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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. This review provides a concise yet comprehensive summary on the recent progress in the development of metalorganic framework (MOF) coating for the modification of titanium‐based orthopedic implants. Pro‐osseointegration benefit of MOF coatings is discussed in‐depth according to their physical, biochemical, and drug delivery potential, which may facilitate the development of more advanced orthopedic implants with enhanced fracture‐healing capacity and safety.

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. An H2S‐releasing montmorillonite nanoformulation (DPs@MMT) is developed by adsorbing diallyl trisulfide‐loaded peptide dendrimer nanogels onto the MMT surface. DPs@MMT can remodel intestinal mucosal immune homeostasis by activating Nrf2/HO‐1 and PI3K‐AKT pathways, inhibiting p38/ERK MAPK, p65 NF‐κB, and JAK‐STAT3 pathways along with HIF‐1‐induced glycolysis; repair mucosal barrier by activating RAS/MAPK/AP‐1 pathway; and modulate gut microbiota by eliminating pathogens and increasing probiotics.

Guided bone regeneration (GBR) is a critical regenerative strategy for repairing periodontal tissues and craniofacial bone defects. It can establish space to prevent undesirable soft tissue invasion and improve bone regeneration. However, commercially available GBR membranes have some disadvantages in terms of biocompatibility and antibacterial efficacy. Hence, we prepared a polycaprolactone (PCL) membrane by electrospinning and then in situ synthesized vancomycin-assisted zeolitic imidazolate framework-8 (Van-ZIF-8) nanoparticles on its surface. With the formation of Van-ZIF-8, the mechanical properties of the PCL membrane were significantly enhanced. Moreover, the release rates of Van and zinc ions (Zn 2+ ) showed pH responsiveness. In an acidic environment (pH 5.4), the fast hydrolysis of Van-ZIF-8 led to the rapid release of Van and Zn 2+ . The PCL/Van-ZIF-8 membrane exhibited enhanced antibacterial activity against both aerobic and anaerobic bacteria, including Staphylococcus aureus, Escherichia coli, Porphyromonas gingivalis , and Streptococcus mutans , through the hydrolysis of Van-ZIF-8 nanoparticles. Furthermore, the in vitro results for MC3T3-E1 and L929 cells, including cell viability, alkaline phosphatase activity, mineralization level, collagen secretion, gene expression, and fluorescence staining, demonstrated that the PCL/Van-ZIF-8 membrane possessed excellent osteoinductive capacity and could act as an ideal physical barrier to fibroblast growth. Graphical Abstract Schematic illustration of the PCL/Van-Zif-8 electrospinning membrane fabrication and its promotion of mechanical, osteogenesis, and antibacterial properties.

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-1β. 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-1β in endothelium. Overexpression of NFAT5 activates NLRP3-inflammasome and increases the secretion of IL-1β in ECs partly via ROS. Chromatin immunoprecipitation assay demonstrates that NFAT5 directly binds to the promoter regions of NLRP3 and IL-1β 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.

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. Polaprezinc (PZ) was loaded into polycaprolactone/gelatin (PG) hybrid electrospun nanofibers to fabricate a GBR membrane with antioxidant and osteogenesis ability. 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. 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. PZ-loaded degradable PG membranes (especially PG/0.4%PZ) have great potential to accelerate bone regeneration in oxidative stress-related diseases.

Large-diameter titanium dioxide nanotubes (TNTs) have shown promise in preserving osteoblast function under oxidative stress (OS) in vitro. However, their ability to enhance osteogenesis in vivo under OS conditions and the underlying mechanisms remain unclear. This study aimed to evaluate the osteogenic potential of 110 nm TNTs (TNT110) compared to 30 nm TNTs (TNT30) in an aging rat model exhibiting OS, and to investigate the mechanisms involved. Surface properties of TNTs were characterized, and in vitro and in vivo experiments were conducted to assess their osteoinductive effects under OS. Transcriptomic, proteomic analyses, and Western blotting were performed to investigate the protective mechanisms of TNT110 on osteoblasts. Protein adsorption studies focused on the roles of fibronectin (FN) and albumin (BSA) in modulating osteoblast behavior on TNT110. In both in vitro and in vivo experiments, TNT110 significantly improved new bone formation and supported osteoblast survival under OS conditions. Subsequent ribonucleic acid sequencing results indicated that TNT110 tended to attenuate inflammatory responses and reactive oxygen species (ROS) expression while promoting endoplasmic reticulum (ER) stress and extracellular matrix receptor interactions, all of which are crucial for osteoblast survival and functionality. Further confirmation indicated that the cellular behavior changes of osteoblasts in the TNT110 group could only occur in the presence of serum. Moreover, proteomic analysis under OS conditions revealed the pivotal roles of FN and BSA in augmenting TNT110's resistance to OS. Surface pretreatment of TNT110 with FN/BSA alone could beneficially influence the early adhesion, spreading, ER activity, and ROS expression of osteoblasts, a trend not observed with TNT30. TNT110 effectively protects osteoblast function in the OS microenvironment by modulating protein adsorption, with FN and BSA synergistically enhancing osteogenesis. These findings suggest TNT110's potential for use in implants for elderly patients.

Many studies have shown that the size of nanotube (NT) can significantly affect the behavior of osteoblasts on titanium-based materials. But the weak bonding strength between NT and substrate greatly limits their application.  The objective of this study was to compare the stability of NT and nanopore (NP) coatings, and further prepare antibacterial titanium-based materials by loading LL37 peptide in NP structures.  The adhesion strength of NT and NP layers was investigated using a scratch tester. The proliferation and differentiation of MC3T3-E1 cells on different substrates were evaluated in vitro by CCK8, alkaline phosphatase activity, mineralization and polymerase chain reaction assays. The antibacterial rates of NP and NP/LL37 were also measured by spread plate method. Moreover, the osteogenesis around NP and NP/LL373 in vivo was further evaluated using uninfected and infected models.  Scratch test proved that the NP layers had stronger bonding strength with the substrates due to their continuous pore structures and thicker pipe walls than the independent NT structures. In vitro, cell results showed that MC3T3-E1 cells on NP substrates had better early adhesion, spreading and osteogenic differentiation than those of NT group. In addition, based on the drug reservoir characteristics of porous materials, the NP substrates were also used to load antibacterial LL37 peptide. After loading LL37, the antibacterial and osteogenic induction abilities of NP were further improved, thus significantly promoting osteogenesis in both uninfected and infected models.  We determined that the NP layers had stronger bonding strength than NT structures, and the corresponding NP materials might be more suitable than NT for preparing drug-device combined titanium implants for bone injury treatment.

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 (Si 3 N 4 ) 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 Si 3 N 4 -doped materials showed excellent angiogenesis properties, including the promotion of cell migration and tubule formation, which play essential roles in early recovery after implantation.

Antibacterial and osteogenic functionalization of titanium (Ti) implants will greatly expand their clinical indications in immediate implant therapy, accelerate osteointegration, and enhance long-term prognosis. We had recently shown that the high-energy shot peening (HESP)-assisted micro-arc oxidation (MAO) significantly improved the bioactivity and coating stability of Ti-based substrates. In this study, we further functionalized Ti with antibacterial and osteogenic properties by doping silicon (Si) and/or copper (Cu) ions into HESP/MAO-treated coatings. Physicochemical characterization displayed that the doping of Si and Cu in HESP/MAO-treated coatings (Si/Cu-MAO) did not significantly change their surface topography, roughness, crystal structure, coating thickness, bonding strength, and wettability. The results of X-ray photoelectron spectroscopy (XPS) showed that Si and Cu in the Si/Cu-MAO coating was in the form of silicate radical (SiO32–) and bivalent copper (Cu2+), respectively. The total amounts of Si and Cu were about 13.5 and 5.8 μg/cm2, which released about 33.2 and 31.3% within 14 day, respectively. Compared with the control group (MAO), Si doping samples (MAO-Si) significantly increased the cell viability, alkaline phosphatase (ALP) activity, mineralization and osteogenic genes (ALP, collagen I and osteocalcin) expression of MC3T3-E1 cells. Furthermore, the addition of Cu presented good bactericidal property against both Staphylococcus aureus and Streptococcus mutans (even under the co-culture condition of bacteria and MC3T3-E1 cells): the bacteriostatic rate of both bacteria was over 95%. In conclusion, the novel bioactive Si/Cu-MAO coating with antibacterial and osteogenic properties is a promising functionalization method for orthopedic and dental implants, especially in the immediate implant treatment with an infected socket.

Yttria-stabilized zirconia (YSZ) is widely used in dental implants and prostheses due to its excellent aesthetic and restorative properties. However, its bio-inert surface limits early osseointegration and weakens bonding strengths with porcelain veneer/resin cement. Inspired by the structure of beetle elytra, this work proposes a novel strategy involving a self-assembled trabecular-honeycomb biomimetic zirconium phosphate (ZrP) nanonetwork to modify YSZ surfaces. This approach simultaneously enhances energy dissipation, interfacial bonding, and osseointegration. The pore size of ZrP nanonetwork was precisely controlled by adjusting reaction temperatures (120 °C and 160 °C) and phosphoric acid concentrations (1.0 wt% and 2.5 wt%). Compared to conventional YSZ, the ZrP nanonetworks achieved remarkable improvements in bond strength, showing increases of 111 % with porcelain veneer and 336 % with resin cement. These enhancements are attributed to multiscale physical-chemical-mechanical interactions, including micromechanical anchoring, chemical bonding via phosphate groups, and energy dissipation through topological optimization. In vitro studies demonstrated that large-pore-size nanonetworks promote osteogenic differentiation of osteoblasts and modulate macrophage polarization toward the M2 phenotype, fostering an immune environment conducive to bone regeneration. In vivo experiments further validated the superior osseointegration and bone regeneration capacities of the large-pore-size ZrP nanonetwork. Collectively, this biomimetic ZrP nanonetwork-modified YSZ, with its exceptional physical-chemical-mechanical bonding properties, osseointegration potential, and immune-modulating capabilities, represents a groundbreaking advancement in zirconia-based material for dental implants and prostheses. Schematic illustration of the biomimetic damping layer of trabecula-honeycomb zirconium phosphate (ZrP) nanonetwork structure on zirconia surface, mimicking the structure and biological characteristics of beetle elytra, which provides superior interfacial bonding strength and osteogenic properties for zirconia-based restorations and implants. [Display omitted] •Bioinspired trabecular-honeycomb ZrP nanonetworks self-assemble onto zirconia.•The pore sizes are controlled by reaction temperature and phosphoric acid concentration.•ZrP layer strengthens veneer/resin-zirconia bonding by energy dissipation and mechanochemical interactions.•ZrP nanonetworks exert pro-osteogenic and anti-inflammatory effects.