ROR2 Downregulation Activates the MSX2/NSUN2/p21 Regulatory Axis and Promotes Dental Pulp Stem Cell Senescence.

Cellular senescence severely limits the research and the application of dental pulp stem cells (DPSCs). A previous study conducted by our research group revealed a close implication of ROR2 in DPSC senescence, although the mechanism underlying the regulation of ROR2 in DPSCs remains poorly understood so far. In the present study, it was revealed that the expression of the ROR2-interacting transcription factor MSX2 was increased in aging DPSCs. It was demonstrated that the depletion of MSX2 inhibits the senescence of DPSCs and restores their self-renewal capacity, and the simultaneous overexpression of ROR2 enhanced this effect. Moreover, MSX2 knockdown suppressed the transcription of NOP2/Sun domain family member 2 (NSUN2), which regulates the expression of p21 by binding to and causing the 5-methylcytidine methylation of the 3'- untranslated region of p21 mRNA. Interestingly, ROR2 downregulation elevated the levels of MSX2 protein, and not the MSX2 mRNA expression, by reducing the phosphorylation level of MSX2 and inhibiting the RNF34-mediated MSX2 ubiquitination degradation. The results of the present study demonstrated the vital role of the ROR2/MSX2/NSUN2 axis in the regulation of DPSC senescence, thereby revealing a potential target for antagonizing DPSC aging.

Exploration of TiO2 nanoparticle mediated microdynamic therapy on cancer treatment.

Radical therapy takes advantage of the reactive oxygen species produced in greater quantities within tumor cells than in normal cells. Here, for the first time, we explore a TiO2 nanoparticle mediated microwave induced radical therapy (termed as Microdynamic Therapy) as a new cancer treatment method. The experiments in vitro and in vivo demonstrate that colloidal TiO2 nanoparticles could significantly suppress the growth of osteosarcomas, even under low power (5 W) microwave (MW) irradiation for 5 min. The high photocatalytic activity of TiO2 nanoparticles efficiently utilizes the microwave-induced plasmonic effect for the formation of reactive oxygen species (ROS). Furthermore, TiO2 nanoparticles exhibit a higher cytotoxicity on cancer cells (osteosarcoma UMR-106 cells) than on normal cells (mouse fibroblast L929 cells). The effectiveness of TiO2 nanoparticles for microwave induced radical therapy demonstrates that this is a new landmark approach to treating cancers.

[Efficacy of one year treatment of icon infiltration resin on post-orthodontic white spots].

OBJECTIVE: To clinically evaluate the effectiveness of icon infiltration resin on masking post-orthodontic white spots. METHODS: Eight post-orthodontic patients with 6 maxillary anterior teeth showing signs of decalcification (total 48 teeth) were enrolled in this study. All teeth were treated with icon resin infiltration according to manufacturer's recommendation. Standardized digital photographs were taken before, immediately after and 1 week, 6 and 12 months after treatment. Before taking pictures the assigned teeth were cleaned using pumice and rubber polishing cups. The results were classified into three groups: completely masked, partially masked, and unchanged. Pictures of partially masked teeth were analyzed using image analysis software (Image-pro plus 6.0), size of the white spot lesion (W) and the whole tooth facial surface (T) were measured, then W/T ratio (in %) was calculated. The images were imported into image analysis software (Photoshop) which presented the images into histograms of gray scale from (0 to 255). RESULTS: Among the 48 teeth, 11 teeth (22.9%, 11/48) were classified as completely masked, whereas 37 teeth (77.1 %, 37/48) were classified as partially masked and no tooth unchanged. For partially masked teeth, W/T ratio decreased significantly after treatment from 31.37% to 7.99% (by Wilcoxon's signed rank test, P<0.05). The means at gray scale for the initial and 1 week photographs after treatment were 188.07± 5.62 and 143.20± 7.03 respectively, and there was significant difference by Wilcoxon,s signed rank test (P<0.05). The data of 6 and 12 months after treatment were 136.33± 4.54 and 139.57± 3.70 respectively, there were no significant differences (P>0.05) in comparison to 1 week after treatment. CONCLUSION: Resin infiltration was proven to be an effective treatment for masking white spot lesions. The surface color of infiltrated lesions remained stable after 12 months.

[Purification of total flavonoids from the extracts of Thesium Chinese with macroporous adsorption resin].

OBJECTIVE: To optimize the process parameters for purifying total flavonoids from Thesium chinese with D101 macroporous adsorption resin. METHODS: Purification technology of total flavonoids from the extracts of Thesium chinese was investigated by dynamic adsorption method with the transfer rates and the purity of total flavonoids as indexes. RESULTS: The optimal purifying conditions were as follows: sample concentration was 2.259 mg/mL with a speed of 1 BV/h, eluent concentration was 70% alcohol with a speed of 1BV/h. After purification, the transfer rate of total flavonoids was 94.44% and the purity of total flavonoids achieved 12.45%, which was 4 times of that by coarse extraction (2.91%). CONCLUSION: The purification technology is simple, stable and can significantly improve the contents of total flavoids in extracts.

Surface modification of titanium with antibacterial porous N-halamine coating to prevent peri-implant infection.

Peri-implant infection remains one of the greatest threats to orthopedics. The construction of bone implants with good antibacterial and osteogenic properties is beneficial for reducing the risk of implant-related infections and healing bone defects. In this study, N-halamine coating (namely N-Cl) was grafted onto alkali-heat treated titanium (Ti) using polydopamine to endow Ti-based orthopedic implants with strong bactericidal activity. Surface characterization revealed that the N-Cl coating has porous structure loaded with active chlorine (Cl+). The N-Cl coating also provided micro/nano-structured Ti surfaces with excellent antibacterial ability via transformation between N-H and N-Cl, and approximately 100% disinfection was achieved. Furthermore, the as-prepared N-Cl coating exhibited good biocompatibility and osteogenesis abilityin vitro. These results indicate that applying N-Cl coatings on Ti could prevent and treat peri-implant infections.

TAT&RGD Peptide-Modified Naringin-Loaded Lipid Nanoparticles Promote the Osteogenic Differentiation of Human Dental Pulp Stem Cells.

Background: Naringin is a naturally occurring flavanone that promotes osteogenesis. Owing to the high lipophilicity, poor in vivo bioavailability, and extensive metabolic alteration upon administration, the clinical efficacy of naringin is understudied. Additionally, information on the molecular mechanism by which it promotes osteogenesis is limited. Methods: In this study, we prepared TAT & RGD peptide-modified naringin-loaded nanoparticles (TAT-RGD-NAR-NPs), evaluated their potency on the osteogenic differentiation of human dental pulp stem cells (hDPSCs), and studied its mechanism of action through metabolomic analysis. Results: The particle size and zeta potential of TAT-RGD-NAR-NPs were 160.70±2.05 mm and -20.77±0.47mV, respectively. The result of cell uptake assay showed that TAT-RGD-NAR-NPs could effectively enter hDPSCs. TAT-RGD-NAR-NPs had a more significant effect on cell proliferation and osteogenic differentiation promotion. Furthermore, in metabolomic analysis, naringin particles showed a strong influence on the glycerophospholipid metabolism pathway of hDPSCs. Specifically, it upregulated the expression of PLA2G3 and PLA2G1B (two isozymes of phospholipase A2, PLA2), increased the biosynthesis of lysophosphatidic acid (LPA). Conclusion: These results suggested that TAT-RGD-NPs might be used for transporting naringin to hDPSCs for modulating stem cell osteogenic differentiation. The metabolomic analysis was used for the first time to elucidate the mechanism by which naringin promotes hDPSCs osteogenesis by upregulating PLA2G3 and PLA2G1B.

VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration via Enhancing Osteogenesis-Angiogenesis Coupling.

Background: Bone tissue defect, one of the common orthopaedicdiseases, is traumatizing and affects patient's lifestyle. Although autologous and xenograft bone transplantations are performed in bone tissue engineering, clinical development of bone transplantation is limited because ofvarious factors, such as varying degrees of immune rejection, lack of bone sources, and secondary damage to bone harvesting. Methods: We synthesised a heparinised gelatine-hydroxyapatite-tricalcium phosphate (HG-HA-TCP) scaffold loaded with sustained-release vascular endothelial growth factor (VEGF) analysed their structure, mechanical properties, and biocompatibility. Additionally, the effects of HG-HA-TCP (VEGF) scaffolds on osteogenic differentiation and vascularisation of stem cells from human exfoliated deciduous teeth (SHED) in vitro and bone regeneration in vivo were investigated. Results: HG-HA-TCP scaffold possessed good pore structure, mechanical properties, and biocompatibility. HG-HA-TCP scaffold loaded with VEGF could effectively promote SHED proliferation, migration, and adhesion. Moreover, HG-HA-TCP (VEGF) scaffold increased the expression of osteogenesis- and angiogenesis-related genes and promoted osteogenic differentiation and vascularisation in cells. In vivo results demonstrated that VEGF-loaded HG-HA-TCP scaffold improved new bone regeneration and enhanced bone mineral density, revealed byhistological, micro-CT and histochemical straining analyses. Osteogenic and angiogenic abilities of the three biological scaffolds wereranked as follows: HG-HA-TCP (VEGF) > G-HA-TCP (VEGF) > G-HA-TCP. Conclusion: HG-HA-TCP (VEGF) scaffold with good biocompatibility could create an encouraging osteogenic microenvironment that could accelerate vessel formation and osteogenesis, providing an effective scaffold for bone tissue engineering and developing new clinical treatment strategies for bone tissue defects.

Nitrogen-containing bisphosphonate-loaded micro-arc oxidation coating for biodegradable magnesium alloy pellets inhibits osteosarcoma through targeting of the mevalonate pathway.

Osteosarcoma (OS) remains one of the most threatening primary malignant human tumors of the bone, especially in the first or second decade of life. Unfortunately, the clinical therapeutic efficacy has not substantially improved over the past four decades. Therefore, to achieve efficient tumor eradication, a new approach to prevent tumor recurrence is urgently needed. Here, we develop a new bisphosphonate (BP)-loaded microarc oxidation (MAO) coated magnesium-strontium (Mg-Sr) alloy pellet that can inhibit OS, and we illuminate the cellular and molecular mechanisms of the inhibiting effect. To generate such pellets, nitrogen-containing BP is chemically conjugated with a MAO coating on hollow Mg-Sr alloys. We demonstrate that BP coated Mg pellet has multiple desired features for OS therapy through in vitro and in vivo studies. At the cellular level, BP coated Mg pellets not only induce apoptosis and necrosis, as well as antitumor invasion of OS cells in the two-dimensional (2D) cell culture environment, but also damage the formation of multicellular tumor spheroids by OS cell lines in the three-dimensional (3D) cell culture environment. At the in vivo level, BP coated Mg pellets can destroy tumors and prevent neoplasm recurrence via synergistic Mg degradation and drug release. It is further suggested that the superior inhibitory effect on OS of our pellet is achieved by inhibiting the mevalonate pathway at the molecular level. Hence, these results collectively show that the BP coated Mg pellet is a promising candidate for future applications in repairing defects after tumor removal in OS therapy.

Downregulation of ROR2 promotes dental pulp stem cell senescence by inhibiting STK4-FOXO1/SMS1 axis in sphingomyelin biosynthesis.

Dental pulp stem cells (DPSCs) play a vital role in tooth restoration, regeneration, and homeostasis. The link between DPSC senescence and tooth aging has been well-recognized. ROR2 plays an important role in aging-related gene expression. However, the expression and function of ROR2 in DPSC aging remain largely unknown. In this study, we found that ROR2 expression was significantly decreased in aged pulp tissues and DPSCs. The depletion of ROR2 in young DPSCs inhibits their self-renewal capacity, while its overexpression in aged DPSCs restores their self-renewal capacity. Interestingly, we found that sphingomyelin (SM) is involved in the senescence of DPSCs regulated by ROR2. Mechanistically, we confirmed that ROR2 inhibited the phosphorylation of STK4, which promoted the translocation of Forkhead Box O1 (FOXO1) to the nucleus. STK4 inhibition or knockdown of FOXO1 markedly increased the proliferation of DPSCs and upregulated the expression of SMS1, which catalyzed SM biogenesis. Moreover, FOXO1 directly bound to the SMS1 promoter, repressing its transcription. Our findings demonstrated the critical role of the ROR2/STK4-FOXO1/SMS1 axis in the regulation of SM biogenesis and DPSC senescence, providing a novel target for antagonizing tooth aging.

Comparative in vitro study on binary Mg-RE (Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu) alloy systems.

Correct selection of alloying elements is important for developing novel biodegradable magnesium alloys with superior mechanical and biological performances. In contrast to various reports on nutrient elements (Ca, Zn, Sr, etc.) as alloying elements of biomedical magnesium alloys, there is limited information about how to choose the right rare earth elements (REEs) as alloying elements of magnesium. In this work, 16 kinds of REEs were individually added into Mg, including Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Du, Ho, Er, Tm, Yb and Lu, to fabricate binary Mg-RE model alloys with different composition points. Under the same working history, comparative studies were undertaken and the impact of each kind of rare earth element on the microstructure, mechanical property, corrosion behavior and biocompatibility of Mg were investigated. The corresponding influence level for the 16 kinds of REEs were ranked. The results showed that the second phases were detected in some Mg-RE alloys, which were mainly composed of Mg12RE. By adding different REEs into Mg with proper contents, the mechanical properties of resulting Mg-RE binary alloys could be adjusted in wide range. The corrosion resistance of Mg-light REE alloys was generally better than Mg-heavy REE alloys. As for biocompatibility, Mg-RE model alloys showed no cytotoxic effect on MC3T3-E1 cells. The hemolysis rates of all experimental Mg-RE model alloys were lower than 5% except for Mg-Lu alloy model. In general, the addition of different REEs into Mg could improve its performance from different aspects. This work provides a better understanding on suitable REEs as alloying elements for magnesium, and the future R&D direction on biomedical Mg-RE alloys was proposed. STATEMENT OF SIGNIFICANCE: In contrast to various reports on nutrient elements (Ca, Zn, Sr, etc.) as alloying elements of biomedical magnesium alloys, until now there is limited information about how to choose the right rare earth elements (REEs) as alloying elements of magnesium. In this work, comparative studies were undertaken by individually adding 16 kinds of REEs, including Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Du, Ho, Er, Tm, Yb and Lu, into Mg to fabricate binary Mg-RE model alloys, with different composition points, then the impact of each kind of rare earth element on the microstructure, mechanical property, corrosion behavior and biocompatibility of Mg under the same working history were investigated, and the corresponding influence level for the 16 kinds of REEs were ranked. This work provides a better understanding on suitable REEs as alloying elements for magnesium, and the future R&D direction on biomedical Mg-RE alloys was proposed.

In vitro and in vivo studies of Mg-30Sc alloys with different phase structure for potential usage within bone.

Proper alloying magnesium with element scandium (Sc) could transform its microstructure from α phase with hexagonal closed-packed (hcp) structure into ß phase with body-cubic centered (bcc) structure. In the present work, the Mg-30 wt% Sc alloy with single α phase, dual phases (α + ß) or ß phase microstructure were developed by altering the heat-treatment routines and their suitability for usage within bone was comprehensively investigated. The ß phased Mg-30 wt% Sc alloy showed the best mechanical performance with ultimate compressive strength of 603 ±â€¯39 MPa and compressive strain of 31 ±â€¯3%. In vitro degradation test showed that element scandium could effectively incorporate into the surface corrosion product layer, form a double-layered structure, and further protect the alloy matrix. No cytotoxic effect was observed for both single α phased and ß phased Mg-30 wt% Sc alloys on MC3T3 cell line. Moreover, the ß phased Mg-30 wt%Sc alloy displayed acceptable corrosion resistance in vivo (0.06 mm y-1) and maintained mechanical integrity up to 24 weeks. The degradation process did not significantly influence the hematology indexes of inflammation, hepatic or renal functions. The bone-implant contact ratio of 75 ±â€¯10% after 24 weeks implied satisfactory integration between ß phased Mg-30 wt%Sc alloy and the surrounding bone. These findings indicate a potential usage of the bcc-structured Mg-Sc alloy within bone and might provide a new strategy for future biomedical magnesium alloy design. STATEMENT OF SIGNIFICANCE: Scandium is the only rare earth element that can transform the matrix of magnesium alloy into bcc structure, and Mg-30 wt%Sc alloy had been recently reported to exhibit shape memory effect. The aim of the present work is to study the feasibility of Mg-30 wt%Sc alloy with different constitutional phases (single α phase, single ß phase or dual phases (α + ß)) as biodegradable orthopedic implant by in vitro and in vivo testings. Our findings showed that ß phased Mg-30 wt%Sc alloy which is of bcc structure exhibited improved strength and superior in vivo degradation performance (0.06 mm y-1). No cytotoxicity and systematic toxicity were shown for ß phased Mg-30 wt%Sc alloy on MC3T3 cell model and rat organisms. Moreover, good osseointegration, limited hydrogen gas release and maintained mechanical integrity were observed after 24 weeks' implantation into the rat femur bone.

Improving antitumor outcomes for palliative intratumoral injection therapy through lecithin- chitosan nanoparticles loading paclitaxel- cholesterol complex.

BACKGROUND: Intratumoral injection is a palliative treatment that aims at further improvement in the survival and quality of life of patients with advanced or recurrent carcinomas, or cancer patients with severe comorbidities or those with a poor performance status. METHODS: In this study, a solvent-injection method was used to prepare paclitaxel-cholesterol complex-loaded lecithin-chitosan nanoparticles (PTX-CH-loaded LCS_NPs) for intratumoral injection therapy, and the physicochemical properties of NPs were well characterized. RESULTS: The particle size and zeta potential of PTX-CH-loaded LCS_NPs were 142.83±0.25 nm and 13.50±0.20 mV, respectively. Release behavior of PTX from PTX-CH-loaded LCS_NPs showed a pH-sensitive pattern. The result of cell uptake assay showed that PTX-CH-loaded LCS_NPs could effectively enter cells via the energy-dependent caveolae-mediated endocytosis and macropinocytosis in company with the Golgi apparatus. Meanwhile, PTX-CH-loaded LCS_NPs had a better ability to induce cell apoptosis than PTX solution. The in vivo antitumor results suggested that PTX-CH-loaded LCS_NPs effectively inhibited mouse mammary cancer growth and metastasis to distant organs and significantly improved the survival rate of tumor-bearing mice by intratumoral administration. CONCLUSION: In general, our study demonstrated that PTX-CH-loaded LCS_NPs used for palliative treatment by intratumoral injection showed improved safety and antitumor efficacy, which provided an alternative approach in the field of palliative chemotherapy.

On the Structure and Transdermal Profile of Liquid Crystals Based on Phytantriol.

BACKGROUND: There has been a growing concern in transdermal drug technology over the past several decades. As a novel transdermal delivery system, Lyotropic liquid crystals (LLC) still face challenges such as drug loading, limited drug permeation and instability of systems. LLC system is so sensitive that a very subtle change in composition may induce a phase transformation or conversion of spatial configuration, and result in a diverse percutaneous delivery subsequently. OBJECTIVE: To find out the effects of hydrophilic and lipophilic components on the structure and transdermal properties of LLCs, hydrophilic sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) was chosen as a model drug and a skin permeation enhancer, respectively, several formulations were prepared and compared. METHOD: The structure of LLC was evaluated by visual observation, Cross-polarizing light microscopy (CPLM) and Small angle X-ray diffraction (SAXS). The Franz diffusion cell was applied to investigate its skin penetration of SH across the rat skins. Fourier transform infrared spectroscopy (FTIR) was recorded to evaluate the intermolecular interaction between the LC samples and stratum corneum (SC). CONCLUSION: The results showed that a controlled transdermal process might be obtained by adjusting the ratios of different drugs or loading doses when LLCs with dual-components were applied.

In Vitro and in Vivo Studies on Biomedical Magnesium Low-Alloying with Elements Gadolinium and Zinc for Orthopedic Implant Applications.

Ternary magnesium alloys with low combined addition of elements gadolinium and zinc were developed in the present work, with their microstructures, mechanical properties, in vitro degradation behaviors, and cytotoxicity being systematically studied. Furthermore, the Mg-1.8Zn-0.2Gd alloy, with the best in vitro performance, was implanted into Sprague Dawley rats to examine its in vivo degradation performance for up to 6 months. It was found that Mg-1.8Zn-0.2Gd, composed of a single α-Mg phase, owned excellent strength and toughness that were comparable to the CE marked MAGNEZIX, the mischmetal added Mg alloy. Owing to the uniform single-phased microstructure, the degradation rate of this alloy was around 0.12 mm/y measured by electrochemical testing, which was comparable to high purity magnesium. Moreover, the Mg-1.8Zn-0.2Gd alloy exhibited no cytotoxicity to L929, MG63, and VSMC cells. In vivo degradation characterized by micro-computed tomography revealed that the Mg-1.8Zn-0.2Gd implant could maintain structural integrity in the first 2 months, and serious degradation could be observed after 6 months. A remarkable 100% survival rate of experimental animals was observed with no negative effects on bone tissues. The implant and the surrounding bone were well integrated within 2 months, implying good biocompatibility and osteoconductivity of the experimental alloy. On the basis of the above findings, the feasibility of Mg-Zn-Gd alloys for use as orthopedic implants was systematically discussed. This study provides a new strategy for development of high-performance Mg-rare earth (RE)-based alloys with superior mechanical properties and corrosion resistance while effectively avoiding the possible standing toxic effect of RE elements.

Rare Gingival Metastasis by Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) uncommonly metastasizes to the gingiva, which always means a poor outcome. We reported a rare HCC case with multiple metastases to gingiva, lungs, and brain. A 60-year-old man was initially diagnosed as HCC with metastases to double lungs. He was subjected to a transarterial chemoembolization (TACE) (5-fluorouracil, 750 mg) and two cycles of intravenous chemotherapy (gemcitabine 1.8 g at days 1 and 8, oxaliplatin 200 mg at day 2, every 4 weeks). However, the volume of liver tumor still increased. A bean-size gingival nodule growing with occasional bleeding was also found. TACE (5-fluorouracil 750 mg, perarubicin 40 mg, cisplatin 20 mg) was performed again and an oral sorafenib therapy (400 mg, twice per day) was adopted. The disease maintained relatively stable for about 6 months until a second obvious progress. The gingival nodule was then palliatively excised and identified as a poorly differentiated metastatic HCC by histopathological examination. Best supportive treatments were made since the performance score was too bad. Finally, cerebral metastases occurred and the patient died of systemic failure. Upon review of previous reports, we discussed risk factors, clinical and pathological characteristics, treatments, and prognosis of gingival metastasis by HCC.

Development of magnesium-based biodegradable metals with dietary trace element germanium as orthopaedic implant applications.

From the perspective of element biosafety and dietetics, the ideal alloying elements for magnesium should be those which are essential to or naturally presented in human body. Element germanium is a unique metalloid in the carbon group, chemically similar to its group neighbors, Si and Sn. It is a dietary trace element that naturally presents in human body. Physiological role of Ge is still unanswered, but it might be necessary to ensure normal functioning of the body. In present study, novel magnesium alloys with dietary trace element Ge were developed. Feasibility of those alloys to be used as orthopaedic implant applications was systematically evaluated. Mg-Ge alloys consisted of α-Mg matrix and eutectic phases (α-Mg + Mg2Ge). Mechanical properties of Mg-Ge alloys were comparable to current Mg-Ca, Mg-Zn and Mg-Sr biodegradable metals. As-rolled Mg-3Ge alloy exhibited outstanding corrosion resistance in vitro (0.02 mm/y, electrochemical) with decent corrosion rate in vivo (0.6 mm/y, in rabbit tibia). New bone could directly lay down onto the implant and grew along its surface. After 3 months, bone and implant were closely integrated, indicating well osseointegration being obtained. Generally, this is a pioneering study on the in vitro and in vivo performances of novel Mg-Ge based biodegradable metals, and will benefit the future development of this alloy system. STATEMENT OF SIGNIFICANCE: The ideal alloying elements for magnesium-based biodegradable metals should be those which are essential to or naturally presented in human body. Element germanium is a unique metalloid in the carbon group. It is a dietary trace element that naturally presents in human body. In present study, feasibility of Mg-Ge alloys to be utilized as orthopedic applications was systematically investigated, mainly focusing on the microstructure, mechanical property, corrosion behavior and biocompatibility. Our findings showed that Mg-3Ge alloy exhibited superior corrosion resistance to current Mg-Ca, Mg-Zn and Mg-Sr alloys with favorable biocompatibility. This is a pioneering study on the in vitro &in vivo performances of Mg-Ge biodegradable metals, and will benefit the future development of this alloy system.

Toward a Molecular Understanding of the Antibacterial Mechanism of Copper-Bearing Titanium Alloys against Staphylococcus aureus.

The antibacterial mechanism of the Cu-containing materials has not been fully understood although such understanding is crucial for the sustained clinical use of Cu-containing antibacterial materials such as bone implants. The aim of this study is to investigate the molecular mechanisms by which the Gram-positive Staphylococcus aureus is inactivated through Cu-bearing titanium alloys (Ti6Al4V5Cu). Cu ions released from the alloys are found to contribute to lethal damage of bacteria. They destroy the permeability of the bacterial membranes, resulting in the leakage of reducing sugars and proteins from the cells. They also promote the generation of bacteria-killing reactive oxygen species (ROS). The ROS production is confirmed by several assays including fluorescent staining of intracellular oxidative stress, detection of respiratory chain activity, and measurement of the levels of lipid peroxidation, catalase, and glutathione. Furthermore, the released Cu ions show obvious genetic toxicity by interfering the replication of nuc (species-specific) and 16SrRNA genes, but with no effect on the genome integrity. All of these effects lead to the antibacterial effect of Ti6Al4V5Cu. Collectively, our work reconciles the conflicting antibacterial mechanisms of Cu-bearing metallic materials or nanoparticles reported in the literature and highlights the potential use of Ti6Al4V5Cu alloys in inhibiting bacterial infections.

The synergistic antibacterial activity and mechanism of multicomponent metal ions-containing aqueous solutions against Staphylococcus aureus.

Silver (Ag+), zinc (Zn2+) and copper (Cu2+) ions, are well known for their broad-spectrum antibacterial activities while generating low resistance. However, whether or multiple metal ions in aqueous solutions acted synergistically or antagonistically antimicrobial properties, remained unknown. Therefore, it was of great significance to investigate the antibacterial properties of multicomponent metal ions-containing aqueous solutions. In this study, the antibacterial activities of multicomponent metal ions-containing aqueous solutions were investigated for the first time. We found that the antibacterial activities of multicomponent metal ions-containing aqueous solutions were higher than those of single metal ion-containing aqueous solution. Furthermore, the synergistic antibacterial mechanism of these multicomponent metal ions-containing aqueous solutions was first investigated. The generation of reactive oxygen species (ROS) through electron transfer in the enzymes and Fenton reactions formed the main synergistic antibacterial mechanism of the multicomponent metal ions-containing aqueous solutions. Therefore, the encouraging results demonstrate the great potential applications of multicomponent metal ions for the design of new biomaterials or prosthesis containing Ag-Cu-Zn alloy which can release Ag+, Zn2+ and Cu2+ and minimize the risk of hospital acquired infection.

Probing the adjustments of macromolecules during their surface adsorption.

Thiol-terminated polymers poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC-SH), poly(N,N-isopropylacrylamide) (PNIPAM-SH), and poly(tert-butyl acrylate) (PtBA-SH) were synthesized, and the polymers were grafted on the gold surfaces of quartz crystal microbalance with dissipation (QCM-D) and surface plasmon resonance (SPR) sensor chips to form brushes. The grafting process of the polymer brushes as well as protein adsorption onto the brush layers was monitored by in situ QCM-D and SPR techniques. By examining the changes in frequency and dissipation factor as well as the value of ∂D/∂f from QCM-D measurements, different stages of the polymer grafting and protein adsorption are distinguished. The most interesting discovery is the conformation change of BSA protein adsorption from a weakly adsorbed native state to a strongly immobilized denatured state on the polymer brushes. The corresponding change in BSA adsorption from a reversible state to an irreversible state was confirmed by SPR measurements. The adsorption of protein on the polymer brushes' surface relies largely on interaction between the protein and the polymers, and the stronger hydrophilicity of the surfaces is proved to be more effective to suppress the protein adsorption. Analysis of the D-f plot of QCM-D measurements helps to characterize different binding strength of protein and the underlying polymer surface.