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International Journal of Environmental... May 2022Titanium dioxide, first manufactured a century ago, is significant in industry due to its chemical inertness, low cost, and availability. The white mineral has a wide... (Review)
Review
Titanium dioxide, first manufactured a century ago, is significant in industry due to its chemical inertness, low cost, and availability. The white mineral has a wide range of applications in photocatalysis, in the pharmaceutical industry, and in food processing sectors. Its practical uses stem from its dual feature to act as both a semiconductor and light scatterer. Optical performance is therefore of relevance in understanding how titanium dioxide impacts these industries. Recent breakthroughs are summarised herein, focusing on whether restructuring the surface properties of titanium dioxide either enhances or inhibits its reactivity, depending on the required application. Its recent exposure as a potential carcinogen to humans has been linked to controversies around titanium dioxide's toxicity; this is discussed by illustrating discrepancies between experimental protocols of toxicity assays and their results. In all, it is important to review the latest achievements in fast-growing industries where titanium dioxide prevails, while keeping in mind insights into its disputed toxicity.
Topics: Humans; Titanium
PubMed: 35565075
DOI: 10.3390/ijerph19095681 -
IARC Monographs on the Evaluation of... 1989
Review
Topics: Animals; Carcinogens; Chemical Phenomena; Chemistry; Humans; Risk Factors; Titanium
PubMed: 2699903
DOI: No ID Found -
Journal of Trace Elements in Medicine... May 2019Joint replacement implants are usually manufactured from cobalt-chromium or titanium alloys. After the device is implanted, wear and corrosion generate metal particles... (Review)
Review
BACKGROUND
Joint replacement implants are usually manufactured from cobalt-chromium or titanium alloys. After the device is implanted, wear and corrosion generate metal particles and ions, which are released into local tissue and blood. The metal debris can cause a range of adverse local and systemic effects in patients.
RESEARCH PROBLEM
In the case of cobalt and chromium, a blood level exceeding 7 μg L indicates potential for local toxicity, and a failing implant. It has been repeatedly suggested in the literature that measurement of titanium could also be used to assess implant function. Despite an increasing interest in this biomarker, and growing use of titanium in orthopaedics, it is unclear what blood concentrations should raise concerns. This is partly due to the technical challenges involved in the measurement of titanium in biological samples.
AIM
This Review summarises blood/serum titanium levels associated with well-functioning and malfunctioning prostheses, so that the prospects of using titanium measurements to gain insights into implant performance can be evaluated.
CONCLUSION
Due to inter-laboratory analytical differences, reliable conclusions regarding "normal" and "abnormal" titanium levels in patients with orthopaedic implants are difficult to draw. Diagnosis of symptomatic patients should be based on radiographic evidence combined with blood/serum metal levels.
Topics: Biomarkers; Humans; Joint Prosthesis; Materials Testing; Titanium
PubMed: 30910194
DOI: 10.1016/j.jtemb.2019.02.013 -
Current Topics in Medicinal Chemistry 2023Titanocene dichloride and budotitane have opened a new chapter in medicinal chemistry of titanium complexes being novel non-platinum antitumor metallic agents. Numerous... (Review)
Review
Titanocene dichloride and budotitane have opened a new chapter in medicinal chemistry of titanium complexes being novel non-platinum antitumor metallic agents. Numerous efforts have led to the discovery of the diamino -phenolato titanium complexes. Among which, the [ONNO] and [ONON] type ligands namely Salan, Salen and Salalen coordinated titanium alkoxyl complexes have demonstrated significantly enhanced aqueous stability, their and antitumor efficacy, mechanism of action, structure-activity relationships and combined tumor therapy have been intensively investigated. Replacement of the labile alkoxyls with a second chelator resulted in structural rigid titanium complexes, which showed exceedingly good aqueous stability and potent antitumor activity both and . The unique ligand system successfully allowed the access of isotopic [Ti]Titanium complexes, post-synthetic modification, facile synthetic protocols and antitumor congeneric zirconium and hafnium complexes. This review presents recent research progress in the field of antitumor group 4 metal complexes stabilized with phenolato ligands; especially their structure-activity relationships are summarized.
Topics: Humans; Titanium; Ligands; Neoplasms; Organometallic Compounds; Structure-Activity Relationship; Antineoplastic Agents; Coordination Complexes
PubMed: 37151173
DOI: 10.2174/1568026623666230505104626 -
Metal Ions in Life Sciences Feb 2018Titanium(IV) coordination complexes represent attractive alternatives to platinumbased anticancer drugs. The advantage of the titanium metal lies in its low toxicity,... (Review)
Review
Titanium(IV) coordination complexes represent attractive alternatives to platinumbased anticancer drugs. The advantage of the titanium metal lies in its low toxicity, and the hydrolysis of titanium(IV) coordination complexes in biological water-based environment to the safe and inert titanium dioxide is an enormous benefit. On the other hand, the rapid hydrolysis of titanium(IV) complexes in biological environment and their rich aquatic chemistry hampered the exploration and the development of effective compounds. Titanium(IV) complexes were the first to enter clinical trials for cancer treatment following the success of platinum-based chemotherapy, with the pioneering compounds titanocene dichloride and budotitane. Despite the high efficacy and low toxicity observed in vivo, the compounds failed the trials due to insufficient efficacy to toxicity ratio and formulation complications. The rapid hydrolysis of the complexes led to formation of multiple undefined aggregates and difficulties in isolating and identifying the particular active species and its precise cellular target. Numerous derivatives with different labile ligands or substitutions on the inert ones contributed to improve the complex anticancer features, and the best ones were comparable with, and occasionally better than cisplatin. Hydrolytic stability was improved in some cases but remained challenging. The following generation of phenolato-based complexes that came three decades later exhibited high activity and markedly improved stability, where no dissociation was observed for weeks in biological solutions. Complexes of no labile ligands whatsoever that remain intact in solution demonstrated in vitro and in vivo efficacy, with no signs of toxicity to the treated animals. Mechanistic insights gained for the different complexes analyzed include, among others, possible interaction with DNA and induction of apoptosis. Such complexes are highly promising for future exploration and clinical development.
Topics: Animals; Antineoplastic Agents; Apoptosis; Coordination Complexes; DNA Damage; Drug Design; Humans; Models, Molecular; Molecular Structure; Neoplasms; Organometallic Compounds; Structure-Activity Relationship; Titanium
PubMed: 29394027
DOI: 10.1515/9783110470734-014 -
Nanotheranostics 2021Titanium is considered to be a metal material with the best biological safety. Studies have proved that the titanium implanted in the bone continuously releases titanium... (Review)
Review
Titanium is considered to be a metal material with the best biological safety. Studies have proved that the titanium implanted in the bone continuously releases titanium particles (Ti particles), significantly increasing the total titanium content in human body. Generally, Ti particles are released slowly without causing a systemic immune response. However, the continuous increased local concentration may result in damage to the intraepithelial homeostasis, aggravation of inflammatory reaction in the surrounding tissues, bone resorption and implant detachment. They also migrate with blood flow and aggregate in the distal organ. The release of Ti particles is affected by the score of the implant surface structure, microenvironment wear and corrosion, medical operation wear, and so on, but the specific mechanism is not clear. Thus, it difficult to prevent the release completely. This paper reviews the causes of the Ti particles formation, the damage to the surrounding tissue, and its mechanism, in particular, methods for reducing the release and toxicity of the Ti particles.
Topics: Corrosion; Dental Implants; Humans; Inflammation; Surface Properties; Titanium
PubMed: 33732603
DOI: 10.7150/ntno.56401 -
ACS Biomaterials Science & Engineering Aug 2023Dental implants have become the mainstream strategy for oral restoration, and implant materials are the most important research hot spot in this field. So far, Ti... (Review)
Review
Dental implants have become the mainstream strategy for oral restoration, and implant materials are the most important research hot spot in this field. So far, Ti implants dominate all kinds of implants. The surface properties of the Ti implant play decisive roles in osseointegration and antibacterial performance. Surface modifications can significantly change the surface micro/nanotopography and composition of Ti implants, which will effectively improve their hydrophilicity, mechanical properties, osseointegration performance, antibacterial performance, etc. These optimizations will thus improve implant success and service life. In this paper, the latest surface modification techniques of Ti dental implants are systematically and comprehensively reviewed. The various biomedical functionalities of surface modifications are discussed in-depth. Finally, a profound comment on the challenges and opportunities of this frontier is proposed, and the most promising directions for the future were explored.
Topics: Titanium; Dental Implants; Osseointegration; Surface Properties; Anti-Bacterial Agents
PubMed: 37523241
DOI: 10.1021/acsbiomaterials.3c00183 -
Journal of Biomedical Materials... Jul 2022Apart from osseointegration, the stability and long-term survival of percutaneous titanium implants is also strongly dependent on a qualitative soft-tissue integration... (Review)
Review
Apart from osseointegration, the stability and long-term survival of percutaneous titanium implants is also strongly dependent on a qualitative soft-tissue integration in the transcutaneous region. A firm connective tissue seal is needed to minimize soft-tissue dehiscence and epithelial downgrowth. It is well-known that the implant surface plays a key role in controlling the biological response of the surrounding keratinized tissue and several coating systems have been suggested to enhance the soft-tissue cell interactions. Although some promising results have been obtained in vitro, their clinical significance can be debated. Therefore, the purpose of this systematic review is to gain more insight into the effect of such coatings on the interface formed with keratinized soft-tissue in vivo. A comprehensive search was undertaken in March 2021. Relevant electronic databases were consulted to identify appropriate studies using a set of search strings. In total, 12 out of 4971 publications were included in this review. The reported coating systems were assigned to several subgroups according to their characteristics: metallic, ceramic and composite. Notwithstanding the differences in study characteristics (animal model, implantation period, reported outcomes), it was noticed that several coatings improve the soft-tissue integration as compared to pristine titanium. Porous titanium coatings having only limited pore sizes (<250 μm) do not support dermal fibroblast tissue attachment. Yet, larger pores (>700 μm) allow extensive vascularized soft-tissue infiltration, thereby supporting cell attachment. Nanostructured ceramic coatings are found to reduce the inflammatory response in favor of the formation of cell adhesive structures, that is, hemidesmosomes. Biomolecule coatings seem of particular interest to stimulate the soft-tissue behavior provided that a durable fixation to the implant surface can be ensured. In this respect, fibroblast growth factor-2 entrapped in a biomimetic apatite coating instigates a close to natural soft-tissue attachment with epidermal collagen fibers attaching almost perpendicular to the implant surface. However, several studies had limitations with respect to coating characterization and detailed soft-tissue analysis, small sample size and short implantation periods. To date, robust and long-term in vivo studies are still lacking. Further investigation is required before a clear consensus on the optimal coating system allowing enhancing the soft-tissue seal around percutaneous titanium implants can be reached.
Topics: Animals; Coated Materials, Biocompatible; Osseointegration; Porosity; Prostheses and Implants; Surface Properties; Titanium
PubMed: 35103386
DOI: 10.1002/jbm.b.35025 -
Materials Science & Engineering. C,... Sep 2019Variety of implant materials have been employed in various disciplines of medical science depending on the requirement of a particular application. Metals, alloys,... (Review)
Review
Variety of implant materials have been employed in various disciplines of medical science depending on the requirement of a particular application. Metals, alloys, ceramics, and polymers are the commonly used biomaterials. The main focus of this study is to review the various structural and microstructural properties of titanium and titanium based alloys used as orthopaedic implants. Orthopaedic implants need to possess certain important qualities to ensure their safe and effective use. These properties like the biocompatibility, relevant mechanical properties, high corrosion and wear resistance and osseointegration are summarized in this review. Various attempts to improve upon these properties like different processing routes, surface modifications have also been inculcated in the paper to provide an insight into the extent of research and effort that has been put into developing a highly superior titanium orthopaedic implant.
Topics: Alloys; Animals; Biocompatible Materials; Biomechanical Phenomena; Humans; Orthopedics; Titanium
PubMed: 31147056
DOI: 10.1016/j.msec.2019.04.064 -
Regulatory Toxicology and Pharmacology... Dec 2022Titanium dioxide is a ubiquitous white material found in a diverse range of products from foods to sunscreens, as a pigment and thickener, amongst other uses. Titanium... (Review)
Review
Titanium dioxide is a ubiquitous white material found in a diverse range of products from foods to sunscreens, as a pigment and thickener, amongst other uses. Titanium dioxide has been considered no longer safe for use in foods (nano and microparticles of E171) by the European Food Safety Authority (EFSA) due to concerns over genotoxicity. There are however, conflicting opinions regarding the safety of Titanium dioxide. In an attempt to clarify the situation, a comprehensive weight of evidence (WoE) assessment of the genotoxicity of titanium dioxide based on the available data was performed. A total of 192 datasets for endpoints and test systems considered the most relevant for identifying mutagenic and carcinogenic potential were reviewed and discussed for both reliability and relevance (by weight of evidence) and in the context of whether the physico-chemical properties of the particles had been characterised. The view of an independent panel of experts was that, of the 192 datasets identified, only 34 met the reliability and quality criteria for being most relevant in the evaluation of genotoxicity. Of these, 10 were positive (i.e. reported evidence that titanium dioxide was genotoxic), all of which were from studies of DNA strand breakage (comet assay) or chromosome damage (micronucleus or chromosome aberration assays). All the positive findings were associated with high cytotoxicity, oxidative stress, inflammation, apoptosis, necrosis, or combinations of these. Considering that DNA and chromosome breakage can be secondary to physiological stress, it is highly likely that the observed genotoxic effects of titanium dioxide, including those with nanoparticles, are secondary to physiological stress. Consistent with this finding, there were no positive results from the in vitro and in vivo gene mutation studies evaluated, although it should be noted that to definitively conclude a lack of mutagenicity, more robust in vitro and in vivo gene mutation studies would be useful. Existing evidence does not therefore support a direct DNA damaging mechanism for titanium dioxide (nano and other forms).
Topics: Reproducibility of Results; Metal Nanoparticles; Titanium; Comet Assay; DNA Damage; Mutagens; DNA
PubMed: 36228836
DOI: 10.1016/j.yrtph.2022.105263