Effect of Nitrogen Doping on the Photocatalytic Properties and Antibiofilm Efficacy of Reduced TiO2 Nanoparticles.

Nanomaterial-mediated antibacterial photodynamic therapy (aPDT) emerges as a promising treatment against antibiotic-resistant bacterial biofilms. Specifically, titanium dioxide nanoparticles (TiO2 NPs) are being investigated as photosensitizers in aPDT to address biofilm related diseases. To enhance their photocatalytic performance in the visible spectral range for biomedical applications, various strategies have been adopted, including reduction of TiO2 NPs. However, despite improvements in visible-light photoactivity, reduced TiO2 NPs have yet to reach their expected performance primarily due to the instability of oxygen vacancies and their tendency to reoxidize easily. To address this, we present a two-step approach to fabricate highly visible-light active and stable TiO2 NP photocatalysts, involving nitrogen doping followed by a magnesium-assisted reductive annealing process. X-ray photoelectron spectroscopy analysis of the synthesized reduced nitrogen-doped TiO2 NPs (H:Mg-N-TiO2 NPs) reveals that the presence of nitrogen stabilizes oxygen vacancies and reduced Ti species, leading to increased production of reactive oxygen species under visible-light excitation. The improved aPDT efficiency translates to a 3-fold enhancement in the antibiofilm activity of nitrogen-doped compared to undoped reduced TiO2 NPs against both Gram-positive (Streptococcus mutans) and Gram-negative (Porphyromonas gingivalis, Fusobacterium nucleatum) oral pathogens. These results underscore the potential of H:Mg-N-TiO2 NPs in aPDT for combating bacterial biofilms effectively.

Optimized Electrophoretic Deposition of Chitosan/Mesoporous Glass Nanoparticles with Gentamicin on Titanium Implants: Enhancing Hemocompatibility and Antibacterial Activity.

Titanium-based implants have long been studied and used for applications in bone tissue engineering, thanks to their outstanding mechanical properties and appropriate biocompatibility. However, many implants struggle with osseointegration and attachment and can be vulnerable to the development of infections. In this work, we have developed a composite coating via electrophoretic deposition, which is both bioactive and antibacterial. Mesoporous bioactive glass particles with gentamicin were electrophoretically deposited onto a titanium substrate. In order to validate the hypothesis that the quantity of particles in the coatings is sufficiently high and uniform in each deposition process, an easy-to-use image processing algorithm was designed to minimize human dependence and ensure reproducible results. The addition of loaded mesoporous particles did not affect the good adhesion of the coating to the substrate although roughness was clearly enhanced. After 7 days of immersion, the composite coatings were almost dissolved and released, but phosphate-related compounds started to nucleate at the surface. With a simple and low-cost technique like electrophoretic deposition, and optimized stir and suspension times, we were able to synthesize a hemocompatible coating that significantly improves the antibacterial activity when compared to the bare substrate for both Gram-positive and Gram-negative bacteria.

Study on the Antibacterial Activity and Bone Inductivity of Nanosilver/PLGA-Coated TI-CU Implants.

Background: Implants are widely used in the field of orthopedics and dental sciences. Titanium (TI) and its alloys have become the most widely used implant materials, but implant-associated infection remains a common and serious complication after implant surgery. In addition, titanium exhibits biological inertness, which prevents implants and bone tissue from binding strongly and may cause implants to loosen and fall out. Therefore, preventing implant infection and improving their bone induction ability are important goals. Purpose: To study the antibacterial activity and bone induction ability of titanium-copper alloy implants coated with nanosilver/poly (lactic-co-glycolic acid) (NSPTICU) and provide a new approach for inhibiting implant-associated infection and promoting bone integration. Methods: We first examined the in vitro osteogenic ability of NSPTICU implants by studying the proliferation and differentiation of MC3T3-E1 cells. Furthermore, the ability of NSPTICU implants to induce osteogenic activity in SD rats was studied by micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, masson staining, immunohistochemistry and van gieson (VG) staining. The antibacterial activity of NSPTICU in vitro was studied with gram-positive Staphylococcus aureus (Sa) and gram-negative Escherichia coli (E. coli) bacteria. Sa was used as the test bacterium, and the antibacterial ability of NSPTICU implanted in rats was studied by gross view specimen collection, bacterial colony counting, HE staining and Giemsa staining. Results: Alizarin red staining, alkaline phosphatase (ALP) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis showed that NSPTICU promoted the osteogenic differentiation of MC3T3-E1 cells. The in vitro antimicrobial results showed that the NSPTICU implants exhibited better antibacterial properties. Animal experiments showed that NSPTICU can inhibit inflammation and promote the repair of bone defects. Conclusion: NSPTICU has excellent antibacterial and bone induction ability, and has broad application prospects in the treatment of bone defects related to orthopedics and dental sciences.

Titania-Graphene Oxide Nanocomposite-Based Philadelphia-Positive Leukemia Therapy.

Philadelphia-positive (Ph+) leukemia is a type of blood cancer also known as acute lymphoblastic leukemia (ALL), affecting 20-30% of adults diagnosed worldwide and having an engraved prognosis as compared to other types of leukemia. The current treatment regimens mainly rely on tyrosine kinase inhibitors (TKIs) and bone marrow transplants. To date, several generations of TKIs have been developed due to associated resistance and frequent relapse, with cardiovascular system anomalies being the most devastating complication. Nanotechnology has the potential to address these limitations by the targeted drug delivery and controlled release of TKIs. This study focused on the titanium dioxide (TiO2) and graphene oxide (GO) nanocomposite employment to load nilotinib and ponatinib TKIs for therapy of Ph+ leukemia cell line (K562) and Ba/F3 cells engineered to express BCR-ABL oncogene. Meanwhile, after treatment, the oncogene expressing fibroblast cells (Rat-1 P185) were evaluated for their colony formation ability under 3D conditions. To validate the nanocomposite formation, the TiO2-GO nanocomposites were characterized by scanning electron microscope, DLS, XRD, FTIR, zeta potential, EDX, and element mapping. The TKI-loaded TiO2-GO was not inferior to the free drugs after evaluating their effects by a cell viability assay (XTT), apoptosis induction, and colony formation inhibition. The cell signaling pathways of the mammalian target of rapamycin (mTOR), signal transducers and activators of transcription 5 (STAT5), and extracellular signal-regulated kinase (Erk1/2) were also investigated by Western blot. These signaling pathways were significantly downregulated in the TKI-loaded TiO2-GO-treated groups. Based on the findings above, we can conclude that TiO2-GO exhibited excellent drug delivery potential that can be used for Ph+ leukemia therapy in the future, subject to further investigations.

Apoptotic bodies encapsulating Ti2N nanosheets for synergistic chemo-photothermal therapy.

Extracellular vesicles (EVs) have great potential in oncology drug delivery because of their unique biological origin. Apoptotic bodies (ABs), as a member of the EV family, offer distinct advantages in terms of size, availability and membrane properties, but have been neglected for a long time. Here, using ABs and Ti2N nanosheets, we propose a novel drug delivery system (Ti2N-DOX@ABs), which exhibit a homologous targeting ability for dual-strategy tumor therapy with intrinsic biological property. The experimental results demonstrate that such a drug delivery system possesses a drug loading capacity of 496.5% and a near-infrared photothermal conversion efficiency of 38.4%. In addition, the investigation of drug internalization process proved that Ti2N-DOX@ABs featured a supreme biocompatibility. Finally, the dual-strategy response based on photothermal and chemotherapeutic effects was studied under near-infrared laser radiation. This work explores the opportunity of apoptosome membranes in nanomedicine systems, which provides a technical reference for cancer-oriented precision medicine research.

Calcium phosphate graphene and Ti3C2Tx MXene scaffolds with osteogenic and antibacterial properties.

Bioactive degradable scaffolds that facilitate bone healing while fighting off initial bacterial infection have the potential to change established strategies of dealing with traumatic bone injuries. To achieve this a composite material made from calcium phosphate graphene (CaPG), and MXene was synthesized. CaPG was created by functionalizing graphene oxide with phosphate groups in the presence of CaBr with a Lewis acid catalyst. Through this transformation, Ca2+ and PO4 3- inducerons are released as the material degrades thereby aiding in the process of osteogenesis. The 2D MXene sheets, which have shown to have antibacterial properties, were made by etching the Al from a layered Ti3AlC2 (MAX phase) using HF. The hot-pressed scaffolds made of these materials were designed to combat the possibility of infection during initial surgery and failure of osteogenesis to occur. These two failure modes account for a large percentage of issues that can arise during the treatment of traumatic bone injuries. These scaffolds were able to retain induceron-eluting properties in various weight percentages and bring about osteogenesis with CaPG alone and 2 wt% MXene scaffolds demonstrating increased osteogenic activity as compared to no treatment. Additionally, added MXene provided antibacterial properties that could be seen at as little as 2 wt%. This CaPG and MXene composite provides a possible avenue for developing osteogenic, antibacterial materials for treating bone injuries.

SrTiO3 Nanotube-Based "Pneumatic Nanocannon" for On-Demand Delivery of Antibacterial and Sustained Osseointegration Enhancement.

Infection and aseptic loosening caused by bacteria and poor osseointegration remain serious challenges for orthopedic implants. The advanced surface modification of implants is an effective strategy for addressing these challenges. This study presents a "pneumatic nanocannon" coating for titanium orthopedic implants to achieve on-demand release of antibacterial and sustained release of osteogenic agents. SrTiO3 nanotubes (SrNT) were constructed on the surface of Ti implants as "cannon barrel," the "cannonball" (antibiotic) and "propellant" (NH4HCO3) were codeposited into SrNT with assistance of mussel-inspired copolymerization of dopamine and subsequently sealed by a layer of polydopamine. The encapsulated NH4HCO3 within the nanotubes could be thermally decomposed into gases under near-infrared irradiation, propelling the on-demand delivery of antibiotics. This coating demonstrated significant efficacy in eliminating typical pathogenic bacteria both in planktonic and biofilm forms. Additionally, this coating exhibited a continuous release of strontium ions, which significantly enhanced the osteogenic differentiation of preosteoblasts. In an implant-associated infection rat model, this coating demonstrated substantial antibacterial efficiency (>99%) and significant promotion of osseointegration, along with alleviated postoperative inflammation. This pneumatic nanocannon coating presents a promising approach to achieving on-demand infection inhibition and sustained osseointegration enhancement for titanium orthopedic implants.

Nongenetic Precise Neuromodulation and Spatiotemporal Neuroprotection for Epilepsy Therapy via Rationally Designed Multifunctional Nanotransducer.

The precise modulation of electrical activity in specific neuronal populations is paramount for rectifying abnormal neurological functions and is a critical element in the therapeutic arsenal for neurological disorders. However, achieving a balance between minimal invasiveness and robust neuroprotection poses a considerable challenge. Herein, we present a nanoneuromodulation strategy integrating neuroprotective features to effectively address epilepsy with minimal invasiveness and enable wireless functionality. Strategically engineered nanotransducer, adorned with platinum (Pt) decoration with titanium disulfide (TiS2) (TiS2/Pt), enables precise modulation of neuronal electrical activity in vitro and in vivo, ensuring exceptional temporal fidelity under millisecond-precision near-infrared (NIR) light pulses irradiation. Concurrently, TiS2/Pt showcase a pronounced enhancement in enzyme-mimicking activity, offering a robust defense against oxidative neurological injury in vitro. Nanotransducer-enabled wireless neuromodulation with biocatalytic neuroprotective capacity is highly effective in alleviating epileptic high-frequency neural activity and diminishing oxidative stress levels, thereby restoring redox equilibrium. This integrated therapeutic approach reduces the severity of epilepsy, demonstrating minimal invasiveness and obviating the requirements for genetic manipulation and optical fiber implantation, while providing an alternative avenue for neurological disorder treatment.

Comparative Analysis of Osteoblastic Responses to Titanium and Alumina-Toughened Zirconia Implants: An In Vitro Study.

INTRODUCTION: Osteoblastic responses play a crucial role in the success of oral implants. Enhanced proliferation of osteoblast cells is associated with reduced cell mortality and an increase in bone regeneration. This study aims to evaluate the osteoblastic responses following oral implantation. MATERIALS AND METHODS: Osteoblast stem cells were harvested and subsequently cultivated using cell culture techniques. The osteoblastic phenotype of the extracted cells was confirmed by examining the extracellular matrix. Cell morphogenesis on functionalized biomaterial surfaces was assessed through indirect immunofluorescence staining. The cellular response was investigated in the presence of two types of implant materials: titanium (Ti) and alumina-toughened zirconia (ATZ). Cell viability and apoptosis were quantitatively assessed using MTT assays and flow cytometry, respectively. RESULTS: The survival of osteoblastic lineage cells was moderately reduced post-implantation. Viability in the Ti implant group remained at approximately 86%, while in the ATZ group, it was observed at 75%, which is considered acceptable. Moreover, there was a significant disparity in cell survival between the two implant groups (p < 0.05). Analysis of apoptosis levels at various concentrations revealed that the rate of apoptosis was 3.6% in the control group and 18.5% in the ATZ group, indicating that apoptosis or programmed cell death in the ATZ-treated group had increased nearly four-fold (p < 0.05). CONCLUSIONS: The findings of this study indicate a reduction in osteoblastic cell line survival following implant treatment, with titanium implants exhibiting superior performance in terms of cell survival. However, it was also noted that the incidence of apoptosis in osteoblast cells was significantly higher in the presence of zirconium-based implants.

Research Progress on Ti3C2Tx-Based Composite Materials in Antibacterial Field.

The integration of two-dimensional Ti3C2Tx nanosheets and other materials offers broader application options in the antibacterial field. Ti3C2Tx-based composites demonstrate synergistic physical, chemical, and photodynamic antibacterial activity. In this review, we aim to explore the potential of Ti3C2Tx-based composites in the fabrication of an antibiotic-free antibacterial agent with a focus on their systematic classification, manufacturing technology, and application potential. We investigate various components of Ti3C2Tx-based composites, such as metals, metal oxides, metal sulfides, organic frameworks, photosensitizers, etc. We also summarize the fabrication techniques used for preparing Ti3C2Tx-based composites, including solution mixing, chemical synthesis, layer-by-layer self-assembly, electrostatic assembly, and three-dimensional (3D) printing. The most recent developments in antibacterial application are also thoroughly discussed, with special attention to the medical, water treatment, food preservation, flexible textile, and industrial sectors. Ultimately, the future directions and opportunities are delineated, underscoring the focus of further research, such as elucidating microscopic mechanisms, achieving a balance between biocompatibility and antibacterial efficiency, and investigating effective, eco-friendly synthesis techniques combined with intelligent technology. A survey of the literature provides a comprehensive overview of the state-of-the-art developments in Ti3C2Tx-based composites and their potential applications in various fields. This comprehensive review covers the variety, preparation methods, and applications of Ti3C2Tx-based composites, drawing upon a total of 171 English-language references. Notably, 155 of these references are from the past five years, indicating significant recent progress and interest in this research area.

Enhancing the Biological Performance of Titanium Alloy through In Situ Modulation of the Surface Nanostructure: Near-Infrared-Responsive Antibacterial Function and Osteoinductivity.

The poor clinical performance of titanium and its alloy implants is mainly attributed to their lack of antibacterial ability and poor osseointegration. The key and challenge lie in how to enhance their osteoinductivity while imparting antibacterial capability. In this study, a titanium oxide metasurface with light-responsive behavior was constructed on the surface of titanium alloy using an alkaline-acid bidirectional hydrothermal method. The effects of the acid type, acid concentration, hydrothermal time, hydrothermal temperature, and subsequent heat treatments on the optical behavior of the metasurface were systematically investigated with a focus on exploring the influence of the metasurface and photodynamic reaction on the osteogenic activity of osteoblasts. Results show that the type of acid and heat treatment significantly affect the light absorption of the titanium alloy surface, with HCl and post-heat-treatment favoring redshift in the light absorption. Under 808 nm near-infrared (NIR) irradiation for 10 min, in vitro antibacterial experiments demonstrate that the antibacterial rate of the metasurface titanium alloy against Staphylococcus aureus and Escherichia coli were 96.87% and 99.27%, respectively. In vitro cell experiments demonstrate that the nanostructure facilitates cell adhesion, proliferation, differentiation, and expression of osteogenic-related genes. Surprisingly, the nanostructure promoted the expression of relevant osteogenic genes of MC3T3-E1 under 808 nm NIR irradiation. This study provides a method for the surface modification of titanium alloy implants.

Studying the impact of titanium dioxide nanoparticles on the expression of pivotal genes related to menthol biosynthesis and certain biochemical parameters in peppermint plants (Mentha Piperita L.).

BACKGROUND: This study examines the impact of titanium dioxide nanoparticles (TiO2NPs) on gene expression associated with menthol biosynthesis and selected biochemical parameters in peppermint plants (Mentha piperita L.). Menthol, the active ingredient in peppermint, is synthesized through various pathways involving key genes like geranyl diphosphate synthase, menthone reductase, and menthofuran synthase. Seedlings were treated with different concentrations of TiO2NPs (50, 100, 200, and 300 ppm) via foliar spray. After three weeks of treatment, leaf samples were gathered and kept at -70 °C for analysis. RESULTS: According to our findings, there was a significant elevation (P ≤ 0.05) in proline content at concentrations of 200 and 300 ppm in comparison with the control. Specifically, the highest proline level was registered at 200 ppm, reaching 259.64 ± 33.33 µg/g FW. Additionally, hydrogen peroxide and malondialdehyde content exhibited a decreasing trend following nanoparticle treatments. Catalase activity was notably affected by varying TiO2NP concentrations, with a significant decrease observed at 200 and 300 ppm compared to the control (P ≤ 0.05). Conversely, at 100 ppm, catalase activity significantly increased (11.035 ± 1.12 units/mg of protein/min). Guaiacol peroxidase activity decreased across all nanoparticle concentrations. Furthermore, RT-qPCR analysis indicated increased expression of the studied genes at 300 ppm concentration. CONCLUSIONS: Hence, it can be inferred that at the transcript level, this nanoparticle exhibited efficacy in influencing the biosynthetic pathway of menthol.

3D Printed Pedicle Screws with Microarc Oxidation Ceramic Interfaces Enhance Osteointegration and Orthopedic Fixation Feasibility.

Effective osteointegration is of great importance for pedicle screws in spinal fusion surgeries. However, the lack of osteoinductive activity of current screws diminishes their feasibility for osteointegration and fixation, making screw loosening a common complication worldwide. In this study, Ti-6Al-4V pedicle screws with full through-hole design were fabricated via selective laser melting (SLM) 3D printing and then deposited with porous oxide coatings by microarc oxidation (MAO). The porous surface morphology of the oxide coating and the release of bioactive ions could effectively support cell adhesion, migration, vascularization, and osteogenesis in vitro. Furthermore, an in vivo goat model demonstrated the efficacy of modified screws in improving bone maturation and osseointegration, thus providing a promising method for feasible orthopedic internal fixation.

Biodegradable MXene Quantum Dots with High Near-Infrared Photothermal Performance for Cancer Treatment.

Photothermal therapy (PTT) offers significant potential in cancer treatment due to its short, simple, and less harmful nature. However, obtaining a photothermal agent (PTA) with good photothermal performance and biocompatibility remains a challenge. MXenes, which are PTAs, have shown promising results in cancer treatment. This study presents the preparation of Ti3C2 MXene quantum dots (MXene QDs) using a simple hydrothermal and ultrasonic method and their use as a PTA for cancer treatment. Compared to conventional MXene QDs synthesized using only the hydrothermal method, the ultrasonic process increased the degree of oxidation on the surface of the MXene QDs. This resulted in the presence of more hydrophilic groups such as hydroxyl groups on the MXene QD surfaces, leading to excellent dispersion in the aqueous system and biocompatibility of the prepared MXene QDs without the need for surface modification. The MXene QDs showed great photothermal performance with a photothermal conversion efficiency of 62.5%, resulting in the highest photothermal conversion efficiency among similar materials reported thus far. Both in vitro and in vivo experiments have proved the potent tumor inhibitory effect of the MXene QD-mediated PTT, with minimal harm to mice. Therefore, these MXene QDs hold a significant promise for clinical applications.

Synthesis and characterization of X (X = Ni or Fe) modified BaTiO3 for effective degradation of Reactive Red 120 dye under UV-A light and its biological activity.

For the sustainable advancement of industrial expansion that is environmentally conscious, harmful dyes must be removed from wastewater. Untreated effluents containing colors have the potential to harm the ecosystem and pose major health risks to people, animals, and aquatic life. Here, we have fabricated Ni or Fe modified with BaTiO3 materials and effectively utilized them for Reactive Red 120 (RR 120) dye degradation under UV-A light. The synthesized materials were characterized, and their structural, and photo-physical properties were reported. Phase segregation was not present in the XRD pattern, as evidenced by the absence of secondary phase peaks linked to iron, nickel, or oxides. Low metal ion concentrations may be the cause of this, and the presence of those elements was confirmed by XPS measurements. The Raman spectra of the BaTiO3/Ni and BaTiO3/Fe samples show a widened peak at 500 cm-1, which suggests that Ni or Fe are efficiently loaded onto the BaTiO3. RR 120 dye photodegradation under UV light conditions was effectively catalyzed by BaTiO3/Fe, as evidenced by its superior performance in the UV irradiation technique over both BaTiO3 and BaTiO3/Ni. Compared to bare BaTiO3, both metal-modified materials efficiently degraded the RR 120 dye. Acidic pH facilitated the degradation process, which makes sense given that the heterogeneous photo-Fenton reaction was the mechanism of degradation along with BaTiO3 sensitization. High-acidity sewage can be dangerous and carcinogenic, and conventional biological treatment methods are not appropriate for managing it. In the current investigation, it may be used to treat color effluents with extremely low pH levels. Additionally, the ability of the produced nanocomposites to inhibit the growth of twenty pathogens was examined, along with two fungi, fifteen Gram-negative Bacilli (GNB), one Gram-positive Bacilli (GPB), and two Gram-positive Cocci (GBC).

Nanoporous Titanium Implant Surface Accelerates Osteogenesis via the Piezo1/Acetyl-CoA/ß-Catenin Pathway.

Osseointegration is the most important factor determining implant success. The surface modification of TiO2 nanotubes prepared by anodic oxidation has remarkable advantages in promoting bone formation. However, the mechanism behind this phenomenon is still unintelligible. Here we show that the nanomorphology exhibited open and clean nanotube structure and strong hydrophilicity, and the nanomorphology significantly facilitated the adhesion, proliferation, and osteogenesis differentiation of stem cells. Exploring the mechanism, we found that the nanomorphology can enhance mitochondrial oxidative phosphorylation (OxPhos) by activating Piezo1 and increasing intracellular Ca2+. The increase in OxPhos can significantly uplift the level of acetyl-CoA in the cytoplasm but not significantly raise the level of acetyl-CoA in the nucleus, which was beneficial for the acetylation and stability of ß-catenin and ultimately promoted osteogenesis. This study provides a new interpretation for the regulatory mechanism of stem cell osteogenesis by nanomorphology.

Titania (TiO2) nanotube surfaces doped with zinc and strontium for improved cell compatibility.

Titanium-based orthopedic implants are gaining popularity in recent years due to their excellent biocompatibility, superior corrosion resistance and lightweight properties. However, these implants often fail to perform effectively due to poor osseointegration. Nanosurface modification approaches may help to resolve this problem. In this work, TiO2 nanotube (NT) arrays were fabricated on commercially available pure titanium (Ti) surfaces by anodization and annealing. Then, zinc (Zn) and strontium (Sr), important for cell signaling, were doped on the NT surface by hydrothermal treatment. This very simple method of Zn and Sr doping takes less time and energy compared to other complicated techniques. Different surface characterization tools such as scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDS), static water contact angle, X-ray diffraction (XRD) and nanoindentation techniques were used to evaluate the modified surfaces. Then, adipose derived stem cells (ADSCs) were cultured with the surfaces to evaluate cell adhesion, proliferation, and growth on the surfaces. After that, the cells were differentiated towards osteogenic lineage to evaluate alkaline phosphatase (ALP) activity, osteocalcin expression, and calcium phosphate mineralization. Results indicate that NT surfaces doped with Zn and Sr had significantly enhanced ADSC adhesion, proliferation, growth, and osteogenic differentiation compared to an unmodified surface, thus confirming the enhanced performance of these surfaces.

The Effect of Antibacterial-Osteogenic Surface Modification on the Osseointegration of Titanium Implants: A Static and Dynamic Strategy.

Titanium (Ti) and its alloys are widely used biomaterials in bone repair. Although these biomaterials possess stable properties and good biocompatibility, the high elastic modulus and low surface activity of Ti implants have often been associated with infection, inflammation, and poor osteogenesis. Therefore, there is an urgent need to modify the surface of Ti implants, where changes in surface morphology or coatings loading can confer specific functions to help them adapt to the osseointegration formation phase and resist bacterial infection. This can further ensure a healthy microenvironment for bone regeneration as well as the promotion of immunomodulation, angiogenesis, and osteogenesis. Therefore, in this review, we evaluated various functional Ti implants after surface modification, both in terms of static modifications and dynamic response strategies, mainly focusing on the synergistic effects of antimicrobial activities and functionalized osteogenic. Finally, the current challenges and future perspectives are summarized to provide innovative and effective solutions for osseointegration and bone defect repair.

Size-Dependent Effect of Titania Nanotubes on Endoplasmic Reticulum Stress to Re-establish Diabetic Macrophages Homeostasis.

In patients with diabetes, endoplasmic reticulum stress (ERS) is a crucial disrupting factor of macrophage homeostasis surrounding implants, which remains an obstacle to oral implantation success. Notably, the ERS might be modulated by the implant surface morphology. Titania nanotubes (TNTs) may enhance diabetic osseointegration. However, a consensus has not been achieved regarding the tube-size-dependent effect and the underlying mechanism of TNTs on diabetic macrophage ERS. We manufactured TNTs with small (30 nm) and large diameters (100 nm). Next, we assessed how the different titanium surfaces affected diabetic macrophages and regulated ERS and Ca2+ homeostasis. TNTs alleviated the inflammatory response, oxidative stress, and ERS in diabetic macrophages. Furthermore, TNT30 was superior to TNT100. Inhibiting ERS abolished the positive effect of TNT30. Mechanistically, topography-induced extracellular Ca2+ influx might mitigate excessive ERS in macrophages by alleviating ER Ca2+ depletion and IP3R activation. Furthermore, TNT30 attenuated the peri-implant inflammatory response and promoted osseointegration in diabetic rats. TNTs with small nanodiameters attenuated ERS and re-established diabetic macrophage hemostasis by inhibiting IP3R-induced ER Ca2+ depletion.

MOF-Derived Oxygen-Deficient Titania-Mediated Photodynamic/Photothermal-Enhanced Immunotherapy for Tumor Treatment.

Immunotherapy has emerged as a revolutionizing therapeutic modality for cancer. However, its efficacy has been largely limited by a weak immune response and an immunosuppressive tumor microenvironment. Herein, we report a metal-organic framework (MOF)-derived titanium oxide nanoparticle (MCTx NP) as an immune booster that can greatly improve the immunotherapy efficacy by inducing "immunogenic cell death" (ICD) and remodeling the tumor microenvironment. The NPs, inheriting the characteristic structure of MIL-125 and enriched with oxygen vacancies (OVs), demonstrate both high photothermal conversion efficiency and a reactive oxygen species (ROS) generation yield upon near-infrared (NIR) activation. Moreover, the NPs can release O2 and reduce glutathione (GSH) in the tumor environment, showcasing their potential to reverse the immunosuppressive microenvironment. In vitro/vivo results demonstrate that MCTx NPs directly kill tumor cells and effectively eliminate primary tumors by exerting dual photodynamic/photothermal therapy under a single NIR irritation. At the same time, MCTx NPs augment the PD-L1 blockade efficacy by potently inducing ICDs and reversing the immunosuppressive tumor microenvironment, including promoting dendritic cell (DC) maturation, decreasing regulatory T cells (Tregs)' infiltration, and increasing cytotoxic T lymphocytes (CTLs) and helper T cells (Ths), resulting in effective distant tumor suppression. This work highlights MCTx NP-mediated photodynamic- and photothermal-enhanced immunotherapy as an effective strategy for tumor treatment.