NFAT5 mediates hypertonic stress-induced atherosclerosis via activating NLRP3 inflammasome in endothelium.

BACKGROUND: How high-salt intake leads to the occurrence of many cardiovascular diseases such as atherosclerosis is a fundamental question in pathology. Here we postulated that high-salt-induced NFAT5 controls the inflammasome activation by directly regulating NLRP3, which mediates the expression of inflammatory- and adhesion-related genes in vascular endothelium, resulting in the formation of atherosclerosis. METHODS: Atherosclerosis-prone apolipoprotein E-deficient (ApoE-/-) mice which accumulate cholesterol ester-enriched particles in the blood due to poor lipoprotein clearance capacity were used as the atherosclerosis model in vivo. Cultured endothelial cells (ECs) and monocytes under high-salt condition were used to explore the atheroprone role of the activation of NFAT5-NLRP3 inflammasome in vascular endothelium in vitro. Bioinformatic analysis and chromatin immunoprecipitation assay were used to identify the DNA binding sites of NFAT5 on promoters of NLRP3 and IL-1ß. RESULTS: We first observe that high-salt intake promotes atherosclerosis formation in the aortas of ApoE-/- mice, through inducing the expression of NFAT5, NLRP3, and IL-1ß in endothelium. Overexpression of NFAT5 activates NLRP3-inflammasome and increases the secretion of IL-1ß in ECs partly via ROS. Chromatin immunoprecipitation assay demonstrates that NFAT5 directly binds to the promoter regions of NLRP3 and IL-1ß in endothelial cells subjected to the high-salt environment. CONCLUSIONS: Our study identifies NFAT5 as a new and essential transcription factor that is required for the early activation of NLRP3-inflammasome-mediated endothelium innate immunity, contributing to the formation of atherosclerosis under hypertonic stress induction.

Recyclable heparin and chitosan conjugated magnetic nanocomposites for selective removal of low-density lipoprotein from plasma.

A new fabrication protocol is described to obtain heparin and chitosan conjugated magnetic nanocomposite as a blood purification material for removal of low-density lipoprotein (LDL) from blood plasma. The adsorbent could be easily separated with an external magnet for recyclable use since it had a magnetic core. The LDL level of plasma decreased by 67.3 % after hemoperfusion for 2 h. Moreover, the adsorbent could be recycled simply washing with NaCl solution. After eight cycles, the removal efficiency of the adsorbent was still above 50 %. The recyclable magnetic adsorbent had good blood compatibility due to the conjugation of heparin to the chitosan-coated magnetic nanocomposites. The fabricated magnetic adsorbent could be applied for LDL apheresis without side effects.

Enhanced vascularization and osseointegration under osteoporotic conditions through functional peptide coating on implant surfaces.

Patients with osteoporosis face challenges such as decreased bone density, a sparse trabecular structure, weakened osteogenic ability, and impaired angiogenesis, leading to poor osseointegration and implant failure. Surface modification of implants with biologically active molecules possessing various functions is an effective strategy to improve osseointegration. In this study, we constructed a simple multifunctional coating interface that significantly improves osseointegration. In brief, a multifunctional coating interface was constructed by coupling the Rgd adhesive peptide, Ogp osteogenic peptide, and Ang angiogenic peptide to Lys6 (k6), which self-assembled layer by layer with TA to form the (TA-Rgd@ogp@ang)n composite membrane. This study characterized the surface morphology and biomechanical properties of the coating under both gas and liquid phases and monitored the deposition process and reaction rate of the two peptides with TA using a quartz crystal microbalance. Moreover, (TA-Rgd@ogp@ang)n exhibited a triple synergistic effect on cell migration and adhesion, osteogenic differentiation, and angiogenesis. It also ameliorated the high ROS environment characteristic of osteoporosis pathology, promoted angiogenic bone defect regeneration in osteoporosis, thereby avoiding poor osseointegration. This work provides a new approach for the prevention of implant failure in pathological environments by constructing multifunctional coatings on implants, with tremendous potential applications in the fields of orthopedics and dentistry.

H2S-Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation.

Abnormal activation of the intestinal mucosal immune system, resulting from damage to the intestinal mucosal barrier and extensive invasion by pathogens, contributes to the pathogenesis of inflammatory bowel disease (IBD). Current first-line treatments for IBD have limited efficacy and significant side effects. An innovative H2S-releasing montmorillonite nanoformulation (DPs@MMT) capable of remodeling intestinal mucosal immune homeostasis, repairing the mucosal barrier, and modulating gut microbiota is developed by electrostatically adsorbing diallyl trisulfide-loaded peptide dendrimer nanogels (DATS@PDNs, abbreviated as DPs) onto the montmorillonite (MMT) surface. Upon rectal administration, DPs@MMT specifically binds to and covers the damaged mucosa, promoting the accumulation and subsequent internalization of DPs by activated immune cells in the IBD site. DPs release H2S intracellularly in response to glutathione, initiating multiple therapeutic effects. In vitro and in vivo studies have shown that DPs@MMT effectively alleviates colitis by eliminating reactive oxygen species (ROS), inhibiting inflammation, repairing the mucosal barrier, and eradicating pathogens. RNA sequencing revealed that DPs@MMT exerts significant immunoregulatory and mucosal barrier repair effects, by activating pathways such as Nrf2/HO-1, PI3K-AKT, and RAS/MAPK/AP-1, and inhibiting the p38/ERK MAPK, p65 NF-κB, and JAK-STAT3 pathways, as well as glycolysis. 16S rRNA sequencing demonstrated that DPs@MMT remodels the gut microbiota by eliminating pathogens and increasing probiotics. This study develops a promising nanoformulation for IBD management.

A biodegradable Zn-5Gd alloy with biomechanical compatibility, cytocompatibility, antibacterial ability, and in vitro and in vivo osteogenesis for orthopedic applications.

Zinc (Zn) and some of its alloys are recognized as promising biodegradable implant materials due to their acceptable biocompatibility, facile processability, and moderate degradation rate. Nevertheless, the limited mechanical properties and stability of as-cast Zn alloys hinder their clinical application. In this work, hot-rolled (HR) and hot-extruded (HE) Zn-5 wt.% gadolinium (Zn-5Gd) samples were prepared by casting and respectively combining with hot rolling and hot extrusion for bone-implant applications. Their microstructure evolution, mechanical properties, corrosion behavior, cytotoxicity, antibacterial ability, and in vitro and in vivo osteogenesis were systematically evaluated. The HR and HE Zn-5Gd exhibited significantly improved mechanical properties compared with those of their pure Zn counterparts and the HR Zn-5Gd showed a unique combination of tensile properties with an ultimate tensile strength of ∼311.6 MPa, yield strength of ∼236.5 MPa, and elongation of ∼40.6%, all of which are greater than the mechanical properties required for bone-implant materials. The HR and HE Zn-5Gd showed higher corrosion resistance than their pure Zn counterpart in Hanks' solution and the HE Zn-5Gd had the lowest corrosion rate of 155 µm/y measured by electrochemical corrosion and degradation rate of 26.9 µm/y measured by immersion testing. The HR and HE Zn-5Gd showed high cytocompatibility toward MC3T3-E1 and MG-63 cells, high antibacterial effects against S. aureus, and better in vitro osteogenic activity than their pure Zn counterparts. Furthermore, the HE Zn-5Gd exhibited better in vivo biocompatibility, osteogenesis, and osteointegration ability than pure Zn and pure Ti. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, corrosion behaviors, cytocompatibility, antibacterial ability, in vitro and in vivo osteogenesis of biodegradable Zn-Gd alloy for bone-implant applications. Our findings demonstrate that the hot-rolled (HR) Zn-5Gd showed a unique combination of tensile properties with an ultimate tensile strength of ∼311.6 MPa, yield strength of ∼236.5 MPa, and elongation of ∼40.6%. The HR and HE Zn-5Gd showed higher corrosion resistance than their pure Zn counterpart in Hanks' solution. The HR and HE Zn-5Gd showed high cytocompatibility toward MC3T3-E1 and MG-63 cells, good antibacterial effects against S. aureus, and better in vitro osteogenic activity. Furthermore, the HE Zn-5Gd exhibited better in vivo biocompatibility, osteogenesis, and osteointegration ability than pure Zn and pure Ti.

Mechanical properties, corrosion behavior, and in vitro and in vivo biocompatibility of hot-extruded Zn-5RE (RE = Y, Ho, and Er) alloys for biodegradable bone-fixation applications.

Biodegradable Zn alloys have significant application potential for hard-tissue implantation devices owing to their suitable degradation behavior and favorable biocompatibility. Nonetheless, pure Zn and its alloys in the as-cast state are mechanically instable and low in strength, which restricts their clinical applicability. Here, we report the exceptional mechanical, corrosion, and biocompatibility properties of hot-extruded Zn-5RE (wt.%, RE = rare earth of Y; or Ho; or Er) alloys intended for use in biodegradable bone substitutes. The microstructural characteristics, mechanical behavior, corrosion resistance, cytocompatibility, osteogenic differentiation, and capacity of osteogenesis in vivo of the Zn-5RE alloys are comparatively investigated. The Zn-5Y alloy demonstrates the best tensile properties, encompassing a 138 MPa tensile yield strength, a 302 MPa ultimate tensile strength, and 63% elongation, while the Zn-5Ho alloy shows the highest compression yield strength of 260 MPa and Vickers hardness of 104 HV. The Zn-5Er alloy shows a 126 MPa tensile yield strength, a 279 MPa ultimate tensile strength, 52% elongation, a 196 MPa compression yield strength, and a 101 HV Vickers microhardness. Further, the Zn-5Er alloy has a 130 µm per year corrosion rate in electrochemical tests and a 26 µm per year degradation rate in immersion tests, which is the lowest among the tested alloys. It also has the best in vitro osteogenic differentiation ability and capacity for osteogenesis and osteointegration in vivo after implantation in rat femurs among the Zn-5RE alloys, indicating promising potential in load-bearing biodegradable internal bone-fixation applications. STATEMENT OF SIGNIFICANCE: This work reports the exceptional mechanical, corrosion, and biocompatibility properties of hot-extruded (HE) Zn-5 wt.%-rare earth (Zn-5RE) alloys using single yttrium (Y), holmium (Ho), and erbium (Er) alloying for biodegradable bone-implant applications. Our findings demonstrate that the HE Zn-5Er alloy showed σuts of 279 MPa, tensile yield strength of 126 MPa, elongation of 51.6%, compression yield strength of 196 MPa, and microhardness of 101.2 HV. Further, HE Zn-5Er showed the lowest electrochemical corrosion rate of 130 µm/y and lowest degradation rate of 26 µm/y, and the highest in vitro osteogenic differentiation ability, in vivo osteogenesis, and osteointegration ability after implantation in rat femurs among the Zn-5RE alloys, indicating promising potential in load-bearing biodegradable internal bone-fixation applications.

Enhanced Mechanical Properties, Corrosion Resistance, Cytocompatibility, Osteogenesis, and Antibacterial Performance of Biodegradable Mg-2Zn-0.5Ca-0.5Sr/Zr Alloys for Bone-Implant Application.

Magnesium (Mg) alloys are widely used in bone fixation and bone repair as biodegradable bone-implant materials. However, their clinical application is limited due to their fast corrosion rate and poor mechanical stability. Here, the development of Mg-2Zn-0.5Ca-0.5Sr (MZCS) and Mg-2Zn-0.5Ca-0.5Zr (MZCZ) alloys with improved mechanical properties, corrosion resistance, cytocompatibility, osteogenesis performance, and antibacterial capability is reported. The hot-extruded (HE) MZCZ sample exhibits the highest ultimate tensile strength of 255.8 ± 2.4 MPa and the highest yield strength of 208.4 ± 2.8 MPa and an elongation of 15.7 ± 0.5%. The HE MZCS sample shows the highest corrosion resistance, with the lowest corrosion current density of 0.2 ± 0.1 µA cm-2 and the lowest corrosion rate of 4 ± 2 µm per year obtained from electrochemical testing, and a degradation rate of 368 µm per year and hydrogen evolution rate of 0.83 ± 0.03 mL cm-2 per day obtained from immersion testing. The MZCZ sample shows the highest cell viability in relation to MC3T3-E1 cells among all alloy extracts, indicating good cytocompatibility except at 25% concentration. Furthermore, the MZCZ alloy shows good antibacterial capability against Staphylococcus aureus.

Near-Infrared Responsive Biomimetic Titanate/TiO2-X Heterostructure: A Therapeutic Strategy for Combating Implant-Associated Infection and Enhancing Osseointegration.

Implant-associated infections and delayed osseointegration are major challenges for the clinical success of titanium implants. To enhance antibacterial effects and promote early osseointegration, we developed a synergistic photothermal (PTT)/photodynamic (PDT) therapy strategy based on near-infrared (NIR) responsive biomimetic micro/nano titanate/TiO2-X heterostructure coatings (KMNW and NaMNS) in situ constructed on the surface of titanium implants. Specifically, KMNW and NaMNS significantly enhanced photothermal conversion capabilities, achieving localized high temperatures of 48-51 °C and promoting substantial amounts of reactive oxygen species production under 808 nm irradiation. In vitro antibacterial experiments demonstrated that KMNW achieved the highest antibacterial rates against Staphylococcus aureus and Escherichia coli, at 98.78 and 98.33% respectively. Moreover, by mimicking the three-dimensional fibrous network of the extracellular matrix during bone healing, both KMNW and NaMNS markedly promoted the proliferation and osteogenic differentiation of osteoblasts. In vivo implantation studies further confirmed these findings, with KMNW and NaMNS exhibiting superior antibacterial performance under NIR irradiation─94.45% for KMNW and 92.66% for NaMNS. Moreover, KMNW and NaMNS also significantly promoted new bone formation and improved osseointegration in vivo. This study presents a promising PTT/PDT therapeutic strategy for dentistry and orthopedics by employing NIR-responsive biomimetic coatings to combat implant-associated infection and accelerate osseointegration.

Ferroptosis Nanomedicine: Clinical Challenges and Opportunities for Modulating Tumor Metabolic and Immunological Landscape.

Ferroptosis, a type of regulated cell death driven by iron-dependent phospholipid peroxidation, has captured much attention in the field of nanomedicine since it was coined in 2012. Compared with other regulated cell death modes such as apoptosis and pyroptosis, ferroptosis has many distinct features in the molecular mechanisms and cellular morphology, representing a promising strategy for treating cancers that are resistant to conventional therapeutic modalities. Moreover, recent insights collectively reveal that ferroptosis is tightly connected to the maintenance of the tumor immune microenvironment (TIME), suggesting the potential application of ferroptosis therapies for evoking robust antitumor immunity. From a biochemical perspective, ferroptosis is intricately regulated by multiple cellular metabolic pathways, including iron metabolism, lipid metabolism, redox metabolism, etc., highlighting the importance to elucidate the relationship between tumor metabolism and ferroptosis for developing antitumor therapies. In this review, we provide a comprehensive discussion on the current understanding of ferroptosis-inducing mechanisms and thoroughly discuss the relationship between ferroptosis and various metabolic traits of tumors, which offer promising opportunities for direct tumor inhibition through a nanointegrated approach. Extending from the complex impact of ferroptosis on TIME, we also discussed those important considerations in the development of ferroptosis-based immunotherapy, highlighting the challenges and strategies to enhance the ferroptosis-enabled immunostimulatory effects while avoiding potential side effects. We envision that the insights in this study may facilitate the development and translation of ferroptosis-based nanomedicines for tumor treatment.

Functionally Tailored Metal-Organic Framework Coatings for Mediating Ti Implant Osseointegration.

Owing to their mechanical resilience and non-toxicity, titanium implants are widely applied as the major treatment modality for the clinical intervention against bone fractures. However, the intrinsic bioinertness of Ti and its alloys often impedes the effective osseointegration of the implants, leading to severe adverse complications including implant loosening, detachment, and secondary bone damage. Consequently, new Ti implant engineering strategies are urgently needed to improve their osseointegration after implantation. Remarkably, metalorganic frameworks (MOFs) are a class of novel synthetic material consisting of coordinated metal species and organic ligands, which have demonstrated a plethora of favorable properties for modulating the interfacial properties of Ti implants. This review comprehensively summarizes the recent progress in the development of MOF-coated Ti implants and highlights their potential utility for modulating the bio-implant interface to improve implant osseointegration, of which the discussions are outlined according to their physical traits, chemical composition, and drug delivery capacity. A perspective is also provided in this review regarding the current limitations and future opportunities of MOF-coated Ti implants for orthopedic applications. The insights in this review may facilitate the rational design of more advanced Ti implants with enhanced therapeutic performance and safety.

Construction of multifunctional coating with cationic amino acid-coupled peptides for osseointegration of implants.

Osseointegration is an important indicator of implant success. This process can be improved by coating modified bioactive molecules with multiple functions on the surface of implants. Herein, a simple multifunctional coating that could effectively improve osseointegration was prepared through layer-by-layer self-assembly of cationic amino acids and tannic acid (TA), a negatively charged molecule. Osteogenic growth peptide (OGP) and the arginine-glycine-aspartic acid (RGD) functional polypeptides were coupled with Lys6 (K6), the two polypeptides then self-assembled with TA layer by layer to form a composite film, (TA-OGP@RGD)n. The surface morphology and biomechanical properties of the coating were analyzed in gas and liquid phases, and the deposition process and kinetics of the two peptides onto TA were monitored using a quartz crystal microbalance. In addition, the feeding consistency and adsorption ratios of the two peptides were explored by using fluorescence visualization and quantification. The (TA-OGP@RGD)n composite membrane mediated the early migration and adhesion of cells and significantly promoted osteogenic differentiation and mineralization of the extracellular matrix in vitro. Additionally, the bifunctional peptide exhibited excellent osteogenesis and osseointegration owing to the synergistic effect of the OGP and RGD peptides in vivo. Simultaneously, the (TA-OGP@RGD)n membrane regulated the balance of reactive oxygen species in the cell growth environment, thereby influencing the complex biological process of osseointegration. Thus, the results of this study provide a novel perspective for constructing multifunctional coatings for implants and has considerable application potential in orthopedics and dentistry.

Preparation of co-electrospinning membrane loaded with simvastatin and substance P to accelerate bone regeneration by promoting cell homing, angiogenesis and osteogenesis.

Bone regeneration is a complex process that requires the coordination of various biological events. Developing a tissue regeneration membrane that can regulate this cascade of events is challenging. In this study, we aimed to fabricate a membrane that can enrich the damaged area with mesenchymal stem cells, improve angiogenesis, and continuously induce osteogenesis. Our approach involved creating a hierarchical polycaprolactone/gelatin (PCL/GEL) co-electrospinning membrane that incorporated substance P (SP)-loaded GEL fibers and simvastatin (SIM)-loaded PCL fibers. The membrane could initiate a burst release of SP and a slow/sustained release of SIM for over a month. In vitro experiments, including those related to angiogenesis and osteogenesis (e.g., migration, endothelial network formation, alkaline phosphatase activity, mineralization, and gene expression), clearly demonstrated the membrane's superior ability to improve cell homing, revascularization, and osteogenic differentiation. Furthermore, a series of in vivo studies, including immunofluorescence of CD29+/CD90+ double-positive cells and immunohistochemical staining for CD34 and vWF, confirmed the co-electrospinning membrane's ability to enhance MSC migration and revascularization response after five days of implantation. After one month, the Micro-CT and histological (Masson and H&E) results showed accelerated bone regeneration. Our findings suggest that a co-electrospinning membrane with time-tunable drug delivery could advance the development of tissue engineering therapeutic strategies and potentially improve patient outcomes.

Study on the Local Anti-Osteoporosis Effect of Polaprezinc-Loaded Antioxidant Electrospun Membrane.

BACKGROUND: Compared with the healthy condition, osteoporotic bone defects are often accompanied by poor osteogenesis and excessive reactive oxygen species (ROS), which pose serious challenges to bone augmentation and repair by normal resorbable guided bone regeneration (GBR) membrane. PURPOSE: Polaprezinc (PZ) was loaded into polycaprolactone/gelatin (PG) hybrid electrospun nanofibers to fabricate a GBR membrane with antioxidant and osteogenesis ability. METHODS: A series of physicochemical characterization were performed by scanning electron microscopy, Fourier-transform infrared spectroscopy, and water contact angle measurement. In addition to membrane degradation and PZ release detection, membranes were tested for cell viability, differentiation, and protein expression in MC3T3-E1 cells by CCK8, alkaline phosphatase activity, mineralization, and Western blotting assays. The membrane osteogenic capacity in cranial bone defects was studied by micro-CT in vivo. RESULTS: PZ was successfully doped into the PCL/GEL nanofibers to form a hydrophilic GBR membrane. The cumulative release of PZ was closely related to the membrane degradation behavior. PG/0.4%PZ membranes produced the best protective effect on cell proliferation/differentiation under oxidative stress microenvironment; however, the PG/0.8%PZ membrane was cytotoxic. Western blotting demonstrated that the PZ-loaded membrane upregulated the Nrf2/HO-1/SOD1 signaling molecules in a concentration-dependent manner. In addition, micro-CT results showed an abundant formation of new bones in the PG/0.4%PZ group compared to the PG group. CONCLUSION: PZ-loaded degradable PG membranes (especially PG/0.4%PZ) have great potential to accelerate bone regeneration in oxidative stress-related diseases.

Improvement in osteogenesis, vascularization, and corrosion resistance of titanium with silicon-nitride doped micro-arc oxidation coatings.

Titanium (Ti) implants have been widely used for the treatment of tooth loss due to their excellent biocompatibility and mechanical properties. However, modifying the biological properties of these implants to increase osteointegration remains a research challenge. Additionally, the continuous release of various metal ions in the oral microenvironment due to fluid corrosion can also lead to implant failure. Therefore, simultaneously improving the bioactivity and corrosion resistance of Ti-based materials is an urgent need. In recent decades, micro-arc oxidation (MAO) has been proposed as a surface modification technology to form a surface protective oxide layer and improve the comprehensive properties of Ti. The present study doped nano silicon nitride (Si3N4) particles into the Ti surface by MAO treatment to improve its corrosion resistance and provide excellent osteoinduction by enhancing alkaline phosphatase activity and osteogenic-related gene expression. In addition, due to the presence of silicon, the Si3N4-doped materials showed excellent angiogenesis properties, including the promotion of cell migration and tubule formation, which play essential roles in early recovery after implantation.

High proportion strontium-doped micro-arc oxidation coatings enhance early osseointegration of titanium in osteoporosis by anti-oxidative stress pathway.

The excessive accumulation of reactive oxygen species (ROS) under osteoporosis precipitates a microenvironment with high levels of oxidative stress (OS). This could significantly interfere with the bioactivity of conventional titanium implants, impeding their early osseointegration with bone. We have prepared a series of strontium (Sr)-doped titanium implants via micro-arc oxidation (MAO) to verify their efficacy and differences in osteoinduction capabilities under normal and osteoporotic (high OS levels) conditions. Apart from the chemical composition, all groups exhibited similar physicochemical properties (morphology, roughness, crystal structure, and wettability). Among the groups, the low Sr group (Sr25%) was more conducive to osteogenesis under normal conditions. In contrast, by increasing the catalase (CAT)/superoxide dismutase (SOD) activity and decreasing ROS levels, the high Sr-doped samples (Sr75% and Sr100%) were superior to Sr25% in inducing osteogenic differentiation of MC3T3-E1 cells and the M2 phenotype polarization of RAW264.7 cells, thus enhancing early osseointegration. Furthermore, the results of both in vitro cell co-culture and in vivo studies also showed that the high Sr-doped samples (especially Sr100%) had positive effects on osteoimmunomodulation under the OS microenvironment. Ultimately, the collated findings indicated that the high proportion Sr-doped MAO coatings were more favorable for osteoporosis patients in implant restorations.

Improving the valence self-reversible conversion of cerium nanoparticles on titanium implants by lanthanum doping to enhance ROS elimination and osteogenesis.

Equipped with anti-oxidative properties, cerium oxide nanoparticles (CNPs) are gradually being adopted over the years in the field of oxidative stress research. However, the effects of CNPs may be diminished when under the influence of prolonged and substantially elevated levels of oxidative stress. Therefore, it is imperative to enhance the efficacy of CNPs to resist oxidative stress. In this study, our approach involves the fabrication of titanium surface CNPs coatings doped with different concentrations of lanthanum ions (La3+) and the investigation of their local anti-oxidative stress potential. The physicochemical characterization showed that the La-CNPs groups had a substantial increase in the generation of oxygen vacancies within the CNPs structure with the increase of La doping concentration. In vitro findings proofed that the cytocompatibility of different La-CNPs coatings showed a trend of increasing first and then decreasing with the increase of La doping concentration under oxidative stress microenvironment. Among these groups, the 30 % La-CNPs group presented the best cell proliferation and osteogenic differentiation which could activate the FoxO1 pathway, then upregulated the expression of SOD1 and CAT, and finally resulted in the inhibition of ROS production. In vivo results further confirmed that the 30 % La-CNPs group showed significant osteogenic effects in two rat models (osteoporosis and diabetes models). In conclusion, we believe that the 30 % La-CNPs coating holds promising potential for its implant applications in patients with oxidative stress-related diseases.

Osteoinduction Evaluation of Fluorinated Hydroxyapatite and Tantalum Composite Coatings on Magnesium Alloys.

Magnesium (Mg) alloys have a wide range of biomaterial applications, but their lack of biocompatibility and osteoinduction property impedes osteointegration. In order to enhance the bioactivity of Mg alloy, a composite coating of fluorinated hydroxyapatite (FHA) and tantalum (Ta) was first developed on the surface of the alloy through thermal synthesis and magnetron sputtering technologies in this study. The samples were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive spectroscopy (EDS) mapping, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and water contact angle measurement (WCA), which characterized the surface alternation and confirmed the deposition of the target FHA/Ta coating. The results of cell morphology showed that the MC3T3-E1 cells on the surface of Mg/FHA/Ta samples had the largest spreading area and lamellipodia. Moreover, the FHA coating endowed the surface with superior cell viability and osteogenic properties, while Ta coating played a more important role in osteogenic differentiation. Therefore, the combination of FHA and Ta coatings could synergistically promote biological functions, thus providing a novel strategy for implant design.

Effects of titanium with different micro/nano structures on the ability of osteoblasts to resist oxidative stress.

Excessive accumulation of oxidative intermediates in the elderly significantly aggravates bone degradation and hinders the osseointegration of topological titanium (Ti) implants. Thus, it is of great significance to evaluate the antioxidant and osteoinduction capabilities of various nano, micro or micro/nano-composite structures under oxidative stress (OS) microenvironment. In this study, we discovered that 110 nm titania nanotubes (TNTs) enhanced the adsorption of fibronectin (FN) proteins onto smooth and rough titanium surfaces to varying degrees. Compared with Ti and 30 nm TNTs (T30) groups, cells on 110 nm TNTs (T110), microstructure/30 nm TNTs (M30) and microstructure/110 nm TNTs (M110) had smaller area, lower reactive oxygen species (ROS), and better proliferation/osteogenic differentiation abilities under OS condition, but there was no significant difference among the three groups. In addition, combined with our previous study, we suggested that T110, M30 and M110 resistance to OS was also strongly associated with the high expression of FN-receptor integrin α5 or ß1. All the findings indicated that the micro/nano-composed structures (M30 & M110) had similar anti-oxidation and osteogenesis abilities to T110, which provided guidance for the application of different titanium implants with different topologies in the elderly.

JK-2 loaded electrospun membrane for promoting bone regeneration.

Hydrogen sulfide (H2S) has been as an essential gasotransmitter and a potential therapeutic approach for several biomedical treatments such as cardiovascular disorders, hypertension, and other diseases. The endogenous and exogenous H2S also plays a crucial role in the bone anabolic process and a protective mechanism in cell signalling. In this study, we have utilized two types of polymers, polycaprolactone (PCL) and gelatin (Gel), for the fabrication of JK-2 (H2S donor) loaded nanofibrous scaffold via electrospinning process for bone healing and bone tissue engineering. Comparing the PCL/Gel and PCL/Gel-JK-2 scaffolds, the latter demonstrated enhanced cell adhesion and proliferation capabilities. Furthermore, both experimental scaffolds have been subjected to an in vivo experiment for 4 and 8 weeks in a bone-defect model of a rabbit to determine their biological responses under physiological conditions. There was an obvious increase in bone regeneration in the PCL/Gel-JK-2 group compared to the control and PCL/Gel groups. These results indicate the use of PCL/Gel scaffolds loaded with JK-2 should be considered for possible bone regeneration.

Preparation of Zirconium Hydrogen Phosphate Coatings on Sandblasted/Acid-Etched Titanium for Enhancing Its Osteoinductivity and Friction/Corrosion Resistance.

BACKGROUND: Sandblasted/acid-etched titanium (SLA-Ti) implants are widely used for dental implant restoration in edentulous patients. However, the poor osteoinductivity and the large amount of Ti particles/ions released due to friction or corrosion will affect its long-term success rate. PURPOSE: Various zirconium hydrogen phosphate (ZrP) coatings were prepared on SLA-Ti surface to enhance its friction/corrosion resistance and osteoinduction. METHODS: The mixture of ZrCl4 and H3PO4 was first coated on SLA-Ti and then calcined at 450°C for 5 min to form ZrP coatings. In addition to a series of physiochemical characterization such as morphology, roughness, wettability, and chemical composition, their capability of anti-friction and anti-corrosion were further evaluated by friction-wear test and by potential scanning. The viability and osteogenic differentiation of MC3T3-E1 cells on different substrates were investigated via MTT, mineralization and PCR assays. RESULTS: The characterization results showed that there were no significant changes in the morphology, roughness and wettability of ZrP-modified samples (SLA-ZrP0.5 and SLA-ZrP0.7) compared with SLA group. The results of electrochemical corrosion displayed that both SLA-ZrP0.5 and SLA-ZrP0.7 (especially the latter) had better corrosion resistance than SLA in normal saline and serum-containing medium. SLA-ZrP0.7 also exhibited the best friction resistance and great potential to enhance the spreading, proliferation and osteogenic differentiation of MC3T3-E1 cells. CONCLUSION: We determined that SLA-ZrP0.7 had excellent comprehensive properties including anti-corrosion, anti-friction and osteoinduction, which made it have a promising clinical application in dental implant restoration.