Surface-Engineered Titanium with Nanoceria to Enhance Soft Tissue Integration Via Reactive Oxygen Species Modulation and Nanotopographical Sensing.

The design of implantable biomaterials involves precise tuning of surface features because the early cellular fate on such engineered surfaces is highly influenced by many physicochemical factors [roughness, hydrophilicity, reactive oxygen species (ROS) responsiveness, etc.]. Herein, to enhance soft tissue integration for successful implantation, Ti substrates decorated with uniform layers of nanoceria (Ce), called Ti@Ce, were optimally developed by a simple and cost-effective in situ immersion coating technique. The characterization of Ti@Ce shows a uniform Ce distribution with enhanced roughness (∼3-fold increase) and hydrophilicity (∼4-fold increase) and adopted ROS-scavenging capacity by nanoceria coating. When human gingival fibroblasts were seeded on Ti@Ce under oxidative stress conditions, Ti@Ce supported cellular adhesion, spreading, and survivability by its cellular ROS-scavenging capacity. Mechanistically, the unique nanocoating resulted in higher expression of amphiphysin (a nanotopology sensor), paxillin (a focal adhesion protein), and cell adhesive proteins (collagen-1 and fibronectin). Ti@Ce also led to global chromatin condensation by decreasing histone 3 acetylation as an early differentiation feature. Transcriptome analysis by RNA sequencing confirmed the chromatin remodeling, antiapoptosis, antioxidant, cell adhesion, and TGF-ß signaling-related gene signatures in Ti@Ce. As key fibroblast transcription (co)factors, Ti@Ce promotes serum response factor and MRTF-α nucleus localization. Considering all of this, it is proposed that the surface engineering approach using Ce could improve the biological properties of Ti implants, supporting their functioning at soft tissue interfaces and utilization as a bioactive implant for clinical conditions such as peri-implantitis.

Effects of ultraviolet weathering aging on the color stability and biocompatibility of various computer-aided design and computer-aided manufacturing glass-ceramic materials.

OBJECTIVES: This study assessed the changes in color stability and biocompatibility of computer-aided design and computer-aided manufacturing (CAD-CAM) glass-ceramics after ultraviolet weathering (UW) aging. METHODS: A total of 300 plate-shaped specimens (12.0 × 14.0 × 1.5 mm3) were prepared using a leucite-reinforced glass-ceramic (IPS Empress CAD; E), a lithium disilicate (IPS e.max CAD; M), and two zirconia-reinforced lithium silicate (Celtra Duo; C, Vita Suprinity; V) glass-ceramics. Specimens were divided into three groups (n = 25, each), subjected to water storage at 37 °C for 24 h (control group), or UW aging at 150 kJ/m2 (first-aged group) or 300 kJ/m2 (second-aged group). The color stability, mechanical and surface properties, and biocompatibility of the CAD-CAM glass-ceramics were investigated experimentally, followed by statistical analysis. RESULTS: The brightness and redness or greenness were reduced in all groups after aging. After the first aging, V exhibited the largest color change and E exhibited the smallest color change. After the second aging, E exhibited the highest nanoindentation hardness and Young's modulus. The surface roughness was the highest for V after the first aging. Furthermore, the hydrophilicity of the materials increased after aging process. The cell proliferation/viability of human gingival fibroblasts was the highest in E before and after aging. Almost all cells survived for all groups based on a live/dead assay. CONCLUSIONS: Leucite-reinforced glass-ceramic exhibit the highest color stability and biocompatibility after aging. The color stability and biocompatibility of CAD-CAM glass-ceramics depend on the aging process and material type. CLINICAL SIGNIFICANCE: Various CAD-CAM glass-ceramics exhibit adequate color stability after UW aging. The leucite-reinforced glass-ceramics exhibit the highest color stability, cell proliferation, and viability after aging. The color stability, mechanical and surface properties, and biocompatibility of the glass-ceramics depend on the aging process and material type.

Cyclic Stretch Promotes Cellular Reprogramming Process through Cytoskeletal-Nuclear Mechano-Coupling and Epigenetic Modification.

Advancing the technologies for cellular reprogramming with high efficiency has significant impact on regenerative therapy, disease modeling, and drug discovery. Biophysical cues can tune the cell fate, yet the precise role of external physical forces during reprogramming remains elusive. Here the authors show that temporal cyclic-stretching of fibroblasts significantly enhances the efficiency of induced pluripotent stem cell (iPSC) production. Generated iPSCs are proven to express pluripotency markers and exhibit in vivo functionality. Bulk RNA-sequencing reveales that cyclic-stretching enhances biological characteristics required for pluripotency acquisition, including increased cell division and mesenchymal-epithelial transition. Of note, cyclic-stretching activates key mechanosensitive molecules (integrins, perinuclear actins, nesprin-2, and YAP), across the cytoskeletal-to-nuclear space. Furthermore, stretch-mediated cytoskeletal-nuclear mechano-coupling leads to altered epigenetic modifications, mainly downregulation in H3K9 methylation, and its global gene occupancy change, as revealed by genome-wide ChIP-sequencing and pharmacological inhibition tests. Single cell RNA-sequencing further identifies subcluster of mechano-responsive iPSCs and key epigenetic modifier in stretched cells. Collectively, cyclic-stretching activates iPSC reprogramming through mechanotransduction process and epigenetic changes accompanied by altered occupancy of mechanosensitive genes. This study highlights the strong link between external physical forces with subsequent mechanotransduction process and the epigenetic changes with expression of related genes in cellular reprogramming, holding substantial implications in the field of cell biology, tissue engineering, and regenerative medicine.

Long-term cumulative survival and mechanical complications of single-tooth Ankylos Implants: focus on the abutment neck fractures.

PURPOSE: To evaluate the cumulative survival rate (CSR) and mechanical complications of single-tooth Ankylos® implants. MATERIALS AND METHODS: This was a retrospective clinical study that analyzed 450 single Ankylos® implants installed in 275 patients between December 2005 and December 2012. The main outcomes were survival results CSR and implant failure) and mechanical complications (screw loosening, fracture, and cumulative fracture rate [CFR]). The main outcomes were analyzed according to age, sex, implant length or diameter, bone graft, arch, and position. RESULTS: The 8-year CSR was 96.9%. Thirteen (2.9%) implants failed because of early osseointegration failure in 3, marginal bone loss in 6, and abutment fracture in 4. Screw loosening occurred in 10 implants (2.2%), and 10 abutment fractures occurred. All abutment fractures were located in the neck, and concurrent screw fractures were observed. The CSR and rate of screw loosening did not differ significantly according to factors. The CFR was higher in middle-aged patients (5.3% vs 0.0% in younger and older patients); for teeth in a molar position (5.8% vs 0.0% for premolar or 1.1% for anterior position); and for larger-diameter implants (4.5% for 4.5 mm and 6.7% for 5.5 mm diameter vs 0.5% for 3.5 mm diameter) (all P<.05). CONCLUSION: The Ankylos® implant is suitable for single-tooth restoration in Koreans. However, relatively frequent abutment fractures (2.2%) were observed and some fractures resulted in implant failures. Middle-aged patients, the molar position, and a large implant diameter were associated with a high incidence of abutment fracture.

Comparable efficacy of silk fibroin with the collagen membranes for guided bone regeneration in rat calvarial defects.

PURPOSE: Silk fibroin (SF) is a new degradable barrier membrane for guided bone regeneration (GBR) that can reduce the risk of pathogen transmission and the high costs associated with the use of collagen membranes. This study compared the efficacy of SF membranes on GBR with collagen membranes (Bio-Gide®) using a rat calvarial defect model. MATERIALS AND METHODS: Thirty-six male Sprague Dawley rats with two 5 mm-sized circular defects in the calvarial bone were prepared (n=72). The study groups were divided into a control group (no membrane) and two experimental groups (SF membrane and Bio-Gide®). Each group of 24 samples was subdivided at 2, 4, and 8 weeks after implantation. New bone formation was evaluated using microcomputerized tomography and histological examination. RESULTS: Bone regeneration was observed in the SF and Bio-Gide®-treated groups to a greater extent than in the control group (mean volume of new bone was 5.49 ± 1.48 mm(3) at 8 weeks). There were different patterns of bone regeneration between the SF membrane and the Bio-Gide® samples. However, the absolute volume of new bone in the SF membrane-treated group was not significantly different from that in the collagen membrane-treated group at 8 weeks (8.75 ± 0.80 vs. 8.47 ± 0.75 mm(3), respectively, P=.592). CONCLUSION: SF membranes successfully enhanced comparable volumes of bone regeneration in calvarial bone defects compared with collagen membranes. Considering the lower cost and lesser risk of infectious transmission from animal tissue, SF membranes are a viable alternative to collagen membranes for GBR.

Evaluation of a novel paediatric self-inflating bag to improve accuracy of tidal volumes delivered during simulated advanced paediatric resuscitation.

OBJECTIVE: The aim of the study is to compare the accuracy of manually delivered target tidal volumes (TVs) with the conventional paediatric self-inflating bags (CPBs) versus the novel paediatric self-inflating bags (NPBs) during simulated advanced paediatric resuscitation. METHODS: Before the trial begun, four target TV ranges were established using the Broselow™ Tape as a reference: 36-70 ml for 6-10 kg, 60-105 ml for 10-15 kg, 90-168 ml for 15-24 kg and 144-210 ml for 24-30 kg. An NPB with four surface marks matching the target TV ranges was prepared. Senior medical students (N=73) were enrolled. After 1 week of training in TV delivery with both CPB and NPB, subjects participated in a test simulation. Using the CPB and NPB in a random cross-over design, participants delivered 10 ventilations to test lungs connected to gas flow analysers for the randomly assigned target TV ranges. RESULTS: Each of the 730 values for TV and peak inspiratory pressures (PIPs) delivered by CPB and NPB were analysed. The proportion of accurate TV delivery was higher with NPB than with CPB: 84.2% versus 45.9% for 36-70 ml, 93.2% versus 42.7% for 60-105 ml, 96.0% versus 70.3% for 90-168 ml and 91.2% versus 62.6% for 144-210 ml, respectively (all p<0.0001). Compared with NPB, CPB delivery was more varied and was more frequently out of range. There were no significant differences in PIP between the CPB and NPB. CONCLUSIONS: NPB is useful as a ventilation device for the accurate delivery of TV to small children of varying weights.

Novel target volume marked adult bag to deliver accurate tidal volume for paediatric and adolescent resuscitation.

AIM: To overcome limitations of inaccurate tidal volume (TV) delivery by conventional selfinflating paediatric and adult bags during paediatric and adolescent resuscitation, we designed a novel target volume marked bag (TVMB) with four compression points marked on an adult bag surface. The aim of this study was to evaluate the TVMB in delivering preset TV. METHODS: Fifty-three subjects (28 doctors, 17 nurses, 8 paramedics) participated in this simulation trial. TVMB, paediatric bag and adult bag were connected to a gas flow analyser for measuring TV and peak inspiratory pressure (PIP). In a random cross-over setting, participants delivered 10 ventilations using the adult bag, paediatric bag or TVMB in each of four target volume ranges (100-200 ml, 200-300 ml, 300-400 ml, 400-500 ml). We compared TV and PIP for the adult bag, paediatric bag and TVMB in each subject. RESULTS: Compared with the paediatric bag, TVMB showed higher rates of accurate TV delivery in the 200-300 ml target volume range (87-90% versus 32-35%; p < 0.05). Compared with the adult bag, TVMB showed higher rates of accurate TV delivery in all target volume ranges (75-90% versus 45-50%; p < 0.05). The frequency of too high or low TV delivery was higher with the adult bag than TVMB (20-30% versus 0-5%; p < 0.05). There was no significant difference in PIP between the paediatric bag and TVMB (within 5 cm H(2)O; p < 0.05). CONCLUSIONS: TVMB could deliver accurate TV in various target volume ranges for paediatric and adolescent resuscitation.

NAD-dependent malate dehydrogenase protects against oxidative damage in Escherichia coli K-12 through the action of oxaloacetate.

Reactive oxygen species including hydrogen peroxide (H(2)O(2)) and hydroxyl radical (OH) can be generated by ionizing radiation and has the potential to induce diseases. We provide the evidence that NAD-dependent malate dehydrogenase (MDH) is involved in the antioxidant role in preventing H(2)O(2) or γ-radiation-induced damage in Escherichia coli through the action of oxaloacetate. The E. colimdh mutant strain defective in MDH activity was more sensitive to H(2)O(2) or γ-radiation than was the wild type strain, when challenged in the exponential growth phase. The mdh mutant cells pretreated with oxaloacetate (2.5 mM), a product of NAD-dependent MDH activity, prior to H(2)O(2) treatment or γ-irradiation are resistant to H(2)O(2) or γ-radiation-induced damage, so cell survivability is restored to similar levels with the wild type. The SOS induction of umu'-'lacZ fusion gene by H(2)O(2) is significantly repressed by pretreatment of oxaloacetate in a dose-dependent way. These results indicate that oxaloacetate effectively protects E. coli cells against damage caused by oxidative stress. Oxaloacetate strongly prevented the DNA strand breaks by OH in a metal-catalyzed oxidation (MCO) system that generated H(2)O(2) as a mediator. By contrast, the prevention of DNA damage by oxaloacetate in an γ-irradiation system that directly generates OH from H(2)O in vitro was far less than that in an MCO system. Our results demonstrated that oxaloacetate, metabolite of NAD-dependent MDH action, plays a role as an antioxidant, possibly by scavenging H(2)O(2).