Table 1. A descriptive summary of the findings are tabulated based on the focused question.
| # | Author year | Title | Study design | In vivo/ in vitro studies cell type | Biomaterial | Limitations | Assay used | Pathway identified |
Osteogensis/
angiogenesis |
Outcome/
Findings |
Quality of study (100) | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Material used |
Biomaterial Characteristics/
Dimensions |
|||||||||||
| 1 | (Zhang et al., 2011) China | Analysis of the cytotoxicity of differentially sized titanium dioxide nanoparticles in murine MC3T3-E1 preosteoblasts | Cell culture study | MC3T3-E1 murine preosteoblasts | Titanium oxide nanoparticles (TiO2 NPs) | 5 and 32 nm in diameter | * The cellular and molecular cross talk in bone remodeling were not identified. * The effect of TiO2NPs induced oxidative stress on the osteogenesis-angiogenesis coupling in bone remodeling were not identified. | The tetrazolium salt MTT method and lactate dehydrogenase (LDH) assay. Annexin V apoptosis detected by a flow cytometric assay. TEM analysis. Mitochondrial membrane permeability assay. RNA extraction and real-time quantitative RT-PCR analysis. | ND | Osteogenesis | TiO2 NPs induced a time- and dose dependent decrease in cell viability. There was a significant increase in lactate dehydrogenase (LDH) release, apoptosis and mitochondrial membrane permeability following short term exposure of the cells to TiO2 NPs. Compared with the 32 nm TiO2 NPs, 5 nm TiO2 NPs were more toxic. | 70 Strong Evidence |
| 2 | (El-Shenawy et al., 2012) Saudi Arabia | Oxidative stress and antioxidant responses of liver and kidney tissue after implantation of titanium or titanium oxide coated plate in rat tibiae | Cell culture study + Animal study | Wistar rats Serum | TiO2 plate Ti plare | 3.0 × 1.0 × 0.25 mm | * The cellular and molecular cross talk in bone remodeling were not identified. * The effect of TiO2 nanotubes reduced oxidative stress on the osteogenesis-angiogenesis coupling in bone remodeling were not identified. | Plasma mass spectrometer (ICP-MS). Hematology autoanalyzer Cell counter (Sysmex, model KX21N). Flame photometry. Bio-Rad protein assay reagent. Lipid peroxidation assay. Superoxide dismutase (SOD) activity assay. Reduced glutathione assay. ferric reducing/ antioxidant power (FRAP) assay. | ND | NA oxidative stress | Ti-implantation could not decrease thiobarbituric acid reactive product malondialdehyde (MDA) level. TiO2/Ti-plate did not induce elevation of MDA in liver and kidney tissues, however, some antioxidant have been changed. TiO2/Ti-plate has less effect on the redox stat of rat than Ti-plate for use as an artificial surgical implant. | 61.66 Moderate Evidence |
| 3 | (Lee et al., 2013) Korea | Bone regeneration around N-acetyl cysteine-loaded nanotube titanium dental implant in rat mandible | Cell culture study + Animal study | MC-3T3 E1 osteoblast-like cells. Sprague Dawley rats | Ti nanotubes. Ti nanotube mini screws. | 1 × 1 cm 1 mm and 6 × 6 cm 1 mm in vitro. 4.5 mm in length and a diameter of 0.85 mm were used for in vivo. | * The cellular and molecular cross talk in bone remodeling were not identified. * The effect of Ti nanotube reduced oxidative stress on the osteogenesis-angiogenesis coupling in bone remodeling were not identified. | wettability. assessment of surface hydrophobicity and hydrophilicity. Cell viability assays. Total nitric oxide (NO) analysis. ELISA. Western blot analysis. Micro-computed tomography (m-CT) analysis. (H&E) staining and immunohistochemical (IHC) staining | RANKL expression | Osteogenesis | MC-3T3-E1 cells seeded on pure Ti and nanotube Ti surfaces increased the expression of RANKL and markedly diminished the expressions of BMP-2, -7 and SPARC. Compared with NLP-Ti, NLN-Ti surfaces attenuated the level of RANKL expression and expression of antioxidants enzymes and bone formation molecules, such as BMP-2 and -7. | 86.66 Strong Evidence |
| 4 | (Pietropaoli et al., 2013) Italy | Glycation and oxidative stress in the failure of dental implants: a case series | case series | Human Study | Dental Implant | ND | * Limitation of the sample size * The molecular pathways that are involved in periimplantitis were not identified. * Implant characteristics were not mentioned. | SDS-Page Electrophoresis. Western Blotting. Colorimetric assay for ThioBarbituric Acid Reactive Substances (TBARS). | ND | NA oxidative stress | The chronic periodontal disease group showed higher oxidative stress than periimplantitis and healthy groups. Periimplantitis group compared to the healthy one had higher oxidative stress levels | 65 Moderate Evidence |
| 5 | (Xie et al., 2014) ) China | Study on potential toxic of titanium oxide nanoparticles on osteoblasts | Cell culture study | Osteoblast cells | Titanium oxide nanoparticles (TiO2-NPs) | less than 25 nm. | * The cellular and molecular cross talk in bone remodeling were not identified. * The effect of TiO2NPs induced oxidative stress on the osteogenesis-angiogenesis coupling in bone remodeling were not identified. | MTS reagent kit for cytoactive detection. LDH reagent kit for cytotoxicity detection. ROS detection reagent kit. RIPA cell lysis. Transmission electron microscopy (TEM). Zetasizer particle size analyzer Malvern Instrument, Ultrasonic oscillation instrument. Inverted phase contrast microscope. | ND | Osteogenesis | TiO2-NPs can cause the decrease of the survival rate of the osteoblast and increase of the content of the LDH released by the cell, and with dosage dependency effect | 71.66 Strong Evidence |
| 6 | (Niska et al., 2015) Poland | Titanium dioxide nanoparticles enhance production of superoxide anion and alter the antioxidant system in human osteoblast cells | Cell culture study | hFOB 1.19 human osteoblast cells | TiO2NPs | TiO2NPs size 5–15 nm |
* The cellular and molecular cross talk in bone remodeling were not identified. * The effect of TiO2NPs induced oxidative stress on the osteogenesis-angiogenesis coupling in bone remodeling were not identified. | Water-soluble tetrazolium salt (WST) 1 assay. Mitochondrial activity assay. Transmission electron microscope (TEM) analysis. Lactate dehydrogenase (LDH) assay. Alkaline phosphatase (ALP) activity. Flow cytometry. Total antioxidant capacity. | SIR3 ROS pathway | Osteogenesis | Significant positive correlation between SIR3 and MnSOD at the protein level and a significant negative correlation between decreased SIR3 protein level and increased O2•– level | 83.33 Strong Evidence |
| 7 | (Mariarosaria et al., 2017) Italy | Oxidative Stress Evaluation During Perimplantar Bone Resorption in Immediate Post-Extractive Implant | RCT | Human study | Dental Implant | V3 MIS® implant | * The molecular pathways that are involved in perimplantar bone resorption were not identified. * The cellular and molecular cross talk in bone remodeling were not identified. * The effect of biomaterial induced oxidative stress on the osteogenesis-angiogenesis coupling in bone remodeling were not identified. | Thiobarbituric acid reactive substances (TBARs). Nitrite assay. Immunoenzymatic assay for interleukin. Cicloxygenase-2 (COX-2) immunoprecipitation. | ND | Osteoclastogenesis | An increase, during implant integration between the first and third week, of both oxidative stress markers and cyclooxygenase-2 expression. At sixteen week the parameters evaluated returned to basal values. | 63.33 Moderate Evidence |
| 8 | (Borys et al., 2018) Poland | Exposure to Ti4Al4V Titanium Alloy Leads to Redox Abnormalities, Oxidative Stress, and Oxidative Damage in Patients Treated for Mandible Fractures | RCT | Human study | Ti4Al4V Titanium alloy | Gray-pigmented periosteum adhered to the titanium miniplates | Only the most commonly used biomarkers of oxidative stress; therefore were evaluated, the assessment of other parameters may lead to different observations and conclusions. | Antioxidant Assays Total antioxidant capacity (TAC). Oxidative Damage Determination Assay | ND | Osteoclastogenesis | Increased activity/concentration of antioxidants both in the mandibular periosteum and plasma/erythrocytes of patients with titanium mandibular fixations. | 77.66 Strong Evidence |
| 9 | (Hu et al., 2018) China | Angiogenesis impairment by the NADPH oxidase-triggered oxidative stress at the bone-implant interface: Critical mechanisms and therapeutic targets for implant failure under hyperglycemic conditions in diabetes | Cell culture study + Animal study | HUVEC | Ti4Al4V Titanium alloy | (1) Circular disks (2) Sscrews. Circular disks were used in experiments in vitro and screws in study in vivo. | * The cellular and molecular cross talk in bone remodeling were not identified. * The effect of biomaterial induced oxidative stress on the osteogenesis-angiogenesis coupling in bone remodeling were not identified. | Immunofluorescent histochemistry. Real-time quantitative PCR (qPCR). Micro-CT analysis. MTT Assay. Matrigel tube-formation assay. Wound-healing assay. ROS assay. Western blot analysis. Immunohistochemical evaluation. ATP assay. Analysis of mitochondrial membrane potential (MMP). | NOX, APO, Nog and Bmp-2 | osteogenesis, angiogensis and adipogenesis | The advanced glycation end products (AGEs)-related and NOX-triggered cellular oxidative stress leads to vascular endothelial cell (VEC) dysfunction and angiogenesis impairment at the bone-implant interface (BII), which plays a critical role in the compromised implant osteointegration under diabetic conditions. | 90 Strong Evidence |
| 10 | (Yu et al., 2018) China | Osteogenesis potential of different titania nanotubes in oxidative stress microenvironment | Cell culture study | Calvaria osteoblasts | Titanium foils | TNT30, TNT70 and TNT110 | * The cellular and molecular cross talk in bone remodeling were not identified. * The effect of TiO2 nantube reduced oxidative stress on the osteogenesis-angiogenesis coupling in bone remodeling were not identified. | Scanning electron microscopy. Atomic force microscopy. X-ray diffraction. Video-based optical system. MTT. BCA assay kit. confocal laser scanning microscopy. quantitative-polymerase chain reaction (q-PCR). | Wnt signals | Osteogenesis | Large nanotubes displayed strong capacities to improve cell adhesion, survival and differentiation of osteoblasts after H2O2 treatment. | 86.66 Strong Evidence |
| 11 | (Shen et al., 2019) China | Titania nanotubes promote osteogenesis via mediating crosstalk between macrophages and MSCs under oxidative stress | Cell culture study | Mesenchymal stem cells (MSCs). RAW264.7 cells. | Titanium foils. Titanium nantubes | TNT30, TNT70 and TNT110 | Should be implemented in vivo and humans. | Confocal laser scanning microscope. Cell viability assay. Nitrous oxide (NO) assay ELISA. real-time quantitative-polymerase chain reaction (q-PCR) technique. Western Blot (WB) technique | integrin/FAK-mediated MAPK and NFκB signals | Osteogenesis | Large nanotubes (110 nm) could recruit more MSCs to the injury site than Ti and TNT30 substrates by increasing the chemokine expressions of RAW264.7 cells under OS. | 99.33 Strong Evidence |
| 12 | (Mijiritsky et al., 2019) Italy | Presence of ROS in inflammatory environment of peri-implantitis tissue: in vitro and in vivo human evidence | Cross-sectional study | Human study | Dental Implant | ND | * Limitation of the sample size * The molecular pathways that are involved in periimplantitis were not identified. * Implant characterestics were not mentioned. | Immunohistochemistry and Histomorpholgical Analyses. Immunofluorescence Staining. Transmission Electron Microscopy (TEM). RNeasy Mini Kit. | WNT, HEDGEHOG, and FOXO | Osteogenesis and adipogenesis | Osteogenesis down expressed in peri-implantitis and up regulated in the control. | 78.33 Strong Evidence |
| 13 | (Yang et al., 2020) China | TiO2 Nanotubes Alleviate Diabetes-Induced Osteogenetic Inhibition | Cell culture study + Animal study | pre-osteoblastic cell line, MC3T3-E1 Sprague–Dawley (SD) rats. | In vitro; Ti discs divided into 3 groups –mechanically polished (MP group), sandblasted and acidetched (SLA group), and oxidized TiO2 nanotubes (TNT group). In vivo; pure Ti implants | In vitro; dimensions: 10.0 × 10.0 × 0.3 mm4 or 20.0 × 20.0 × 0.3 mm4. In vivo; a diameter and length of 2 and 4 mm. | * The cellular and molecular cross talk in bone remodeling were not identified. * The effect of TiO2 nantube reduced oxidative stress on the osteogenesis-angiogenesis coupling in bone remodeling were not identified. | CCK-8 assay. Alkaline phosphatase (ALP) assay. osteopontin (OPN) assay. Western blot test. Alizarin Red staining. Flow cytometry. Superoxide Dismutase (SOD) activity sssay. micro-CT scan. | ND | Osteogenesis | High-glucose conditions inhibited ALP and OPN expressions on different modified Ti surfaces, TNT surface could alleviate the inhibition of ALP and OPN expressions under high-glucose conditions. High-glucose conditions inhibited osteogenesis on different modified Ti surfaces, The TNT surface could alleviate the inhibition of mineralization when compared with the SLA surface under high glucose conditions. | 88.33 Strong Evidence |
| 14 | (Huang et al., 2021) China | Bioadaptation of implants to in vitro and in vivo oxidative stress pathological conditions via nanotopography-induced FoxO1 signaling pathways to enhance Osteoimmunal regeneration | Cell culture study + Animal study | 1) BMSCs 2) RAW264.7 | TiO2 nanotube (TNT). | 1) Pure Ti foils 2) Cylinder- shaped (disck)pure Ti implants. | * The cellular and molecular cross talk in bone remodeling were not identified. * The effect of biomaterial induced oxidative stress on the osteogenesis-angiogenesis coupling in bone remodeling were not identified. | Scanning electron microscopy. Laser scanning confocal microscope profilometer. Contact angle analyzer. | FoxO1-induced oxidation resistance and anti-inflammatory osteoimmunity. | Osteogenesis | Nanoscale TNT coatings on titanium implants exhibited superior osteogenesis and osseointegration compared with microscale SLA surfaces. | 86.66 Strong Evidence |