PP-PPß compared to the controls. Promoted osteoconductive effects of PPC-PP-PPß were revealed by alkaline phosphatase assays and Western blot compared with the controls at 7 and 14 days. PPC, PPC-PP-PPß and PPß-PP-PPC exhibited a significantly wider antibacterial zone against the tested bacteria compared to PP and PPß (p < 0.05). These results suggested that the three-layer electrospun membranes demonstrated superior properties: higher strength, better cell adhesion, and promoted osteoconductive properties compared to single-layer membrane: however, antibacterial properties were exhibited in three-layer electrospun membranes and chlorhexidine-doped single-layer membrane. We concluded that the novel three-layer membranes could be used as a biocompatible scaffold for intraoral bone regeneration due to its enhanced osteoconductive activity and antibacterial effect.