Vaporization phosphorization-mediated synthesis of phosphorus-doped TiO2 nanocomposites for combined photodynamic and photothermal therapy of renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a disease with high incidence and poor prognosis. The conventional treatment involves radiotherapy and chemotherapy, but chemotherapeutic agents are often associated with side effects, i.e., cytotoxicity to nontumor cells. Therefore, there is an urgent need for the development of novel therapeutic strategies for ccRCC. We synthesized spherical P/TiO2 nanoparticles (P/TiO2 NPs) by vaporization phosphorization (VP). X-ray photoelectron spectroscopy (XPS) and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS) analyses confirmed that the anatase TiO2 surface was successfully doped with phosphorus and produced a large number of oxygen vacancies (OV). Serving as a photosensitizer, P/TiO2 NPs not only extended the photoresponse range to the near-infrared II region (NIR II) but also introduced a donor energy level lower than the TiO2 conduction band, narrowing the band gap, which could facilitate the migration of photogenerated charges and trigger the synergistic treatment of photodynamic therapy (PDT) and photothermal therapy (PTT). During NIR irradiation in vitro, the P/TiO2 NPs generated local heat and various oxygen radicals, including 1O2, ˙O2-, H2O2, and ˙OH, which damaged the ccRCC cells. In vivo, administration of the P/TiO2 NPs + NIR reduced the tumor volume by 80%, and had the potential to inhibit tumor metastasis by suppressing intratumor neoangiogenesis. The P/TiO2 NPs showed superior safety and efficacy relative to the conventional chemotherapeutic agent used in ccRCC treatment. This study introduced an innovative paradigm for renal cancer treatment, highlighting the potential of P/TiO2 NPs as safe and effective nanomaterials and presenting a compelling new option for clinical applications in anticancer therapy.

Exogenous titanium dioxide nanoparticles alleviate cadmium toxicity by enhancing the antioxidative capacity of Tetrastigma hemsleyanum.

Nanotechnology is one of the most recent approaches employed to defend plants against both biotic and abiotic stress including heavy metals such as Cadmium (Cd). In this study, we evaluated the effects of titanium dioxide (TiO2) nanoparticles (TiO2 NPs) in alleviating Cd stress in Tetrastigma hemsleyanum Diels et Gilg. Compared with Cd treatment, TiO2 NPs decreased leaf Cd concentration, restored Cd exposure-related reduction in the biomass to about 69% of control and decreased activities of antioxidative enzymes. Integrative analysis of transcriptome and metabolome revealed 325 differentially expressed genes associated with TiO2 NP treatment, most of which were enriched in biosynthesis of secondary metabolites. Among them, the flavonoid and phenylpropanoid biosynthetic pathways were significantly regulated to improve the growth of T. hemsleyanum when treated with Cd. In the KEGG Markup Language (KGML) network analysis, we found some commonly regulated pathways between Cd and Cd+TiO2 NP treatment, including phenylpropanoid biosynthesis, ABC transporters, and isoflavonoid biosynthesis, indicating their potential core network positions in controlling T. hemsleyanum response to Cd stress. Overall, our findings revealed a complex response system for tolerating Cd, encompassing the transportation, reactive oxygen species scavenging, regulation of gene expression, and metabolite accumulation in T. hemsleyanum. Our results indicate that TiO2 NP can be used to reduce Cd toxicity in T. hemsleyanum.

CD4+ and CD8+ T cells reduce inflammation and promote bone healing in response to titanium implants.

T cells are adaptive immune cells essential in pathogenic response, cancer, and autoimmune disorders. During the integration of biomaterials with host tissue, T cells modify the local inflammatory environment by releasing cytokines that promote inflammatory resolution following implantation. T cells are vital for the modulation of innate immune cells, recruitment and proliferation of mesenchymal stem cells (MSCs), and formation of functional tissue around the biomaterial implant. We have demonstrated that deficiency of αß T cells promotes macrophage polarization towards a pro-inflammatory phenotype and attenuates MSC recruitment and proliferation in vitro and in vivo. The goal of this study was to understand how CD4+ and CD8+ T cells, subsets of the αß T cell family, impact the inflammatory response to titanium (Ti) biomaterials. Deficiency of either CD4+ or CD8+ T cells increased the proportion of pro-inflammatory macrophages, lowered anti-inflammatory macrophages, and diminished MSC recruitment in vitro and in vivo. In addition, new bone formation at the implantation site was significantly reduced in T cell-deficient mice compared to T cell-competent mice. Deficiency of CD4+ T cells exacerbated these effects compared to CD8+ T cell deficiency. Our results show the importance of CD4+ and CD8+ T cells in modulating the inflammatory response and promoting new bone formation in response to modified Ti implants. STATEMENT OF SIGNIFICANCE: CD4+ and CD8+ T cells are essential in modulating the peri-implant microenvironment during the inflammatory response to biomaterial implantation. This study shows that deficiency of either CD4+ or CD8+ T cell subsets altered macrophage polarization and reduced MSC recruitment and proliferation at the implantation site.

Biocompatibility and Osseointegration of the Biomimetically Coated and Water-Soluble Eggshell Membrane Protein Cross-Linked Ti Alloy Screws.

Background: The surface properties of dental and orthopedic implants are directly related to their osseointegration rate. Coating and/or modifying the implant surface might reduce the time of healing. In this study, we aimed to examine the effects of a hybrid surface consisting of a brushite surface coating and cross-linked water-soluble eggshell membrane protein on the osseointegration of titanium (Ti) screws under in vivo conditions. Methods: Twenty Ti alloy screws were implanted monocortically in anteromedial regions of New Zealand rabbit tibiae. Ten screws were untreated and used as controls. The remaining 10 screws were coated with calcium phosphate and following cross-linked with ostrich eggshell membrane protein. All rabbits were sacrificed six weeks after the surgery. Peri-screw tissues were evaluated by micro-computed tomography (µ-CT), histological and histomorphometrical methods. Results: The µ-CT assessments indicated that the experimental group had significantly higher mean bone surface area (BSA) and trabeculae number (TbN) than those of the control group (p ˂ 0.05). Bone surface area (BV), trabecular separation (TbSp), trabecular thickness (TbTh), and bone mineral density (BMD) scores of the control and experimental groups were quite similar (p > 0.05). The vascularization score of the experimental group was significantly higher than the control group (4.29 vs. 0.92%). No sign of the graft-versus-host reaction was observed. Conclusion: Our findings reveal that coating Ti alloy implants with calcium phosphate cross-linked with ostrich eggshell membrane protein increases the osseointegration of Ti alloy screws by increasing the bone surface area, number of trabeculae and vascularization in the implant site.

Titanium Surfaces with a Laser-Produced Microchannel Structure Enhance Pre-Osteoblast Proliferation, Maturation, and Extracellular Mineralization In Vitro.

The clinical success of dental titanium implants is profoundly linked to implant stability and osseointegration, which comprises pre-osteoblast proliferation, osteogenic differentiation, and extracellular mineralization. Because of the bio-inert nature of titanium, surface processing using subtractive or additive methods enhances osseointegration ability but limits the benefit due to accompanying surface contamination. By contrast, laser processing methods increase the roughness of the implant surface without contamination. However, the effects of laser-mediated distinct surface structures on the osteointegration level of osteoblasts are controversial. The role of a titanium surface with a laser-mediated microchannel structure in pre-osteoblast maturation remains unclear. This study aimed to elucidate the effect of laser-produced microchannels on pre-osteoblast maturation. Pre-osteoblast human embryonic palatal mesenchymal cells were seeded on a titanium plate treated with grinding (G), sandblasting with large grit and acid etching (SLA), or laser irradiation (L) for 3-18 days. The proliferation and morphology of pre-osteoblasts were evaluated using a Trypan Blue dye exclusion test and fluorescence microscopy. The mRNA expression, protein expression, and protein secretion of osteogenic differentiation markers in pre-osteoblasts were evaluated using reverse transcriptase quantitative polymerase chain reaction, a Western blot assay, and a multiplex assay, respectively. The extracellular calcium precipitation of pre-osteoblast was measured using Alizarin red S staining. Compared to G- and SLA-treated titanium surfaces, the laser-produced microchannel surfaces enhanced pre-osteoblast proliferation, the expression/secretion of osteogenic differentiation markers, and extracellular calcium precipitation. Laser-treated titanium implants may enhance the pre-osteoblast maturation process and provide extra benefits in clinical application.

Ti2C3 MXene-based nanocomposite as an intelligent nanoplatform for efficient mild hyperthermia treatment.

Photothermal therapy (PTT) has attracted much attention due to its less invasive, controllable and highly effective nature. However, PTT also suffers from intrinsic cancer resistance mediated by cell survival pathways. These survival pathways are regulated by a variety of proteins, among which heat shock protein (HSP) triggers thermotolerance and protects tumor cells from hyperthermia-induced apoptosis. Confronted by this challenge, we propose and validate here a novel MXene-based HSP-inhibited mild photothermal platform, which significantly enhances the sensitivity of tumor cells to heat-induced stress and thus improves the PPT efficacy. The Ti3C2@Qu nanocomposites are constructed by utilizing the high photothermal conversion ability of Ti3C2 nanosheets in combination with quercetin (Qu) as an inhibitor of HSP70. Qu molecules are loaded onto the nanoplatform in a pH-sensitive controlled release manner. The acidic environment of the tumor causes the burst-release of Qu molecules, which deplete the level of heat shock protein 70 (HSP70) in tumor cells and leave the tumor cells out from the protection of the heat-resistant survival pathway in advance, thus sensitizing the hyperthermia efficacy. The nanostructure, photothermal properties, pH-responsive controlled release, synergistic photothermal ablation of tumor cells in vitro and in vivo, and hyperthermia effect on subcellular structures of the Ti3C2@Qu nanocomposites were systematically investigated.

Bi2S3/Ti3C2-TPP nano-heterostructures induced by near-infrared for photodynamic therapy combined with photothermal therapy on hypoxic tumors.

BACKGROUND: Photodynamic therapy (PDT) efficacy of bismuth sulfide (Bi2S3) semiconductor has been severely restricted by its electron-hole pairs (e--h+) separation inefficiency and oxygen (O2) deficiency in tumors, which greatly hinders reactive oxygen species (ROS) generation and further clinical application of Bi2S3 nanoparticles (NPs) in biomedicine. RESULTS: Herein, novel Bi2S3/titanium carbide (Ti3C2) two-dimensional nano-heterostructures (NHs) are designed to realize multimode PDT of synchronous O2 self-supply and ROS generation combined with highly efficient photothermal tumor elimination for hypoxic tumor therapy. Bi2S3/Ti3C2 NHs were synthesized via the in situ synthesis method starting from Ti3C2 nanosheets (NSs), a classical type of MXene nanostructure. Compared to simple Bi2S3 NPs, Bi2S3/Ti3C2 NHs significantly extend the absorption to the near-infrared (NIR) region and enhance the photocatalytic activity owing to the improved photogenerated carrier separation, where the hole on the valence band (VB) of Bi2S3 can react with water to supply O2 for the electron on the Ti3C2 NSs to generate ·O2- and ·OH through electron transfer. Furthermore, they also achieve 1O2 generation through energy transfer due to O2 self-supply. After the modification of triphenylphosphium bromide (TPP) on Bi2S3/Ti3C2 NHs, systematic in vitro and in vivo evaluations were conducted, revealing that the synergistic-therapeutic outcome of this nanoplatform enables complete eradication of the U251 tumors without recurrence by NIR laser irradiation, and it can be used for computed tomography (CT) imaging because of the strong X-ray attenuation ability. CONCLUSION: This work expands the phototherapeutic effect of Bi2S3-based nanoplatforms, providing a new strategy for hypoxic tumor theranostics.

Morphological and biomechanical characterization of long bones and peri-implant bone repair in type 2 diabetic rats treated with resveratrol.

Type 2 diabetes interferes with bone remodeling mechanisms, requiring studies to reverse this damage, and resveratrol is a polyphenol with rich properties. This study aimed to characterize the long bone morphology and peri-implant biomechanics of normoglycemic and type 2 diabetic animals treated with resveratrol. Thirty-two male Wistar rats were used and divided into normoglycemic and diabetic with or without treatment. They had the installation of implants in the tibia and treatment with oral resveratrol within 45 days. Resveratrol was responsible for weight homeostasis and decreased glycemic levels in rats with type 2 diabetes. The three-point bending testing, resveratrol showed positive effects on the biomechanics of long bones, corroborating a more resistant bone in comparison to untreated diabetics. Micro-ct revealed how bone metabolism is affected by systemic disease, decreasing bone quality. The counter-torque of normoglycemic animals showed superior osseointegration to diabetes, with no differences in the administration of the polyphenol, showing the sovereignty of the deleterious effects of the disease when there is a tissue lesion and an inflammatory picture installed. Overall, resveratrol acted positively in the etiopathogenesis of type 2 diabetes and revealed positive effects on the strength of long bones.

Nanoengineered chitosan functionalized titanium dioxide biohybrids for bacterial infections and cancer therapy.

Nanoengineered chitosan functionalized titanium dioxide biohybrids (CTiO2@NPs) were prepared with Amomum subulatum Roxb extract via one-pot green method and assessed by UV-Vis spectroscopy, XRD, SEM and EDAX analyses. As revealed by XRD pattern, the nanohybrids exhibits a rutile TiO2 crystallites around 45 nm in size. The emergence of the Ti-O-Ti bond is identified by observing a peak between 400 and 800 cm-1. A wide bandgap (4.8 eV) has been observed in CTiO2@NPs, due to the quantum confinement effects and the oxygen vacancies reveal the intriguing potential of developed nanohybrids for various applications. Surface flaws were identified by observing an emission band at 382, 437, 482, 517, and 556 nm. They also exhibit better antibacterial performances using well diffusion method against Staphylococcus aureus, Bacillus substilis, Klebsiella pneumonia, and Escherichia coli. CTiO2@NPs were discovered to have free radical scavenging activity on DPPH analysis and exhibit IC50 value as 95.80 µg/mL and standard (Vitamin C) IC50 is 87.62 µg/mL. CTiO2@NPs exhibited better anticancer properties against the osteosarcoma (MG-63) cell line. All these findings suggest that there is a forum for further useful therapeutic applications. Therefore, we claim that nano-engineered carbohydrated TiO2 phytohybrid is a promising solution for bacterial infections and bone cancer.

Apelin-13 alleviates osteoclast formation and osteolysis through Nrf2-pyroptosis pathway.

Wear particle-induced periprosthetic osteolysis is the key to aseptic loosening after artificial joint replacement. Osteoclastogenesis plays a central role in this process. Apelin-13 is a member of the adipokine family with anti-inflammatory effects. Here, we report that apelin-13 alleviates RANKL-mediated osteoclast differentiation and titanium particle-induced osteolysis in mouse calvaria. Mechanistically, apelin-13 inhibits NLRP3 inflammasome-mediated pyroptosis by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In summary, apelin-13 is expected to be a potential drug for relieving aseptic osteolysis. RESEARCH HIGHLIGHTS: This study reveals the molecular mechanism by which apelin-13 inhibits NLRP3 inflammasome activation and pyroptosis by promoting Nrf2. This study confirms that apelin-13 alleviates osteoclast activation by inhibiting pyroptosis. In vivo studies further confirmed that apelin-13 alleviated mouse skull osteolysis by inhibiting the activation of NLRP3 inflammasome.

CeO2 and Glucose Oxidase Co-Enriched Ti3C2Tx MXene for Hyperthermia-Augmented Nanocatalytic Cancer Therapy.

Foreseen as foundational in forthcoming oncology interventions are multimodal therapeutic systems. Nevertheless, the tumor microenvironment (TME), marked by heightened glucose levels, hypoxia, and scant concentrations of endogenous hydrogen peroxide could potentially impair their effectiveness. In this research, two-dimensional (2D) Ti3C2 MXene nanosheets are engineered with CeO2 nanozymes and glucose oxidase (GOD), optimizing them for TME, specifically targeting cancer therapy. Following our therapeutic design, CeO2 nanozymes, embodying both peroxidase-like and catalase-like characteristics, enable transformation of H2O2 into hydroxyl radicals for catalytic therapy while also producing oxygen to mitigate hypoxia. Concurrently, GOD metabolizes glucose, thereby augmenting H2O2 levels and disrupting the intracellular energy supply. When subjected to a near-infrared laser, 2D Ti3C2 MXene accomplishes photothermal therapy (PTT) and photodynamic therapy (PDT), additionally amplifying cascade catalytic treatment via thermal enhancement. Empirical evidence demonstrates robust tumor suppression both in vitro and in vivo by the CeO2/Ti3C2-PEG-GOD nanocomposite. Consequently, this integrated approach, which combines PTT/PDT and enzymatic catalysis, could offer a valuable blueprint for the development of advanced oncology therapies.

Probing the Mechanism of Action of Bis(phenolato) Amine (ONO Donor Set) Titanium(IV) Anticancer Agents.

The need for anticancer therapies that overcome metallodrug resistance while minimizing adverse toxicities is targeted, herein, using titanium coordination complexes. Octahedral titanium(IV) trans,mer-[Ti{R1N(CH2-2-MeO-4-R1-C6H2)2}2] [R1 = Et, allyl, n-Pr, CHO, F, CH2(morpholino), the latter from the formyl derivative; R2 = Me, Et; not all combinations] are attained from Mannich reactions of commercial 2-methoxyphenols (27-74% overall yield, 2 steps). These crystalline (four X-ray structures) Ti(IV)-complexes are active against MCF-7, HCT-116, HT-29, PANC-1, and MDA-MB-468 cancer cell lines (GI50 = 0.5-38 µM). Their activity and cancer selectivity (vs nontumor MRC-5 cells) typically exceeds that of cisplatin (up to 16-fold). Proteomic analysis (in MCF-7) supported by other studies (G2/M cell cycle arrest, ROS generation, γH2AX production, caspase activation, annexin positivity, western blot, and kinase screens in MCF-7 and HCT-116) suggest apoptosis elicited by more than one mechanism of action. Comparison of these data to the modes of action proposed for salan Ti(IV) complexes is made.

Saliva biofilm-derived outer membrane vesicles regulate biofilm formation and immune response of oral epithelial cells on titanium surfaces.

OBJECTIVES: While the significant roles of outer membrane vesicles (OMVs) from individual oral bacterial species in bacterial-host interactions are known, the involvement of saliva biofilm-derived OMVs in peri-implant disease pathogenesis remains unclear. This study aimed to investigate the effect of saliva biofilm-derived OMVs on regulating saliva biofilm formation and modulating the immune response of the epithelial cells on titanium surfaces. MATERIALS AND METHODS: Saliva derived biofilms were cultured on tissue culture plates (TCP) for 4 days using pooled saliva from four healthy donors. OMVs secreted from the TCP bound biofilm (referred to as OMVs or healthy saliva biofilm OMVs) were enriched using the size-exclusion chromatography method. We then evaluated the effects of these OMVs on the viability, metabolic activity, and the presence of oral pathogens in saliva biofilm grown on titanium discs for 24 h and 72 h. Furthermore, the impact of OMVs on the mRNA expression and inflammatory cytokines [interleukin (IL)-6, IL-1α, and monocyte chemoattractant protein-1 (MCP-1)] in human oral epithelial cells (OKF6/TERT-2) was investigated using RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Healthy saliva biofilm OMVs improved the biomass and activity of saliva biofilm cultured on the titanium surfaces, with inhibited Porphyromonas gingivalis and Fusobacterium nucleatum, and enhanced Streptococcus mutans expression. Additionally, OMVs increased pro-inflammatory cytokine IL-6 mRNA and IL-6 cytokine expression in human oral epithelial cells. However, IL-1α and MCP-1 cytokines were inhibited 24-hour post-incubation with OMVs. CONCLUSION: Healthy saliva biofilm derived OMVs regulate the activity and pathogen composition of biofilms formed on titanium, while modulating the secretion of pro-inflammation factors of oral epithelial cells grown on titanium surfaces. CLINICAL RELEVANCE: Healthy saliva biofilm OMVs may regulate the early biofilm formation on abutment surfaces and modulate epithelial cell immune response, which may alter the peri-implant niche and participate in the pathogenesis of peri-implant disease.

Titanium-based substrate modified with nanoenzyme for accelerating the repair of bone defect.

Titanium (Ti) and titanium alloy are the most common metal materials in clinical orthopedic surgery. However, in the initial stage of surgery and implantation, the production of excessive reactive oxygen species (ROS) can induce oxidative stress (OS) microenvironment. OS will further inhibit the growth of new bone, resulting in surgical failure. In this study, based on the fact that nanoscale manganese dioxide (MnO2) can show H2O2-like enzyme activity, a MnO2 nanocoating was prepared on mciro-nano structured surface of Ti substrate via a two-step method of alkaline thermal and hydrothermal treatment. The results of scanning electron microscopy (SEM), X-ray diffractometer (XRD) and X-ray photoelectron spectroscopy (XPS) showed that the nano-MnO2 coating was successfully fabricated on the surface of Ti substrate. The results of measurement of H2O2, dissolved O2 and intracellular ROS in vitro showed that the treated Ti substrate could efficiently eliminate H2O2 and reduce ROS. Furthermore, the modified Ti substrate could promote the early adhesion, proliferation and osteogenic differentiation of MSCs, which was demonstrated by experimental results of cell morphology, cell viability, alkaline phosphatase, collagen, and mineralization deposition. The results of quantitative real-time polymerase chain reaction (qRT-PCR) of MSCs adhered the modified Ti substrate showed that the expression of genes related to osteogenic differentiation significantly increased. More importantly, the modified Ti implant could eliminate ROS at the injury site, reduce OS and promote the regeneration of bone tissue, which was demonstrated via hematoxylin/eosin, Masson's trichrome and immunohistochemical staining. In conclusion, the modified Ti implant presented here had the effect of reducing OS and promoting osseointegration. Relevant research ideas and results provide new methods for the research and development of functional implants, which have potential application value in the field of orthopedics.

Thermal spray processes influencing surface chemistry and in-vitro hemocompatibility of hydroxyapatite-based orthopedic implants.

Orthopedic implants made from titanium are a popular choice in the medical field because of their remarkable strength-to-weight ratio. Nevertheless, they may not interact well with human blood, resulting in thrombosis and hemolysis. In fact, non-hemocompatibility is believed to be responsible for about 31 % of medical device failures in the US alone, requiring painful and expensive revision surgery. To address this issue, bioactive hydroxyapatite coatings are applied to Ti-6Al-4V implants using thermal spray techniques. However, the temperature used during thermal processing impacts the coating's surface properties, affecting the mechanical and biological properties. Furthermore, the effectiveness of HA coatings on titanium for orthopedic applications has not been validated by biocompatibility tests, particularly hemocompatibility. In this study, we aimed to investigate the relative efficacy of three thermal spray processes of different temperature ranges: Atmospheric plasma spray (APS) (high temperature), Flame spray (FS) (moderate temperature), and High-Velocity Oxy-Fuel spray (HVOF) (low temperature), and study their impact on coating's surface properties, affecting blood components and implant's strength. The crystallinity of the HA coating increased by 32 % with a decrease in the operating temperature (APS < FS < HVOF). HVOF coating exhibited a ~ 34 % and ~ 120 % improvement in adhesion strength and ~ 31 % and 59 % increment in hardness compared to APS and FS coating, respectively, attributed to its low porosity, low coating thickness (~55 µm), and high degree of crystallinity. The HVOF coating showcased a significant increase in non-hemolytic behavior, with hemolysis rates ~8 and ~ 11 times lower than APS and FS coatings, respectively, owing to its smooth texture and high degree of crystallinity (p < 0.05). Furthermore, the HVOF coating exhibited minimal blood clotting based on the whole blood clotting assay, again confirmed by PT and aPTT assays showing delayed clotting time, indicating its non-thrombogenic behavior. The number of platelets adhered to the three coatings showed no significant difference compared to Ti-6Al-4V. APS and FS coatings showed low platelet activation, unlike HVOF coating and titanium, which revealed round platelets, similar to the negative control. Neither titanium nor HA coatings exhibited antibacterial properties, which may be due to their high affinity for organic substances, which promotes bacterial adhesion and replication. Among the three thermal processes, HVOF coating displayed good apatite growth, non-hemolytic, and non-thrombogenicity with no platelet activation owing to its low processing temperature, high degree of crystallinity (89.7 %), hydrophilicity, smooth (~4 µm) and dense (~97 %) microstructural properties. The results demonstrated that the HVOF-HA coating presented in this work meets the hemocompatible requirements and shows promise for prospective application as an orthopedic implant. Furthermore, this study has the potential to significantly reduce the use of animals in in-vivo research and improve their welfare while also cutting costs.

Preparation of titanium dioxide nanoparticles from Solanum Tuberosum peel extract and its applications.

The present study describes a method for the preparation of green titanium dioxide (TiO2) nanoparticles from the peel of Solanum tuberosum, commonly known as potato, and the potato peel being a kitchen waste. The green synthesized TiO2 (G- TiO2) nanoparticles were characterized using UV-visible spectroscopy, dynamic light scattering, scanning electron microscopy, TEM, XRD, and FTIR spectroscopy. The photocatalytic activity of the G- TiO2 nanoparticles was also shown using the dye bromophenol blue. To explore the biocompatibility of the G- TiO2, the cell viability in normal as well as cancer cells was assessed. Further, the in vivo toxicity of the G- TiO2 nanoparticles was assessed using zebrafish embryos. The novelty of the present invention is to utilize kitchen waste for a useful purpose for the synthesis of titanium dioxide nanoparticles which is known to have UV light scavenging properties. Moreover, the potato peel is a natural antioxidant and possesses a skin-lightening effect. A combination of the potato peel extract and titanium dioxide prepared using the extract will have a combinatorial effect for protecting UV light exposure to the skin and lightening the skin colour.

GL13K-modified titanium regulates osteogenic differentiation via the NF-κB pathway.

The osteoimmune response plays a crucial regulatory role in the osseointegration of dental implants. Previous studies found the antimicrobial peptide coating (GL13K) could activate the immunomodulatory potential of macrophages (Raw 264.7) and promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). To further investigate the mechanism of interaction between immunomodulation and differentiation, a co-culture model of the representative cells (Raw 264.7 and BMSCs) was constructed to mimic the immune microenvironment. In this system, GL13K coating of titanium implant effectively inhibited the polarization of the inflammatory M1 type and promoted the polarization of the anti-inflammatory M2 type. Furthermore, the inhibited NF-κB signaling pathway and Mip-2 gene expression were found and validated by bioinformatics analysis and virus-induced gene silencing, which significantly affected the tissue repair process. It can be concluded that the GL13K coating had the potential to establish a localized immune microenvironment conducive to osteogenic differentiation through cellular interactions. Subsequent investigations would be dedicated to a thorough examination of the osseointegration effects of GL13K coating.

Photoelectrons Sequentially Regulate Antibacterial Activity and Osseointegration of Titanium Implants.

Titanium implants are widely used ; however, implantation occasionally fails due to infections during the surgery or poor osseointegration after the surgery. To solve the problem, an intelligent functional surface on titanium implant that can sequentially eradicate bacteria biofilm at the initial period and promote osseointegration at the late period of post-surgery time is designed. Such surfaces can be excited by near infrared light (NIR), with rare earth nanoparticles to upconvert the NIR light to visible range and adsorb by Au nanoparticles, supported by titanium oxide porous film on titanium implants. Under NIR irradiation, the implant converts the energy of phonon to hot electrons and lattice vibrations, while the former flows directly to the contact substance or partially reacts with the surrounding to generate reactive oxygen species, and the latter leads to the local temperature increase. The biofilm or microbes on the implant surface can be eradicated by NIR treatment in vitro and in vivo. Additionally, the surface exhibits superior biocompatibility for cell survival, adhesion, proliferation, and osteogenic differentiation, which provides the foundation for osseointegration. In vivo implantation experiments demonstrate osseointegration is also promoted. This work thus demonstrates NIR-generated electrons can sequentially eradicate biofilms and regulate the osteogenic process, providing new solutions to fabricate efficient implant surfaces.

Evaluation of nanoscale versus hybrid micro/nano surface topographies for endosseous implants.

We examined the effect of a nanoscale titanium surface topography (D) versus two hybrid micro/nanoscale topographies (B and OS) on adherent mesenchymal stem cells (MSCs) and bone marrow derived macrophages (BMMs) function in cell culture and in vivo. In the in vitro study, compared to OS and B surfaces, D surface induced earlier and greater cell spreading, and earlier and profound mRNA expression of RUNX2, Osterix and BMP2 in MSCs. D surface induced earlier and higher expression of RUNX2 and BMP2 and lower expression of inflammatory genes in implant adherent cells in vivo. Measurement of osteogenesis at implant surfaces showed greater bone-to-implant contact at D versus OS surfaces after 21 days. We explored the cell population on the D and OS implant surfaces 24 h after placement using single-cell RNA sequencing and identified distinct cell clusters including macrophages, neutrophils and B cells. D surface induced lower expression and earlier reduction of inflammatory genes expression in BMMs in vitro. BMMs on D, B and OS surfaces demonstrated a marked increase of BMP2 expression after 1 and 3 days, and this increase was significantly higher on D surface at day 3. Our data implicates a dynamic process that may be influenced by nanotopography at multiple stages of osseointegration including initial immunomodulation, recruitment of MSCs and later osteoblastic differentiation leading to bone matrix production and mineralization. The results suggest that a nanoscale topography (D) favorably modulates adherent macrophage polarization toward anti-inflammatory and regenerative phenotypes and promotes the osteoinductive phenotype of adherent mesenchymal stem cells. STATEMENT OF SIGNIFICANCE: Our manuscript contains original data developed to define effects of a novel nanotopography on the process of osseointegration at the cell and tissue level.  Few studies have compared the effects of a nanoscale surface versus the more typical hybrid micro/nano-scale surfaces used today. We have utilized single-cell RNA sequencing for the first time to identify earliest cell populations on implant surfaces in vivo. We provide data indicating that the nanoscale surface acts upon both osteoprogenitor and immune cell (macrophages) to alter the process of bone formation in a surface-specific manner. This work represents new observations regarding osseointegration and immunomodulation.

In vitro evaluation of cytotoxicity and genotoxicity of porous nickel titanium dental implants produced by metal injection molding technique.

Porous NiTi (pNiTi) is a promising biomaterial for functional long-term implantation that has been produced using various manufacturing techniques and tested for biocompatibility. pNiTi produced using a more recent technology of Metal Injection Molding (MIM) has shown better physical and mechanical properties than those produced by earlier manufacturing methods, but its biocompatibility has yet to be determined. Hence, extracts from pNiTi dental implants produced by MIM were tested for cytotoxicity and genotoxicity in this work. Its toxicity was evaluated at the cellular and in vitro levels using elution and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Short-term testing revealed that pNiTi extract was cytocompatible with L-929 fibroblast and V79-4 lung cells, with no cell lysis or reactivity observed, respectively (USP grade 0). Following exposure to varied extract concentrations, good cell viability was observed where the lowest concentration showed the highest optical density (OD) and cell viability (2.968 ± 0.117 and 94%, respectively), and the highest concentration had the least OD and cell viability (2.251 ± 0.054 and 71%, respectively). pNiTi extracts demonstrated genocompatibility in two independent assays: mutagenic potential using a bacterial reverse mutation test and a clastogenic effect on chromosomes using the micronucleus test. Similar to the negative control reactions, there was no significant increase in revertant colonies following exposure to 100% pNiTi extract with and without metabolic activation (p = .00). No DNA clastogenic activity was caused by pNiTi at varied extract concentrations as compared to the negative control when tested with and without metabolic activation (p = .00). As a result, both cytotoxic and genotoxic investigations have confirmed that pNiTi dental implants utilizing the MIM process are cytocompatible and genocompatible in the short term, according to the International Standard, ISO 10993 - Parts 3, 5, and 33.