Titanium Literature Review

Biocompatibility Literature
Review
Titanium
30 July 2021
> TABLE OF CONTENTS
1. Objective ........................................................................................................................................................................................ 3
2. Biocompatibility Literature Review Summary .................................................................................................................. 3
3. Literature Search Protocol ..................................................................................................................................................... 7
4. Literature Search Results ........................................................................................................................................................ 9
5. Critical Evaluation of the Literature ..................................................................................................................................... 9
6. Biocompatibility Literature Review Conclusions ............................................................................................................ 15
7. References .................................................................................................................................................................................. 15
8. Annex X ....................................................................................................................................................................................... 16
Biocompatibility Literature Review 2/39

https://coloplastmigration-my.sharepoint.com/personal/usesny_coloplast_com/Documents/Notes/Titanium/Titanium Literature Review.docx
© 2021. All rights reserved Coloplast A/S
1. Objective
The objective of the literature review is to compile relevant biocompatibility data, favorable or unfavorable,
from peer-reviewed literature to assess the safety and performance of titanium used in implantable medical
devices.
2. Biocompatibility Literature Review Summary
Promisel once stated, “Never has there been, as in the case of titanium, the concentration of scientific and
technical devotion to a single metal . . . never has metal, normally considered so mundane, been so
extravagantly described as the wonder metal and the metal of promise [1].”
Titanium is high strength, tough, durable, corrosion resist, and highly biocompatible [2-4] as well as having
excellent mechanical strength and chemical stability. The material is highly biocompatibility due to its low-
toxicity and low rate of ion release from its surface [5].
Furthermore, metallic titanium spontaneously oxidizes to titanium dioxide in air or water and forms a
protective surface layer to prevent further oxidation, acting as a protective film. Titanium dioxide, 𝑇𝑖𝑂2 , is
found in paints, whitening agents, sunscreens, and skin care products. Titanium is also used in the industrial
field such as the metallurgic, pharmaceutical, and food industries [6, 7].
A study of films was employed in Heakal & Shehata et. al. [8]. Describing the passive films on titanium and its
alloys that allow them to excellently satisfy their biocompatibility because the films are characterized by their
spontaneous formation, adherence, self-heating, and stability. This work specifically looks at electrochemical
behavior of the native surface oxide layers on titanium in buffer solutions of different pH. Authors find the
oxide films grown spontaneously in borate buffer solutions on titanium are more stable than the ones grown
on its alloy. In addition, polarization resistance of titanium increases with increasing pH.
This metal is most prominently used in the medical industry by use in orthopedic and dental implants [2, 5, 6,
9-11]. Widespread use in these applications is because titanium its osseointegration, the formation of a strong
connection between the implant surface and the surrounding host bone [5, 11].
The metals historical use has been long documented with the first surgical experimentation being in the
1940s. Titanium was reported to be well tolerated. In 1951, a new study displayed good tissue tolerance in
rabbits [1, 12].
Pure titanium is a highly attractive biomaterial because it is inherently highly biocompatible. Commercially
pure titanium has high resistance and tissue tolerance; however, the material has a much lower strength and
unfavorable wear properties [12].
Thus, an alloy was developed from the pure titanium to create a material with better mechanical properties.
The alloy, Ti-6Al-V, is also used in medical application. However, this alloy produces concerns with toxic
elements such as vanadium and aluminum [1, 3].
Numerous studies confirmed the repeated statement of biocompatibility of titanium.
To begin, Moller et. al. [9] investigates titanium compared to zirconium dioxide implants with respect to their
biocompatibility in cell cultures. Osseointegration in adult domestic pigs was also studied in vivo. One zirconium
implant and five different titanium implants were studied. Results showed after incubation with the eluates, all

samples showed cell viability. Lactate dehydrogenase tests showed high cytotoxic effect in one titanium implant
at the 10 minute and 1 hour eluate but not in the 24-hour eluate. An MTT-test showed high activity with the
eluate from all implants. SEM examination displayed that the cells cultivated on the implant surface had good
contact in all implants. All animals that participated in the tests showed normal eating behavior after surgery
nor were there any signs of infection. Microradiographically and histologically there was no connective tissue
sheath observed on the implants. After 12 weeks it was found that the tissue was re-established as lamellar
bone in the contact zone of all implants.
Further, Goodman et. al. [13] aim to form a qualitative and quantitative histological analysis of the response of
bone to two commonly used orthopedic materials in two different physical forms. A group of 7 rabbits received
commercially pure titanium that was atraumatically wound into a helical shape then implanted into the
proximal tibia through a 6mm drill hole. A second group of 7 rabbits received commercially pure titanium
particles. Results showed that the titanium wire implants were surrounded by a variable, hypocellular fibrous
tissue layer. Particulate implants of titanium displayed gross clumping of the implant. In addition, particles were
separated from the main implant with metallic particles present within the cells. Foreign body reaction and
inflammatory cells were not present. Overall, this study finds that bulk and particulate forms of titanium in an
intraosseous location display incomplete fibrous encapsulation in a background of normal bone marrow.
Foreign body and inflammatory responses were not detected.
Another bone study was conducted in sheep. Sirak et. al. [14] assess the bone ingrowth into porous titanium
granules used for maxillary sinus augmentation in the sheep maxillary sinus augmentation model. Twelve sheep
were used in this study. The sheep were injected with infiltration anesthesia then a layer-by-layer dissection of
skin and muscle fascia offered proper access to the experimental area. Histopathological photomicrographs
revealed that at 30 days the titanium granules were overgrown and integrated in connective tissue fibers. The
rough surface as well as the high porosity of the titanium granules promoted active migration of fibroblasts in
addition to contributing to an efficient vascularization. Monocytes, macrophages and connective tissue
fibroblasts accumulated at the titanium granules sites. No inflammatory response was observed, and high
magnification displayed the ingrowth. Further, the histological observation at 90 days showed trabecular bone
growth indicating the titanium granules act as an osteoconductive scaffold when placed in bone marrow. At 3
months post implantation, newly formed bone of the defect could have been easily seen titanium granules well
incorporated into the bone matrix. Overall, the author cite that porous titanium granules are biocompatible
with bone tissue in the large animal model.
Meng et. al. [2] studies the effect of titanium particles on rat bone marrow stem cells in vitro. An assay was
performed to evaluate the effect of titanium particles on bone marrow mesenchymal stem cells (BMSCs)
viability. Significant does dependence on the decrease of cells was observed. Viability of 48 hours with titanium
particles was less than 24 hours. Therefore, a dose and time dependence were observed for BMSCs viability.
Overall, authors say these findings support the initial hypothesis that titanium particles had a cytotoxicity on
BMSCs in vitro with decrease viability and proliferation. These results could be partly due to the phagocytosis
of titanium particles and the damage of cell skeleton protein.
Furthermore, Thewes et. al. [15] studies the comparison of the number of total cells as well as different cell
subgroups and characterize the cells of perivascular infiltration in tissue adjacent to steel and titanium implants.
Results found no difference between steel and titanium implants regarding the perivascular cell infiltration in
the adjacent tissue. In conclusion, authors say it is better to remove steel implants when clinical complications
arise after osteosynthesis and after bone-healing begins in order to prevent and allergic reaction. For titanium,
authors find it is best to remain in situ.

Thomas et. al. [6] finds that released titanium may be detected in the tissues surrounding joint replacement
and lymph nodes in association with titanium screws or mini plats. In the case of dental implants, titanium is
encounters in tissues that lie adjacent to these dental implants. Overall, authors conclude that little is known
about the immune mechanisms that lead to well-tolerated titanium dental implants. Their results display that
adaptive mechanisms my exist, therefore, future studies will show factors and cell populations add to this
protective tolerance.
Szuhanek et. al. [16] further assess the biosafety of titanium. Their study looks at the biosecurity of one stainless
steel implant and two titanium-based implants by means of extraction in terms of cell morphological aspects,
cell viability, and cytotoxicity. The in vitro model was used by employing primary human gingival fibroblasts
(HGFs) cells. P3 was identified as a titanium implant. Results on the SEM analysis showed P3 has a
microstructure with a porous surface, with elevations and depressions. HGF cells did not show significant
changes with P3 compared to control cells in 72 hours and the viability of HGF cells when exposed to P3 was
98.37%. Cytotoxic effects were not significant in P3. Overall, the authors conclude the titanium implants
investigated in this study did not show cytotoxicity of HGF cell population and toxicological data show no
toxicity. These effects demonstrate a biosafe profile.
Muliple studies have used commercially pure titanium as a baseline for a novel material. For example, Kunert-
Keil et. al. [17] completed an in vitro study in order to evaluate the biocompatibility of a novel zirconium implant
surface in comparison to both commercially available zirconium and titanium implants. Results displayed that
the titanium implants had a higher surface roughness and heterogeneity than the new ceramic implants. In
addition, no significant difference in the number of dead cells among all implants. The rough surface of the
titanium implant has an impact on its ability to anchor to bone. Serra et. al. [11] explored a novel titanium. Then
compares the novel titanium to the conventional cpTi. The study processes nanostructured titanium then
mechanically compares novel titanium, cpTi, and Ti-6Al-4V, and assesses surface morphology and the fracture
surface characteristics. Results indicate that cpTi is commonly used in mini implants, however, the small size
results in numerous fractures. In addition, the biocompatibility of cpTi is largely due to the oxide film formed on
its surface, this layer is composed of 𝑇𝑖𝑂2 . In conclusion, the study finds the novel titanium encompasses the
biocompatibility cpTi mini implants and it is suggested that the novel titanium can be used as a base in
orthopedic implants.
Grenade et. al. [18] says that biocompatibility of implant materials with soft tissues constitutes a critical
parameter. More recently, advancements have been made in computer aided design and computer aided
manufacturing (CAD-CAM), introducing composite materials in addition to alloys, mainly titanium and ceramic
materials. This study firstly looks at biocompatibility of PICNs in comparison to metallic and ceramic materials
used for dental implant prostheses while assessing HGK attachment, proliferation and spreading. Secondly the
study correlates results with PICN UDMA release and indirect cytotoxicity. In conclusion the results display the
current excellent behavior of presently used materials in implant prosthodontics such as titanium. Authors say
titanium and zirconia are considered the gold standard materials in terms of gingival cell behavior.
Additionally, many investigations into the best surface topography of titanium have been conducted and
recorded.
To begin, Lu et. al. [10] investigate suitability of a nano-grained surface layer on a commercially pure titanium
sheet. Surface characteristics, biocompatibility, and in vitro corrosion behavior were investigated and
compared to coarse-grained substrate. Results show a fantastic combination of in vitro biological and anti-
corrosion and biocompatibility properties were achieved by the nano-grained surface layer on pure titanium.
Kubacka et. al. [3] also looks into grain refined surfaces. Impact of grain refinement on cellular response and
protein adsorption behavior on commercially pure (CP) titanium (Ti), CP Ti subject to hydrostatic extrusion 6

times (Ti6) and 10 times (T10) is studied. Results find similar levels of cell viability were found for the CP Ti and
Ti6 for all incubation periods. Overall, the research shows CP Ti, Ti6, and Ti10 have similar levels of
biocompatibility.
Further studies describe various ways the surface of titanium can be prepared.
Gardin et. al. [5] aims to investigate influence of grit- blasted and acid- etched titanium implants surface on the
biological response of human mesenchymal stem cells (MSCs) using in vitro tests. Results show no mutagenic
activity, and the hemolysis index was less than 2% meaning that there was an absence of any hemolytic activity.
Biocompatibility was evaluated by cultivating adipose tissue onto the surfaces of titanium for up to 30 days. A
MTT assat showed that the cells were able to adhere and proliferate on the titanium, no chromosomal
alterations are present in the adipose tissue seeded onto the titanium for 30 days, and the expression of some
osteoblast markers in adipose tissue seeded onto titanium dental implants is higher when compared to the
control. To conclude, the results find that titanium implants are not mutagenic, do not cause hemolysis, their
surfaces are biocompatible and non-toxic when seeded with adipose tissue.
Jobin et. al. [19] aims to compare electropolished titanium and vanadium surfaces concerning three aspects.
First, the surface topography on the scale of proteins and cells is examined then chemical impurities on the
surface will be studied. Finally, the hydroxylation state will be looked at. Authors also state titanium is well
accepted by tissue while vanadium is inherently toxic. Results conclude that the main physico-chemical surface
properties influencing the adsorption of water and proteins have been measured for electropolished Ti and V.
Authors have evaluated the problems of contamination due to segregation that could appear when using
electropolished Ti for implantation. No striking differences between titanium and vanadium have been observed
concerning the topography, the surface chemical composition and the hydroxylation state that could easily be
related to the very different biological response of these two materials.
Hsu et. al. [20] says commercial pure titanium (cp-Ti) has good in vitro and in vivo biocompatibility. Many
surface treatments have been implemented on cp-Ti to improve bone-implant interface. Thus, cp-Ti surfaces
were prepared to enable machined surfaces (TM) to be compared to the machined, sandblasted, laser
irradiated and dual-acid etched surfaces (TA). Biocompatibility was evaluated in vitro by cytotoxicity testing of
the extracts. Cellular attachment and surface growth was also examined. Results showed acid etching
increased concentrations of O and reduced C, Ti, and N and TA was more thoroughly oxidized than TM.
Cytotoxicity results show that the metabolic activity of cells in both the blank group and the test group
increased over time and did not differ from each other, indicating TA and TM display not cytotoxic effect.
Implantation of the titanium into rabbit tibias to assess mechanical properties concluded the experimentation.
The animal model found TA implants had a much larger torque than TM implants. Overall, authors found the
TA implant to be superior to the TM implant.
Surface topography can also be due to the titanium dioxide film formed on the surface of titanium. Thull [21]
says refractory metals such as titanium, zirconium, niobium, tantalum and their alloys used for implants are
characterized by very low disintegration rates. This justifies the question as to the details of how
physicochemical communication between material surfaces and the extracellular matrix occurs. Results find
for a titanium surface covered with a thin titanium dioxide film, 𝑂𝐻 − ions are attracted to the polarized titanium
atoms at the surface, this is the Lewis acid sites of the solid. The 𝐻 + ions are attracted to the polarized oxygen
atoms; the Lewis base sites. A net negative charge results from the first reaction while the second reaction has
a net positive charge. An overall charge is dependent on the pH of the solution. Overall, the authors conclude
that the molecular biological methods that an undestroyed oxide layer of anatase on titanium through
passivation leaves the albumin conformational unchanged.

Concerns of hypersensitivity to titanium have been raised in the materials history of usage.
Sicilia et. al. [4] aims to assess the presence of titanium allergy by the anamnesis and medical examination
and analyzing eventual positive results that could occur. Results found that out of the 1500 patients
assessed, only 9 showed a positive reaction to titanium which is a prevalence of 0.6%. Overall, authors
indicate that titanium allergies should be assessed then a medical professional should determine whether a
titanium implant is suitable for the patient. In continuation, Schultzel et. al. [22] also studies the reoccurrence
of metal hypersensitivity in orthopedic surgical patients. Further, a characterization of which metals patients
are most commonly hypersensitive to is made. In total, 41 patients were patch tested and 34 patients showed
a positive result to at least one metal. Only one patient tested positive for titanium metal allergy. When a
hypersensitivity to an implanted metal is detected, often the implant will be replaced with one made of
titanium. Another study of 546 patients found no positive tests for allergens in five titanium salts [23].
Hosoki et. al. [7] explores titanium dental implants on dental metal allergies based on individuals who went to
the DMA Clinic in Tokushima University Hospital. Results showed that 17 out of 270 patients tested positive for
a titanium allergy. Only 4 of the 17 patients had a titanium dental implant. These four patients displayed a
higher prevalence to the titanium allergen than the other 13. Suggesting that dental implants may increase a
risk of titanium sensitization. Overall, authors conclude that titanium has less prevalence as an allergen than
other metals but does indicate that it is possible to be allergic to titanium. Examination of patients with a history
of metal allergens is warranted before the implantation of a titanium implant.
Furrer et. al. [24] says that the number of total joint arthroplasties (TJA) is expected to increase by 300% to
600% by 2030. This rapid increase warrants further investigation into sensitization of titanium. The study
presents the extensiveness of sensitization to metals and bone cement components in patients with
osteosynthesis and TJA related complications. In addition, relevance and identification of potential allergens
were established. Results showed there were no positive patch test results for titanium in tests done for more
than 300 patients.
In conclusion, titanium displays a long history of safe use. Numerous studied have commended the material for
its biocompatibility citing no inflammatory response of cells. Use of titanium as far back as the 1940s indicated
titanium is well tolerated and accepted by the scientific community as an implantable material. No to very few
individuals have been identified as having hypersensitivity reactions to titanium. Therefore, wholistically,
titanium is a safe biomaterial that can used for implantable medical devices.
3. Literature Search Protocol
A literature search was performed with a beginning cut-off date of January 1, 1985 and an ending cut-off date
of July 26, 2021. The first search was performed in RightFind. Using the company collections, consisting of
Coloplast Print Book Collection, Elsevier Science Direct Corporate Edition, Elsevier Science Direct tokens, HMP,
MAG Online Library, Nature Tokens, Ovid, Royal Society of Chemistry Tokens, SpringerLink tokens, Taylor &
Francis Medical tokens, Taylor & Francis Science & Technology tokens, and Wiley Article Select tokens. In
addition, the exclude full text option was applied to this search. This feature does not search the full text article
for keywords; therefore, the keywords must be present in the abstract.
The search was performed using the following search string.
RightFind Search: (titanium) AND (properties) AND (application) AND (medical) AND (biocompatible) NOT
(coated) NOT (modified) NOT (blend)

• 79 results
• Rationale for exclusion of coated, blend and modified:
o Excluding these phrases allows for a narrowed approach. Coated, blend, and modified
signify a material that is not pure titanium, therefore, does not necessarily assess pure
titanium’s biocompatibility.
RightFind did not provide relevant adequate data for the clinical applications of ABS. So, PubMed was used to
find relevant data. PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) is a free online search engine for
biomedical literature that was developed and is maintained by the United States National Center for
Biotechnology Information (NCBI) at the United States National Library of Medicine (NLM) located at the United
States National Institutes of Health (NIH). It contains over 24 million citations from MEDLINE, life science
journals, and online books. MEDLINE is NLM’s bibliographic database containing citations and author abstracts
from more than 5,600 biomedical journals published in the United States and worldwide. Coverage extends
back to 1946. PubMed was chosen for its large collection of biomedical journal articles and references, as well
as its worldwide acceptance for scientific- and medicine-based searches.
The searches were performed using the following search strings.
PubMed Search #1: ("titanium") AND ("in vitro" OR "in vivo") AND ("implant") AND (cytotoxicity) AND
(biocompatible) NOT (coated) NOT (modified) NOT (novel)
• 37 results
PubMed Search #2: ("titanium") AND (toxicity) AND (chronic OR acute) AND ("implant") AND
(biocompatible) NOT (coated) NOT (modified) NOT (novel)
• 3 results
PubMed Search #3: ("titanium") AND ("hypersensitivity") AND ("allergy") NOT (coated) NOT (modified)
NOT (novel)
• 87 results
There was no overlap of among the searches. No additional articles potentially relevant to this topic were found
during abstract review.
The following selection criteria were applied to the citations identified in the search results. Articles meeting
the criteria based on abstract review were obtained for full text review. Final determination of article eligibility
was made upon review of the full text.
Selection criteria:
• Published through 1/1985 to 7/2021
• Full text article available
• English language
• Evaluated the biosafety components of titanium.
• Includes studies of biocompatibility.

Articles were excluded for the following reasons:
• Review articles, not original work.
• Case studies. These only provide a single insight to the impacts of titanium.
• Presentations, posters, and abstracts
• Off-topic
o Composites/blends/modified titanium not compared to pure titanium.
4. Literature Search Results
Overall, a total of 206 citations were obtained from the literature searches. Following the application of the
selection criteria described above and abstract and full-text review, 182 citations were excluded and placed in
Annex X. This search and subsequent review resulted in 24 publications selected for summarization and crafted
into a review of the material, titanium.
5. Critical Evaluation of the Literature
Articles not excluded are summarized below. These articles also are also used in the development of the
titanium biocompatibility review. This review is to be a part of the Biological Evaluation Plan.
1. Moller
Moller et. al. [9] says titanium has been a prominent material for dental implants for around the past 30 years
due to relatively high success rates. It is rare to find an individual who is allergic to titanium even literature only
purely describes case studies. A drawback of titanium implants in dental implants is that the implant could look
potentially aesthetically unpleasing. Investigated in this study is titanium compared to zirconium dioxide
implants with respect to their biocompatibility in cell cultures. Osseointegration in adult domestic pigs was also
studied in vivo. One zirconium implant and five different titanium implants were studied. Results showed after
incubation with the eluates, all samples showed cell viability. Lactate dehydrogenase tests showed high
cytotoxic effect in one titanium implant at the 10 minute and 1 hour eluate but not in the 24-hour eluate. An
MTT-test showed high activity with the eluate from all implants. SEM examination displayed that the cells
cultivated on the implant surface had good contact in all implants. All animals that participated in the tests
showed normal eating behavior after surgery nor were there any signs of infection. Microradiographically and
histologically there was no connective tissue sheath observed on the implants. After 12 weeks it was found that
the tissue was re-established as lamellar bone in the contact zone of all implants.
2. Goodman
Goodman et. al. [13] aim to form a qualitative and quantitative histological analysis of the response of bone to
two commonly used orthopedic materials in two different physical forms. A group of 7 rabbits received
commercially pure titanium that was atraumatically wound into a helical shape then implanted into the
proximal tibia through a 6mm drill hole. A second group of 7 rabbits received commercially pure titanium
particles. Results showed that the titanium wire implants were surrounded by a variable, hypocellular fibrous
tissue layer. Particulate implants of titanium displayed gross clumping of the implant. In addition, particles were
separated from the main implant with metallic particles present within the cells. Foreign body reaction and
inflammatory cells were not present. Overall, this study finds that bulk and particulate forms of titanium in an
intraosseous location display incomplete fibrous encapsulation in a background of normal bone marrow.
Foreign body and inflammatory responses were not detected.

3. Gardin
Gardin et. al. [5] shares that titanium is one of the most widely used biomaterials for dental implants due to its
excellent mechanical strength and chemical stability. The material is highly biocompatibility due to its low-
toxicity and low rate of ion release from its surface. Titanium is well used because of its osseointegration, the
formation of a strong connection between the implant surface and the surrounding host bone. This study
specifically aims to investigate influence of grit- blasted and acid- etched titanium implants surface on the
biological response of human mesenchymal stem cells (MSCs) using in vitro tests. Results show no mutagenic
activity, and the hemolysis index was less than 2% meaning that there was an absence of any hemolytic activity.
Biocompatibility was evaluated by cultivating adipose tissue onto the surfaces of titanium for up to 30 days. A
MTT assat showed that the cells were able to adhere and proliferate on the titanium, no chromosomal
alterations are present in the adipose tissue seeded onto the titanium for 30 days, and the expression of some
osteoblast markers in adipose tissue seeded onto titanium dental implants is higher when compared to the
control. To conclude, the results find that titanium implants are not mutagenic, do not cause hemolysis, their
surfaces are biocompatible and non-toxic when seeded with adipose tissue.
4. Sirak
Sirak et. al. [14] assess the bone ingrowth into porous titanium granules used for maxillary sinus augmentation
in the sheep maxillary sinus augmentation model. Twelve sheep were used in this study. The sheep were
injected with infiltration anesthesia then a layer-by-layer dissection of skin and muscle fascia offered proper
access to the experimental area. Histopathological photomicrographs revealed that at 30 days the titanium
granules were overgrown and integrated in connective tissue fibers. The rough surface as well as the high
porosity of the titanium granules promoted active migration of fibroblasts in addition to contributing to an
efficient vascularization. Monocytes, macrophages and connective tissue fibroblasts accumulated at the
titanium granules sites. No inflammatory response was observed, and high magnification displayed the
ingrowth. Further, the histological observation at 90 days showed trabecular bone growth indicating the
titanium granules act as an osteoconductive scaffold when placed in bone marrow. At 3 months post
implantation, newly formed bone of the defect could have been easily seen titanium granules well incorporated
into the bone matrix. Overall, the author cite that porous titanium granules are biocompatible with bone tissue
in the large animal model.
5. Meng
Meng et. al. [2] says that titanium is high strength, toughness, durability, corrosion resistance, and better
biocompatibility. These qualities make titanium useful in orthopedic and dental implants. Many studies have
been completed on wear debris and bone lysis; these studies have concluded that titanium wear particles from
the surfaces of the implants were considered to play a major role in aseptic loosening. This study attempts to
evaluate the effect of titanium particles on rat bone marrow stem cells in vitro. An assay was performed to
evaluate the effect of titanium particles on bone marrow mesenchymal stem cells (BMSCs) viability. Significant
does dependence on the decrease of cells was observed. Viability of 48 hours with titanium particles was less
than 24 hours. Therefore, a dose and time dependence were observed for BMSCs viability. Overall, authors say
these findings support the initial hypothesis that titanium particles had a cytotoxicity on BMSCs in vitro with
decrease viability and proliferation. These results could be partly due to the phagocytosis of titanium particles
and the damage of cell skeleton protein.

6. Lu
Lu et. al. [10] claims titanium and titanium alloys are used in orthopedic and dental implant fabrication.
Investigated in this study is the evaluation of the suitability of a nano-grained surface layer on a commercially
pure titanium sheet. Surface characteristics, biocompatibility, and in vitro corrosion behavior were investigated
and compared to coarse-grained substrate. Results show a fantastic combination of in vitro biological and anti-
corrosion and biocompatibility properties were achieved by the nano-grained surface layer on pure titanium.
7. Kubacka
Kubacka et. al. [3] shares that titanium and its alloys are important to the biomedical field because of its strong
biocompatibility, high corrosion resistance in body fluid, and low Young’s modulus. Pure titanium is more
attractive because its alloys can contain toxic elements such as vanadium and aluminum. However, the
disadvantage of pure titanium that it has insufficient mechanical strength for most applications. Particularly,
this study focuses on the impact of grain refinement on cellular response and protein adsorption behavior on
commercially pure (CP) titanium (Ti), CP Ti subject to hydrostatic extrusion 6 times (Ti6) and 10 times (T10).
Results find similar levels of cell viability were found for the CP Ti and Ti6 for all incubation periods. Overall, the
research shows CP Ti, Ti6, and Ti10 have similar levels of biocompatibility.
8. Heakal & Shehata
Heakal & Shehata et. al. [8] describes the passive films on titanium and its alloys that allow them to excellently
satisfy their biocompatibility because the films are characterized by their spontaneous formation, adherence,
self-heating, and stability. This work specifically looks at electrochemical behavior of the native surface oxide
layers on titanium and its alloy, Ti-6Al-4V, in buffer solutions of different pH. Authors find the oxide films grown
spontaneously in borate buffer solutions on titanium are more stable than the ones grown on its alloy. In
addition, polarization resistance of titanium increases with increasing pH but the opposite is true for the alloy.
9. Grenade
Grenade et. al. [18] says that biocompatibility of implant materials with soft tissues constitutes a critical
parameter. More recently, advancements have been made in computer aided design and computer aided
manufacturing (CAD-CAM), introducing composite materials in addition to alloys, mainly titanium and ceramic
materials. This study firstly looks at biocompatibility of PICNs in comparison to metallic and ceramic materials
used for dental implant prostheses while assessing HGK attachment, proliferation and spreading. Secondly the
study correlates results with PICN UDMA release and indirect cytotoxicity. In conclusion the results display the
current excellent behavior of presently used materials in implant prosthodontics such as titanium. Authors say
titanium and zirconia are considered the gold standard materials in terms of gingival cell behavior.
10. Williams
Williams [1] opens with a quotation from Promisel, “Never has there been, as in the case of titanium, the
concentration of scientific and technical devotion to a single metal . . . never has metal, normally considered so
mundane, been so extravagantly described as the wonder metal and the metal of promise.” In the 1940s the
first surgical experimentation with titanium was reported, tolerance to titanium indicated a positive response.
In 1951, a different study displayed good tissue tolerance in rabbits. Eventually, an alloy was developed from
the pure titanium to create a material with better mechanical properties. The alloy, Ti-6Al-V, is highly discussed

in this document. Corrosion properties of titanium have proved to be superior. The metal provides nearly
perfect corrosion resistance in neutral solutions.
11. Wang
Wang [12], again, states titanium was first used in surgical applications in the 1940s. Early researchers found
titanium to have excellent tissue compatibility. In the early 1970s, titanium and its alloys began gaining
widespread usage as an implant material. Commercially pure titanium has high resistance and tissue tolerance;
however, the material has a much lower strength and unfavorable wear properties. The paper concludes that
commercially pure titanium and its alloys are widely used in medical applications.
12. Thull
Thull [21] says refractory metals such as titanium, zirconium, niobium, tantalum and their alloys used for
implants are characterized by very low disintegration rates. This justifies the question as to the details of how
physicochemical communication between material surfaces and the extracellular matrix occurs. Results find
for a titanium surface covered with a thin titanium dioxide film, 𝑂𝐻 − ions are attracted to the polarized titanium
atoms at the surface, this is the Lewis acid sites of the solid. The 𝐻 + ions are attracted to the polarized oxygen
atoms; the Lewis base sites. A net negative charge results from the first reaction while the second reaction has
a net positive charge. An overall charge is dependent on the pH of the solution. Overall, the authors conclude
that the molecular biological methods that an undestroyed oxide layer of anatase on titanium through
passivation leaves the albumin conformational unchanged.
13. Thomas
Thomas et. al. [6] shares titanium has repeated daily contact to titanium in the form of 𝑇𝑖𝑂2 . 𝑇𝑖𝑂2 is found in
paints, whitening agents, sunscreens, and skin care products. Titanium is also used in the industrial field such
as the metallurgic, pharmaceutical, and food industries. In addition, titanium-based materials can be used in
orthopedics and dental implantation because the material offers a high rate of osseointegration. Limited cases
have been reported regarding hypersensitivity to titanium. Historically, titanium has been found to be
biologically inert, yet, more recently questions have been raised on titanium-based implants undergoing
biocorrosion. This study first investigates the inflammatory mediator production and LTT reactivity of human
lymphocytes and monocytes that were exposed to titanium particles and discs in vitro. A second aim of the
study is to assess the potential variations of this response in healthy individuals with no symptoms with titanium
dental implants. Titanium particles used were commercially pure titanium dioxide. This is because metallic
titanium spontaneously oxidizes to titanium dioxide in air or water and forms a protective surface layer to
prevent further oxidation. The study also used commercially available titanium metal discs. Authors find the
released titanium may be detected in the tissues surrounding joint replacement and lymph nodes in association
with titanium screws or mini plats. In the case of dental implants, titanium is encounters in tissues that lie
adjacent to these dental implants. Overall, authors conclude that little is known about the immune mechanisms
that lead to well-tolerated titanium dental implants. Their results display that adaptive mechanisms my exist,
therefore, future studies will show factors and cell populations add to this protective tolerance.
14. Thewes
Thewes et. al. [15] aims to study were to compare the number of total cells as well as different cell subgroups
and characterize the cells of perivascular infiltration in tissue adjacent to steel and titanium implants. Results
found no difference between steel and titanium implants regarding the perivascular cell infiltration in the

adjacent tissue. In conclusion, authors say it is better to remove steel implants when clinical complications arise
after osteosynthesis and after bone-healing begins in order to prevent and allergic reaction. For titanium,
authors find it is best to remain in situ.
15. Szuhanek
Szuhanek et. al. [16] assesses the biosecurity of one stainless steel implant and two titanium-based implants by
means of extraction in terms of cell morphological aspects, cell viability, and cytotoxicity. The in vitro model
was used by employing primary human gingival fibroblasts (HGFs) cells. P3 was identified as a titanium implant.
Results on the SEM analysis showed P3 has a microstructure with a porous surface, with elevations and
depressions. HGF cells did not show significant changes with P3 compared to control cells in 72 hours and the
viability of HGF cells when exposed to P3 was 98.37%. Cytotoxic effects were not significant in P3. Overall, the
authors conclude the titanium implants investigated in this study did not show cytotoxicity of HGF cell
population and toxicological data show no toxicity. These effects demonstrate a biosafe profile.
16. Sicilia
Sicilia et. al. [4] says titanium has high resistance to corrosion in a physiological environment and an excellent
biocompatibility that gives it a passive, stable oxide film, and, therefore, is used extensively in the medical field.
This study specifically aims at assessing the presence of titanium allergy by the anamnesis and medical
examination and analyzing eventual positive results that could occur. Results found that out of the 1500
patients assessed, only 9 showed a positive reaction to titanium which is a prevalence of 0.6%. Overall, authors
indicate that titanium allergies should be assessed then a medical professional should determine whether a
titanium implant is suitable for the patient.
17. Kunert-Keil
Kunert-Keil et. al. [17] completed an in vitro study in order to evaluate the biocompatibility of a novel zirconium
implant surface in comparison to both commercially available zirconium and titanium implants. Results
displayed that the titanium implants had a higher surface roughness and heterogeneity than the new ceramic
implants. In addition, no significant difference in the number of dead cells among all implants. The rough surface
of the titanium implant has an impact on its ability to anchor to bone.
18. Hosoki
Hosoki et. al. [7] shares titanium metal is passivated with a chemically stable titanium oxide in order to produce
a highly biocompatible biomaterial that is chemically stable and non-corrosive. The material has been widely
used in plastic surgery and dental implants because it was considers a non-allergenic metal. Explored in this
study is titanium dental implants on dental metal allergies based on individuals who went to the DMA Clinic in
Tokushima University Hospital. Results showed that 17 out of 270 patients tested positive for a titanium allergy.
Only 4 of the 17 patients had a titanium dental implant. These four patients displayed a higher prevalence to
the titanium allergen than the other 13. Suggesting that dental implants may increase a risk of titanium
sensitization. Overall, authors conclude that titanium has less prevalence as an allergen than other metals but
does indicate that it is possible to be allergic to titanium. Examination of patients with a history of metal
allergens is warranted before the implantation of a titanium implant.

19. Furrer
Furrer et. al. [24] says that the number of total joint arthroplasties (TJA) is expected to increase by 300% to
600% by 2030. This rapid increase warrants further investigation into sensitization of titanium. The study
presents the extensiveness of sensitization to metals and bone cement components in patients with
osteosynthesis and TJA related complications. In addition, relevance and identification of potential allergens
were established. Results showed there were no positive patch test results for titanium in tests done for more
than 300 patients.
20. Serra
Serra et. al. [11] shares that commercially pure titanium (cpTi) is commonly used in dental implantology
because of its excellent results in animal studies and in humans. Integration development between cpTi and
bone allow for titanium to be an excellent biomaterial. Explored in this study is a novel titanium and is compared
to the conventional cpTi. The study processes nanostructured titanium then mechanically compares novel
titanium, cpTi, and Ti-6Al-4V, and assesses surface morphology and the fracture surface characteristics.
Results indicate that cpTi is commonly used in mini implants, however, the small size results in numerous
fractures. In addition, the biocompatibility of cpTi is largely due to the oxide film formed on its surface, this layer
is composed of 𝑇𝑖𝑂2 . In conclusion, the study finds the novel titanium includes the biocompatibility cpTi mini
implants and it is suggested that the novel titanium can be used as a base in orthopedic implants.
21. Schultzel
Schultzel et. al. [22] studies the reoccurrence of metal hypersensitivity in orthopedic surgical patients. Further,
a characterization of which metals patients are most commonly hypersensitive to is made. In total, 41 patients
were patch tested and 34 patients showed a positive result to at least one metal. Only one patient tested
positive for titanium metal allergy. When a hypersensitivity to an implanted metal is detected, often the implant
will be replaced with one made of titanium.
22. Linauskienė
Linauskienė et. al. [23] investigates the prevalence of contact allergy to metals in patients with suspected
allergic contact dermatitis (ACD) at Vilnius University Hospital Santariskiu Klinikos. Then compares compiled
data with published results from other countries. Results find no positive tests for the five titanium salts tested.
Authors claim this could be due to the small testing pool of 546 patients.
23. Jobin
Jobin et. al. [19] aims to compare electropolished titanium and vanadium surfaces concerning three aspects.
First, the surface topography on the scale of proteins and cells is examined then chemical impurities on the
surface will be studied. Finally, the hydroxylation state will be looked at. Authors also state titanium is well
accepted by tissue while vanadium is inherently toxic. Results conclude that the main physico-chemical surface
properties influencing the adsorption of water and proteins have been measured for electropolished Ti and V.
Authors have evaluated the problems of contamination due to segregation that could appear when using
electropolished Ti for implantation. No striking differences between titanium and vanadium have been observed
concerning the topography, the surface chemical composition and the hydroxylation state that could easily be
related to the very different biological response of these two materials.

24. Hsu
Hsu et. al. [20] says commercial pure titanium (cp-Ti) has good in vitro and in vivo biocompatibility. Many
surface treatments have been implemented on cp-Ti to improve bone-implant interface. Thus, cp-Ti surfaces
were prepared to enable machined surfaces (TM) to be compared to the machined, sandblasted, laser
irradiated and dual-acid etched surfaces (TA). Biocompatibility was evaluated in vitro by cytotoxicity testing of
the extracts. Cellular attachment and surface growth was also examined. Results showed acid etching
increased concentrations of O and reduced C, Ti, and N and TA was more thoroughly oxidized than TM.
Cytotoxicity results show that the metabolic activity of cells in both the blank group and the test group
increased over time and did not differ from each other, indicating TA and TM display not cytotoxic effect.
Implantation of the titanium into rabbit tibias to assess mechanical properties concluded the experimentation.
The animal model found TA implants had a much larger torque than TM implants. Overall, authors found the
TA implant to be superior to the TM implant.
6. Biocompatibility Literature Review Conclusions
The selected 24 articles above demonstrate biocompatibility viewpoints from 4 continents and 18 varying
countries. Therefore, we can say our search represents a wholistic view of the biocompatibility of titanium. No
authors are repeated, meaning one opinion is not overshadowing the opinions of the broader community.
Titanium is regarded as a highly biocompatible material with minimal hypersensitivity response. Little to no
inflammatory response has been documented in the abundance of studies completed on titanium. Therefore,
as the broad community of scientists have agreed that titanium is biocompatible and safe for use in the human
body.
7. References
1. Williams, D.F., Titanium as a metal for implantation. Part 1: physical properties. J Med Eng Technol,
1977. 1(4): p. 195-8, 202 contd.
2. Meng, B., et al., The effect of titanium particles on rat bone marrow stem cells in vitro. Toxicol Mech
Methods, 2009. 19(9): p. 552-8.
3. Kubacka, D., et al., Biological behavior of titanium processed by severe plastic deformation. Applied
Surface Science, 2019. 472: p. 54-63.
4. Sicilia, A., et al., Titanium allergy in dental implant patients: a clinical study on 1500 consecutive
patients. Clin Oral Implants Res, 2008. 19(8): p. 823-35.
5. Gardin, C., et al., Adult stem cells properties in terms of commitment, aging and biological safety of
grit-blasted and Acid-etched ti dental implants surfaces. Int J Mol Cell Med, 2014. 3(4): p. 225-36.
6. Thomas, P., et al., Allergy or tolerance: reduced inflammatory cytokine response and concomitant
IL-10 production of lymphocytes and monocytes in symptom-free titanium dental implant patients.
Biomed Res Int, 2013. 2013: p. 539834.
7. Hosoki, M., et al., Cross-sectional observational study exploring clinical risk of titanium allergy caused
by dental implants. J Prosthodont Res, 2018. 62(4): p. 426-431.
8. Heakal, F. and O. Shehata, Insight into the Electrochemical and Semiconducting Properties of Native
Oxide Films on Ti Metal and Its Ti–6Al–4V Alloy in Borate Buffer Solutions. Protection of Metals and
Physical Chemistry of Surfaces, 2020. 56.
9. Möller, B., et al., A comparison of biocompatibility and osseointegration of ceramic and titanium
implants: an in vivo and in vitro study. Int J Oral Maxillofac Surg, 2012. 41(5): p. 638-45.

10. Lu, J., et al., Electrochemical corrosion characteristics and biocompatibility of nanostructured
titanium for implants. Applied Surface Science, 2018. 434: p. 63-72.
11. Serra, G., et al., Nanostructured severe plastic deformation processed titanium for orthodontic mini-
implants. Materials Science and Engineering: C, 2013. 33(7): p. 4197-4202.
12. Wang, K., The use of titanium for medical applications in the USA. Materials Science and
Engineering: A, 1996. 213(1): p. 134-137.
13. Goodman, S.B., et al., The effects of bulk versus particulate titanium and cobalt chrome alloy
implanted into the rabbit tibia. J Biomed Mater Res, 1990. 24(11): p. 1539-49.
14. Sirak, S.V., et al., Osteogenic Potential of Porous Titanium. An Experimental Study in Sheep. J Natl
Med Assoc, 2019. 111(3): p. 310-319.
15. Thewes, M., et al., Immunohistochemical characterization of the perivascular infiltrate cells in tissues
adjacent to stainless steel implants compared with titanium implants. Arch Orthop Trauma Surg,
2001. 121(4): p. 223-6.
16. Szuhanek, C.A., et al., Comparative Toxicological In Vitro and In Ovo Screening of Different
Orthodontic Implants Currently Used in Dentistry. Materials (Basel), 2020. 13(24).
17. Kunert-Keil, C., et al., The survival and proliferation of fibroblasts on ceramic implants: an in vitro
study. Biomed Tech (Berl), 2012. 57(1): p. 11-5.
18. Grenade, C., et al., Biocompatibility of polymer-infiltrated-ceramic-network (PICN) materials with
Human Gingival Keratinocytes (HGKs). Dent Mater, 2017. 33(3): p. 333-343.
19. Jobin, M., M. Taborelli, and P. Descouts, Surface properties of electropolished titanium and vanadium.
Applied Surface Science, 1993. 72(4): p. 363-372.
20. Hsu, S.H., et al., Characterization and biocompatibility of a titanium dental implant with a laser
irradiated and dual-acid etched surface. Biomed Mater Eng, 2007. 17(1): p. 53-68.
21. Thull, R., Physicochemical principles of tissue material interactions. Biomol Eng, 2002. 19(2-6): p. 43-
50.
22. Schultzel, M., et al., Incidence of Metal Hypersensitivity in Orthopedic Surgical Patients Who Self-
Report Hypersensitivity History. Perm J, 2020. 24.
23. Linauskienė, K., L. Malinauskienė, and A. Blažienė, Metals Are Important Contact Sensitizers: An
Experience from Lithuania. Biomed Res Int, 2017. 2017: p. 3964045.
24. Furrer, S., et al., Metal hypersensitivity in patients with orthopaedic implant complications-A
retrospective clinical study. Contact Dermatitis, 2018. 79(2): p. 91-98.
8. Annex X
Table 1: List of Excluded Documents and Rationale for Exclusion

# Authors Title Citation Rationale for Exclusion
1 Watari, F.; Biocompatibility of materials and Composites Science and After review of the
Yokoyama, A.; development to functionally graded Technology. 5/2004; vol. 64; abstract, the study
Omori, M.; implant for bio-medical application 893-908. DOI: examines a modified
Hirai, T.; 10.1016/j.compscitech.2003.0 titanium.
Kondo, H.; Uo, 9.005
M.; Kawasaki,
T.
2 Zhang; Chu; Fabrication of high strength, Materials Science & After review of the
He; Wang; Zhu; antibacterial and biocompatible Ti- Engineering C. 1/2020; vol. abstract, the study
Ren 5Mo-5Ag alloy for medical and 106. DOI: examines a modified
surgical implant applications 10.1016/j.msec.2019.110165 titanium.

3 Kim; Park; Antibacterial and bioactive Applied Surface Science. After review of the
Cheon; Jung; properties of stabilized silver on 9/1/2018; vol. 451; 232-240. abstract, the study
Song; Kim; Jang titanium with a nanostructured DOI: examines a coated
surface for dental applications 10.1016/j.apsusc.2018.04.270 titanium.
4 Khan, S.; Ul- Bacterial cellulose-titanium dioxide Cellulose. 2/2015; vol. 22; After review of the
Islam, M.; nanocomposites: nanostructural 565-579. DOI: abstract, the study
Khattak, W.; characteristics, antibacterial 10.1007/s10570-014-0528-4 examines a modified
Ullah, M.; Park, mechanism, and biocompatibility titanium.
J.
5 Gordin, D.M.; Design of a nitrogen-implanted Materials Science & After review of the
Busardo, D.; titanium-based superelastic alloy Engineering C. 10/2013; vol. abstract, the study
Cimpean, A.; with optimized properties for 33; 4173-4182. DOI: examines a modified
Vasilescu, C.; biomedical applications 10.1016/j.msec.2013.06.008 titanium.
Hoche, D.;
Drob, S.I.;
Mitran, V.;
Cornen, M.;
Gloriant, T.
6 Mechanical Mechanical properties of a medical Materials Science & After review of the
properties of a @b-type titanium alloy with specific Engineering C. 7/1/2013; vol. abstract, the study
medical @b- microstructural evolution through 33; 1499-2507. DOI: examines a modified
type titanium high-pressure torsion 10.1016/j.msec.2013.01.056 titanium.
alloy with
specific
microstructural
evolution
through high-
pressure
torsion
7 Ayobian- Effects of Er: YAG laser irradiation Lasers in Medical Science. After review of the
Markazi, N.; on wettability, surface roughness, 2/2015; vol. 30; 561-566. DOI: abstract, the study
Karimi, M.; and biocompatibility of SLA 10.1007/s10103-013-1361-y examines a modified
Safar- titanium surfaces: an in vitro study titanium.
Hajhosseini, A.
8 Kaur; Singh Review on titanium and titanium Materials Science & Review article.
based alloys as biomaterials for Engineering C. 9/2019; vol.
orthopaedic applications 102; 844-862. DOI:
10.1016/j.msec.2019.04.064
9 Huang, J.; Systematic evaluation of selective International Journal of After review of the
Chang, C.; fusion additive manufacturing Advanced Manufacturing abstract, the study
Wang, W.; based on thermal energy source Technology. 8/2020; vol. 109; examines a modified
Chou, M.; applied in processing of titanium 2421-2429. DOI: titanium.
Tseng, C.; Tu, alloy specimens for medical 10.1007/s00170-020-05797-
P. applications 7
10 Mishnaevsky, Nanostructured titanium-based Materials Science & After review of the
L.; Levashov, materials for medical implants: Engineering R. 7/2014; vol. 81; abstract, the study
E.; Valiev, R.Z.; Modeling and development 1-19. DOI: examines a modified
Segurado, J.; 10.1016/j.mser.2014.04.002 titanium.

Sabirov, I.;
Enikeev, N.;
Prokoshkin, S.;
Solov'yov, A.V.;
Korotitskiy, A.;
Gutmanas, E.;
Gotman, I.;
Rabkin, E.;
Psakh'e, S.;
Dluhos, L.;
Seefeldt, M.;
Smo
11 Li, B.; Li, Y.; Li, Improvement of biological Applied Surface Science. After review of the
J.; Fu, X.; Li, C.; properties of titanium by anodic 7/15/2014; vol. 307; 202-208. abstract, the study
Wang, H.; Liu, oxidation and ultraviolet irradiation DOI: examines a modified
S.; Guo, L.; Xin, 10.1016/j.apsusc.2014.04.015 titanium.
S.; Liang, C.; Li,
H.
12 Gordin, D.M.; Potentiality of the ''Gum Metal'' Materials Science & After review of the
Ion, R.; titanium-based alloy for biomedical Engineering C. 11/1/2014; vol. abstract, the study
Vasilescu, C.; applications 44; 362-370. DOI: examines a modified
Drob, S.I.; 10.1016/j.msec.2014.08.003 titanium.
Cimpean, A.;
Gloriant, T.
13 Pham; Jun; Kim; Deposition of titanium nitride (TiN) Applied Surface Science. After review of the
Koh on Co–Cr and their potential 1/15/2012; vol. 258; 2864- abstract, the study
application as vascular stent 2868. DOI: examines a modified
10.1016/j.apsusc.2011.10.149 titanium.
14 Mavros; Spark plasma sintering of low Materials & Design. After review of the
Larimian; modulus titanium-niobium- 12/5/2019; vol. 183. DOI: abstract, the study
Esqivel; Gupta; tantalum-zirconium (TNTZ) alloy 10.1016/j.matdes.2019.10816 examines a modified
Contieri; Borkar for biomedical applications 3 titanium.
15 Ghosh; Selective laser melted titanium Journal of the Mechanical After review of the
Abanteriba; alloys for hip implant applications: Behavior of Biomedical abstract, the study
Wong; Surface modification with new Materials. 11/2018; vol. 87; examines a modified
Houshyar method of polymer grafting 312-324. DOI: titanium.
10.1016/j.jmbbm.2018.07.031
16 Spajić; Rodič; The effect of surface preparation Electrochimica Acta. After review of the
Šekularac; on the protective properties of 1/10/2021; vol. 366. DOI: abstract, the study
Lekka; Fedrizzi; Al2O3 and HfO2 thin films 10.1016/j.electacta.2020.137 examines a modified
Milošev deposited on cp-titanium by atomic 431 titanium.
layer deposition
17 Fasching, An Evaluation of a NiTiCo Alloy and Journal of Materials After review of the
Audrey; its Suitability for Medical Device Engineering and Performance. abstract, the study
Norwich, D.; Applications 7/2011; vol. 20; 641-645. DOI: examines a modified
Geiser, T.; Paul, 10.1007/s11665-011-9845-z titanium.
Graeme W.

18 Hussein; Biocompatibility of new Ti–Nb–Ta Materials Science & After review of the
Gepreel; base alloys Engineering C. 4/1/2016; vol. abstract, the study
Gouda; 61; 574-578. DOI: examines a modified
Hefnawy; 10.1016/j.msec.2015.12.071 titanium.
Kandil
19 Oh, Keun‐Taek; Cytocompatibility and Journal of Biomedical Materials After review of the
Kang, Dong‐ electrochemical properties of Ti–Au Research Part B: Applied abstract, the study
Kuk; Choi, alloys for biomedical applications Biomaterials. 10/1/2007; vol. examines a modified
Good‐Sun; Kim, 83B; 320-326. DOI: titanium.
Kyoung‐Nam 10.1002/jbm.b.30798
20 Málek; Starý The correlation between substrate Applied Surface Science. After review of the
and deposited biocompatible layer 11/30/2018; vol. 459. 114- abstract, the study
microstructures on different 119. DOI: examines a coated
substrates 10.1016/j.apsusc.2018.07.186 titanium.
21 Tschernitschek, Nonalloyed titanium as a bioinert Journal of Prosthetic Dentistry. Review article.
H.; Borchers, L.; metal-A review 7/2006; vol. 96; 12. DOI:
Geurtsen, W. 10.1016/j.prosdent.2006.02.0
20
22 Tian, Y.S.; Research progress on laser surface Applied Surface Science. After review of the
Chen, C.Z.; Li, modification of titanium alloys 3/31/2005; vol. 242; 177-184. abstract, the study
S.T.; Huo, Q.H. DOI: examines a modified
10.1016/j.apsusc.2004.08.011 titanium.
23 Yu; Yang; Investigating the effect of Journal of Materials Processing After review of the
Zhang; Hu picosecond laser texturing on Tech. 5/2018; vol. 255; 129- abstract, the study
microstructure and 136. DOI: examines a modified
biofunctionalization of titanium 10.1016/j.jmatprotec.2017.12. titanium.
alloy 009
24 Chen; Pan; Joint wound healing using polymeric Materials Letters. 6/1/2020; After review of the
Zhuang; Peng; dressing of chitosan/strontium- vol. 268. DOI: abstract, the study
Zhang doped titanium dioxide with high 10.1016/j.matlet.2020.12755 examines a modified
antibacterial activity 5 titanium.
25 Lin; Li; Li; Micro-dot-matrix induced by Applied Surface Science. After review of the
Zhang; Cui femtosecond laser on titanium 1/1/2020; vol. 499. DOI: abstract, the study
surface for Ca-P phase deposition 10.1016/j.apsusc.2019.14392 examines a modified
5 titanium.
26 Henderson, E.; On the experimental testing of fine Journal of the Mechanical After review of the
Nash, D.H.; Nitinol wires for medical devices Behavior of Biomedical abstract, the study
Dempster, W.M. Materials. 4/2011; vol. 4; 261- examines a modified
268. DOI: titanium.
10.1016/j.jmbbm.2010.10.004
27 Cremasco, A.; Electrochemical corrosion behavior Electrochimica Acta. After review of the
Osorio, W.R.; of a Ti-35Nb alloy for medical 5/30/2008; vol. 53; 4867- abstract, the study
Freire, C.M.A.; prostheses 4874. DOI: examines a modified
Garcia, A.; 10.1016/j.electacta.2008.02.0 titanium.
Caram, R. 11
28 Seitz, Jan‐ Recent Advances in Biodegradable Advanced Healthcare Review article.
Marten; Durisin, Metals for Medical Sutures: A Materials. 9/17/2015; vol. 4;
Martin; Critical Review

Goldman, 1915-1936. DOI:
Jeremy; Drelich, 10.1002/adhm.201500189
Jaroslaw W.
29 Clarke, B.; Effect of nitinol wire surface Acta Biomaterialia. 1/2007; After review of the
Kingshott, P.; properties on albumin adsorption vol. 3; 103-111. DOI: abstract, the study
Hou, X.; 10.1016/j.actbio.2006.07.006 examines a modified
Rochev, Y.; titanium.
Gorelov, A.;
Carroll, W.
30 Hu, Guoqing; Engineered Functional Surfaces by Engineering (Beijing). 12/2018; After review of the
Guan, Kai; Lu, Laser Microprocessing for vol. 4; 822-830. DOI: abstract, the study
Libin; Zhang, Biomedical Applications 10.1016/j.eng.2018.09.009 examines a modified
Jiaru; Lu, Nie; titanium.
Guan,
Yingchun
31 Verestiuc; New Ti–Mo–Si materials for bone Journal of the Mechanical After review of the
Spataru; prosthesis applications Behavior of Biomedical abstract, the study
Baltatu; Materials. 1/2021; vol. 113. examines a modified
Butnaru; DOI: titanium.
Solcan; Sandu; 10.1016/j.jmbbm.2020.10419
Voiculescu; 8
Geanta;
Vizureanu
32 Trinidad, J.; Processing of Magnesium Porous Advanced Engineering After review of the
Marco, I.; Structures by Infiltration Casting for Materials. 2/17/2014; vol. 16; abstract, the study
Arruebarrena, Biomedical Applications 241-247. DOI: examines a modified
G.; Wendt, J.; 10.1002/adem.201300236 titanium.
Letzig, D.;
Sáenz de
Argandoña, E.;
Goodall, R.
33 Mostaed; Zinc-based alloys for degradable Acta Biomaterialia. After review of the
Sikora-Jasinska; vascular stent applications 4/15/2018; vol. 71; 1-23. DOI: abstract, the study
Drelich; Vedani 10.1016/j.actbio.2018.03.005 examines a modified Zn.
34 Slokar, L.; Alloy design and property Materials and Design. 1/2012; After review of the
Matkovic, T.; evaluation of new Ti-Cr-Nb alloys vol. 33; 26-30. DOI: abstract, the study
Matkovic, P. 10.1016/j.matdes.2011.06.05 examines a modified
2 titanium.
35 Wang, Rex; Effects of nanometric roughness on Biointerphases. 9/2011; vol. 6; After review of the
Hsieh, Ming- surface properties and fibroblast's 87-97. DOI: abstract, the study
Che; Lee, Tzer- initial cytocompatibilities of Ti6AI4V 10.1116/1.3604528 examines a modified
Min titanium.
36 Koike, M.; Evaluation of cast Ti-Fe-O-N alloys Materials Science & After review of the
Ohkubo, C.; for dental applications Engineering C. 5/2005; vol. 25; abstract, the study
Sato, H.; Fujii, 349-356. DOI: examines a modified
H.; Okabe, T. 10.1016/j.msec.2005.04.002 titanium.

37 Talha, M.; A review on nickel-free nitrogen Materials Science & Review article.
Behera, C.K.; containing austenitic stainless steels Engineering C. 10/2013; vol.
Sinha, O.P. for biomedical applications 33; 3563-3575. DOI:
10.1016/j.msec.2013.06.002
38 Khudhair; Anodization parameters influencing Materials Science & After review of the
Bhatti; Li; the morphology and electrical Engineering C. 2/1/2016; vol. abstract, the study
Hamedani; properties of TiO2 nanotubes for 59; 1125-1142. DOI: examines a modified
Garmestani; living cell interfacing and 10.1016/j.msec.2015.10.042 titanium.
Hodgson; investigations
Nahavandi
39 Kuczyńska- Biological properties of a novel β-Ti Applied Surface Science. After review of the
Zemła; alloy with a low young’s modulus 5/1/2020; vol. 511. DOI: abstract, the study
Kijeńska- subjected to cold rolling 10.1016/j.apsusc.2020.14552 examines a modified
Gawrońska; 3 titanium.
Chlanda;
Sotniczuk;
Pisarek;
Topolski;
Swieszkowski;
Garbacz
40 Agilan; In-vitro bioactivity and Applied Surface Science. After review of the
Rajendran electrochemical behavior of 5/1/2018; vol. 439; 66-74. abstract, the study
polyaniline encapsulated titania DOI: examines a modified
nanotube arrays for biomedical 10.1016/j.apsusc.2017.12.258 titanium.
applications
41 Cutolo; Mechanical properties of diamond Journal of the Mechanical After review of the
Engelen; lattice Ti–6Al–4V structures Behavior of Biomedical abstract, the study
Desmet; Van produced by laser powder bed Materials. 4/2020; vol. 104. examines a modified
Hooreweder fusion: On the effect of the load DOI: titanium.
direction 10.1016/j.jmbbm.2020.10365
6
42 Czarnowska; Structure and properties of nitrided Applied Surface Science. After review of the
Borowski; surface layer produced on NiTi 4/15/2015; vol. 334; 24-31. abstract, the study
Sowińska; shape memory alloy by low DOI: examines a modified
Lelątko; temperature plasma nitriding 10.1016/j.apsusc.2014.07.109 titanium.
Oleksiak;
Kamiński;
Tarnowski;
Wierzchoń
43 Wieland, M.; Wavelength-dependent Wear. 2/2000; vol. 237; 231- After review of the
Hanggi, P.; measurement and evaluation of 252. DOI: 10.1016/S0043- abstract, the study
Hotz, W.; surface topographies: application of 1648(99)00347-6 examines surface
Textor, M.; a new concept of window topographies.
Keller, B.A.; roughness and surface transfer
Spencer, N.D. function
44 Silva- Albumin adsorption on oxide thin Applied Surface Science. After review of the
Bermudez, P.; films studied by spectroscopic 12/15/2011; vol. 258; 1711- abstract, the study
ellipsometry

Rodil, S.E.; 1718. DOI: examines a modified
Muhl, S. 10.1016/j.apsusc.2011.10.020 titanium.
45 Danilov, Biocompatilibity-related surface Journal of Biomedical Materials After review of the
Anatoli; characteristics of oxidized NiTi Research Part A. 9/15/2007; abstract, the study
Tuukkanen, vol. 82A; 810-819. DOI: examines a modified
Tuomas; 10.1002/jbm.a.31190 titanium.
Tuukkanen,
Juha; J ms ,
Timo
46 Luz; Santos; Characterization of the Applied Surface Science. After review of the
Lepienski; morphology, structure and 8/1/2018; vol. 448; 30-40. abstract, the study
Kuroda; wettability of phase dependent DOI: examines a modified
Kuromoto lamellar and nanotube oxides on 10.1016/j.apsusc.2018.04.079 titanium.
anodized Ti-10Nb alloy
47 Vazquez, E.; Computer Fluid Dynamics Analysis Materials and Manufacturing After review of the
Kemmoku, D.; for Efficient Cooling and Lubrication Processes. 10/7/2014; vol. 29; abstract, the study
Noritomi, P.; da Conditions in Micromilling of 1494-1501. DOI: examines a modified
Silva, J.; Ti6Al4V Alloy 10.1080/10426914.2014.941 titanium.
Ciurana, J. 864
48 Azaouzi, M.; Deployment of a self-expanding Materials and Design. After review of the
Makradi, A.; stent inside an artery: A finite 10/2012; vol. 41; 410-420. abstract, the study
Belouettar, S. element analysis DOI: examines a modified
10.1016/j.matdes.2012.05.01 titanium.
9
49 Liang; Feng; Development of a new β Ti alloy Materials Science & After review of the
Yin; Liu; Ma; Liu with low modulus and favorable Engineering C. 4/1/2016; vol. abstract, the study
plasticity for implant material 61; 338-343. DOI: examines a modified
10.1016/j.msec.2015.12.076 titanium.
50 Archana, D.; Evaluation of chitosan nano International Journal of After review of the
Dutta, J.; Dutta, dressing for wound healing: Biological Macromolecules. abstract, the study
P.K. Characterization, in vitro and in vivo 6/2013; vol. 57; 193-203. DOI: examines a chitosan
studies 10.1016/j.ijbiomac.2013.03.00 dressing.
2
51 Elahinia; Fabrication of NiTi through additive Progress in Materials Science. Review article.
Shayesteh manufacturing: A review 10/2016; vol. 83; 630-663.
Moghaddam; DOI:
Taheri Andani; 10.1016/j.pmatsci.2016.08.00
Amerinatanzi; 1
Bimber;
Hamilton
52 Baptista; Fatigue behavior of arc melted Ti– International Journal of After review of the
Schneider; 13Nb–13Zr alloy Fatigue. 9/2004; vol. 26; 967- abstract, the study
Taddei; da Silva 973. DOI: examines a modified
10.1016/j.ijfatigue.2004.01.01 titanium.
1
53 Markhoff; Influence of different grained Materials Science & After review of the
Weinmann; powders and pellets made of Engineering C. 4/1/2017; vol. abstract, the study
Schulze; Bader

Niobium and Ti-42Nb on human 73; 756-766. DOI: examines a modified
cell viability 10.1016/j.msec.2016.12.098 titanium.
54 Garcia- Mechanical impact behavior of Composite Structures. 6/2015; After review of the
Gonzalez, D.; polyether-ether-ketone (PEEK) vol. 124; 88-99. DOI: abstract, the study
Rusinek, A.; 10.1016/j.compstruct.2014.12 examines PEEK.
Jankowiak, T.; .061
Arias, A.
55 R.; A.P.S.; R.; Metal oxide curcumin incorporated Applied Surface Science. After review of the
M.; T.; J.; polymer patches for wound healing 8/15/2018; vol. 449; 603-609. abstract, the study
Chelliah; Oh; S.; DOI: examines a modified
G. 10.1016/j.apsusc.2018.01.143 titanium.
56 Dimakos, Optimization Of The Fatigue Procedia structural integrity. After review of the
Konstantinos; Resistance Of Nitinol Stents 2016; vol. 2; 1522-1529. DOI: abstract, the study
Mariotto, Through Shot Peening 10.1016/j.prostr.2016.06.193 examines a modified
Andrea; titanium.
Giacosa,
Fausto
57 Zeller‐ Quantitative characterization of Materials and Corrosion. After review of the
Plumhoff, B.; degradation processes in situ by 3/5/2018; vol. 69; 298-306. abstract, the study
Helmholz, H.; means of a bioreactor coupled flow DOI: examines a modified
Feyerabend, F.; chamber under physiological 10.1002/maco.201709514 titanium.
Dose, T.; Wilde, conditions using time‐lapse SRµCT
F.; Hipp, A.;
Beckmann, F.;
Willumeit‐
Römer, R.;
Hammel, J.
58 Sungail; Abid Spherical tantalum feed powder for Metal Powder Report. After review of the
metal additive manufacturing 11/2018; vol. 73; 316-318. abstract, the study
DOI: examines tantalum.
10.1016/j.mprp.2018.03.046
59 Lopes, C.; TiAg"x thin films for lower limb Applied Surface Science. After review of the
Goncalves, C.; prosthesis pressure sensors: Effect 11/15/2013; vol. 285; 10-18. abstract, the study
Pedrosa, P.; of composition and structural DOI: examines a modified
Macedo, F.; changes on the electrical and 10.1016/j.apsusc.2013.07.021 titanium.
Alves, E.; thermal response of the films
Barradas, N.P.;
Martin, N.;
Fonseca, C.;
Vaz, F.
60 Oliveira; Understanding growth mechanisms Applied Surface Science. After review of the
Ribeiro; Perez; and tribocorrosion behaviour of 6/30/2015; vol. 341; 1-12. abstract, the study
Archanjo; porous TiO2 anodic films containing DOI: examines a modified
Gouvea; calcium, phosphorous and 10.1016/j.apsusc.2015.02.163 titanium.
Araújo; magnesium
Campos;
Kuznetsov;
Almeida; Maru;

Achete;
Ponthiaux;
Celis; Rocha
61 Shrestha; π-Conjugated polyaniline-assisted Chemical Engineering Journal. After review of the
Shrestha; flexible titania nanotubes with 3/15/2019; vol. 360; 701-713. abstract, the study
Baral; Lee; Kim; controlled surface morphology as DOI: examines a modified
Park; Kim regenerative medicine in nerve cell 10.1016/j.cej.2018.12.027 titanium.
growth
62 van Hengel IAJ, Self-defending additively J Mater Chem B. 2020 Feb After review of the
Tierolf MWAM, manufactured bone implants 26;8(8):1589-1602. doi: abstract, the study looks
Valerio VPM, bearing silver and copper 10.1039/c9tb02434d. PMID: at coatings on titanium
Minneboo M, nanoparticles 31848564. alloys.
Fluit AC,
Fratila-
Apachitei LE,
Apachitei I,
Zadpoor AA.
63 Guazzo R, Graphene-Based Nanomaterials Nanomaterials (Basel). 2018 After review of the
Gardin C, Bellin for Tissue Engineering in the Dental May 20;8(5):349. doi: abstract, the study
G, Sbricoli L, Field 10.3390/nano8050349. PMID: examines a modified
Ferroni L, 29783786; PMCID: titanium.
Ludovichetti PMC5977363.
FS, Piattelli A,
Antoniac I,
Bressan E,
Zavan B.
64 Wong CC, Biocompatibility and Osteogenic Interference Fixation. Int J Mol After review of the
Wong PC, Tsai Capacity of Mg-Zn-Ca Bulk Metallic Sci. 2019 May 3;20(9):2191. abstract, the study
PH, Jang JS, Glass for Rabbit Tendon-Bone doi: 10.3390/ijms20092191. examines a titanium alloy.
Cheng CK, Interference Fixation PMID: 31058825; PMCID:
Chen HH, Chen PMC6539447.
CH.
65 Choy MT, Tang In vitro and in vivo performance of Mater Sci Eng C Mater Biol After review of the
CY, Chen L, bioactive Ti6Al4V/TiC/HA implants Appl. 2014 Sep;42:746-56. abstract, the study
Wong CT, Tsui fabricated by a rapid microwave doi: examines a modified
CP. sintering technique 10.1016/j.msec.2014.06.015. titanium.
Epub 2014 Jun 20. PMID:
25063176.
66 Xu W, Lu X, Mechanical properties, in vitro J Mech Behav Biomed Mater. After review of the
Wang LN, Shi corrosion resistance and 2018 Dec;88:534-547. doi: abstract, the study
ZM, Lv SM, biocompatibility of metal injection 10.1016/j.jmbbm.2018.08.038 examines a modified
Qian M, Qu XH. molded Ti-12Mo alloy for dental . Epub 2018 Aug 28. PMID: titanium.
applications 30223215.
67 Costa BC, Vanadium ionic species from Mater Sci Eng C Mater Biol After review of the
Tokuhara CK, degradation of Ti-6Al-4V metallic Appl. 2019 Mar;96:730-739. abstract, the study
Rocha LA, implants: In vitro cytotoxicity and doi: examines a titanium alloy.
Oliveira RC, speciation evaluation 10.1016/j.msec.2018.11.090.
Lisboa-Filho

PN, Costa Epub 2018 Dec 2. PMID:
Pessoa J. 30606586.
68 Sidambe AT. Biocompatibility of Advanced Materials (Basel). 2014 Dec Review article.
Manufactured Titanium Implants-A 19;7(12):8168-8188. doi:
Review 10.3390/ma7128168. PMID:
28788296; PMCID:
PMC5456424.
69 Li L, Bai W, Mechanical Properties and in Vitro ACS Appl Mater Interfaces. After review of the
Wang X, Gu C, and in Vivo Biocompatibility of a- 2017 May 17;9(19):15933- abstract, the study
Jin G, Tu J. C/a-C:Ti Nanomultilayer Films on 15942. doi: examines a titanium alloy.
Ti6Al4V Alloy as Medical Implants 10.1021/acsami.7b02552.
Epub 2017 May 8. PMID:
28467042.
70 Wang YB, Li In vitro and in vivo studies on Ti- Mater Sci Eng C Mater Biol After review of the
HF, Cheng Y, based bulk metallic glass as Appl. 2013 Aug 1;33(6):3489- abstract, the study
Zheng YF, potential dental implant material 97. doi: examines a modified
Ruan LQ. 10.1016/j.msec.2013.04.038. titanium.
Epub 2013 Apr 25. PMID:
23706238.
71 Chellini F, Mesenchymal stromal cell and Lasers Med Sci. 2017 After review of the
Giannelli M, osteoblast responses to oxidized Aug;32(6):1309-1320. doi: abstract, the study
Tani A, Ballerini titanium surfaces pre-treated with 10.1007/s10103-017-2243-5. examines a modified
L, Vallone L, λ = 808 nm GaAlAs diode laser or Epub 2017 May 27. PMID: titanium.
Nosi D, Zecchi- chlorhexidine: in vitro study 28551763.
Orlandini S,
Sassoli C.
72 Singhatanadgit Titanium dioxide nanotubes of J Biomater Appl. 2019 After review of the
W, Toso M, defined diameter enhance Feb;33(7):997-1010. doi: abstract, the study
Pratheepsawan mesenchymal stem cell 10.1177/0885328218816565. examines a modified
gwong B, proliferation via JNK- and ERK- Epub 2018 Dec 5. PMID: titanium.
Pimpin A, dependent up-regulation of 30757966.
Srituravanich fibroblast growth factor-2 by T
W. lymphocytes
73 Vasilescu E, In vitro biocompatibility and J Mater Sci Mater Med. 2010 After review of the
Drob P, corrosion resistance of a new Jun;21(6):1959-68. doi: abstract, the study
Raducanu D, implant titanium base alloy 10.1007/s10856-010-4057-x. examines a modified
Cojocaru VD, Epub 2010 Mar 25. PMID: titanium.
Cinca I, 20336353.
Iordachescu D,
Ion R, Popa M,
Vasilescu C.
74 Citeau A, In vitro biological effects of titanium Biomaterials. 2005 After review of the
Guicheux J, rough surface obtained by calcium Jan;26(2):157-65. doi: abstract, the study
Vinatier C, phosphate grid blasting 10.1016/j.biomaterials.2004.0 examines a titanium alloy.
Layrolle P, 2.033. PMID: 15207462.
Nguyen TP,
Pilet P, Daculsi
G.

75 Mohanapriya S, Fabrication and characterization of J Mech Behav Biomed Mater. After review of the
Mumjitha M, poly(vinyl alcohol)-TiO2 2016 Oct;63:141-156. doi: abstract, the study
PurnaSai K, Raj nanocomposite films for orthopedic 10.1016/j.jmbbm.2016.06.009 examines a modified
V. applications . Epub 2016 Jun 14. PMID: titanium.
27371870.
76 Mondal D, Microstructure and biocompatibility J Biomed Mater Res A. 2013 After review of the
Nguyen L, Oh of composite biomaterials May;101(5):1489-501. doi: abstract, the study
IH, Lee BT. fabricated from titanium and 10.1002/jbm.a.34455. Epub examines a modified
tricalcium phosphate by spark 2012 Nov 7. PMID: 23135893. titanium.
plasma sintering
77 Marchi J, Ussui Analysis in vitro of the cytotoxicity J Biomed Mater Res B Appl After review of the
V, Delfino CS, of potential implant materials. I: Biomater. 2010 abstract, the study
Bressiani AH, Zirconia-titania sintered ceramics Aug;94(2):305-11. doi: examines a modified
Marques MM. 10.1002/jbm.b.31652. PMID: titanium.
20586079.
78 Assad M, A new porous titanium-nickel alloy: Biomed Mater Eng. After review of the
Chernyshov A, Part 1. Cytotoxicity and 2002;12(3):225-37. PMID: abstract, the study
Leroux MA, genotoxicity evaluation 12446938. examines a modified
Rivard CH. titanium.
79 Ezechieli M, Biodegradation of a magnesium J Biomater Appl. 2014 After review of the
Diekmann J, alloy implant in the intercondylar Aug;29(2):291-302. doi: abstract, the study
Weizbauer A, femoral notch showed an 10.1177/0885328214523322. examines a modified
Becher C, appropriate response to the Epub 2014 Feb 12. PMID: titanium.
Willbold E, synovial membrane in a rabbit 24522242.
Helmecke P, model in vivo
Lucas A,
Schavan R,
Windhagen H.
80 Assis SL, A comparative study of the in vitro J Biomed Mater Res B Appl After review of the
Rogero SO, corrosion behavior and cytotoxicity Biomater. 2005 abstract, the study
Antunes RA, of a superferritic stainless steel, a Apr;73(1):109-16. doi: examines a modified
Padilha AF, Ti-13Nb-13Zr alloy, and an 10.1002/jbm.b.30205. PMID: titanium.
Costa I. austenitic stainless steel in Hank's 15660438.
solution
81 Sabetrasekh R, Impact of trace elements on Biomed Mater. 2010 After review of the
Tiainen H, biocompatibility of titanium Feb;5(1):15003. doi: abstract, the study
Reseland JE, scaffolds 10.1088/1748- examines titanium dioxide
Will J, Ellingsen 6041/5/1/015003. Epub 2010 powders.
JE, Lyngstadaas Jan 7. PMID: 20057018.
SP, Haugen HJ.
82 Bello SA, de In vitro evaluation of human J Mater Sci Mater Med. 2010 After review of the
Jesús- osteoblast adhesion to a thermally May;21(5):1739-50. doi: abstract, the study
Maldonado I, oxidized gamma-TiAl intermetallic 10.1007/s10856-010-4016-6. examines a modified
Rosim-Fachini alloy of composition Ti-48Al-2Cr- Epub 2010 Feb 17. PMID: titanium.
E, Sundaram 2Nb (at.%) 20162332; PMCID:
PA, Diffoot- PMC2871339.
Carlo N.

83 Park CH, Lee Improved pre-osteoblast response Clin Oral Implants Res. 2011 After review of the
CS, Kim YJ, Jang and mechanical compatibility of Jul;22(7):735-742. doi: abstract, the study
JH, Suh JY, Park ultrafine-grained Ti-13Nb-13Zr 10.1111/j.1600- examines a modified
JW. alloy 0501.2010.02053.x. Epub titanium.
2010 Dec 2. PMID: 21121961.
84 van Hengel IAJ, Antibacterial Titanium Implants Int J Mol Sci. 2021 Apr Review article.
Tierolf MWAM, Biofunctionalized by Plasma 6;22(7):3800. doi:
Fratila- Electrolytic Oxidation with Silver, 10.3390/ijms22073800. PMID:
Apachitei LE, Zinc, and Copper: A Systematic 33917615; PMCID:
Apachitei I, Review PMC8038786.
Zadpoor AA.
85 Assad M, A new porous titanium-nickel alloy: Biomed Mater Eng. After review of the
Chernyshov A, part 2. Sensitization, irritation and 2002;12(4):339-46. PMID: abstract, the study
Leroux MA, acute systemic toxicity evaluation 12652028. examines a modified
Rivard CH. titanium.
86 Yu SR, Zhang Effects of Ce on the short-term J Mater Sci Mater Med. 2004 After review of the
XP, He ZM, Liu biocompatibility of Ti-Fe-Mo-Mn- Jun;15(6):687-91. doi: abstract, the study
YH, Liu ZH. Nb-Zr alloy for dental materials 10.1023/b:jmsm.0000030210 examines a modified
.83891.d4. PMID: 15346736. titanium.
87 Fage SW, Muris Titanium: a review on exposure, Contact Dermatitis. 2016 Review article.
J, Jakobsen SS, release, penetration, allergy, Jun;74(6):323-45. doi:
Thyssen JP. epidemiology, and clinical reactivity 10.1111/cod.12565. Epub
2016 Mar 29. PMID:
27027398.
88 Kim KT, Eo MY, General review of titanium toxicity Int J Implant Dent. 2019 Mar Review article.
Nguyen TTH, 11;5(1):10. doi:
Kim SM. 10.1186/s40729-019-0162-x.
PMID: 30854575; PMCID:
PMC6409289.
89 Syed M, Allergic Reactions to Dental J Clin Diagn Res. 2015 Review article.
Chopra R, Materials-A Systematic Review Oct;9(10):ZE04-9. doi:
Sachdev V. 10.7860/JCDR/2015/15640.6
589. Epub 2015 Oct 1. PMID:
26557634; PMCID:
PMC4625353.
90 Mombelli A, What is the impact of titanium Clin Oral Implants Res. 2018 Review article.
Hashim D, particles and biocorrosion on Oct;29 Suppl 18:37-53. doi:
Cionca N. implant survival and complications? 10.1111/clr.13305. PMID:
A critical review 30306693.
91 Comino- Allergies to Titanium Dental Biology (Basel). 2020 Nov Review article.
Garayoa R, Implants: What Do We Really Know 18;9(11):404. doi:
Cortés-Bretón about Them? A Scoping Review 10.3390/biology9110404.
Brinkmann J, PMID: 33217944; PMCID:
Peláez J, López- PMC7698636.
Suárez C,
Martínez-
González JM,
Suárez MJ.

92 Shi C, Xi Y, Sun Suspected allergy to titanium after Br J Neurosurg. 2020 Jan 31:1- After review of the
B, He H, Wen J, anterior cervical discectomy and 5. doi: abstract, the study
Ruan Y, Ye X. fusion using a Zero-P device: a case 10.1080/02688697.2020.171 examines a case report.
report 8605. Epub ahead of print.
PMID: 32003246.
93 Siddiqi A, Titanium allergy: could it affect Clin Oral Implants Res. 2011 Review article.
Payne AGT, De dental implant integration? Jul;22(7):673-680. doi:
Silva RK, 10.1111/j.1600-
Duncan WJ. 0501.2010.02081.x. Epub
2011 Jan 20. PMID: 21251079.
94 Desai MM, Prevalence of metal J Orthop. 2019 May After review of the
Shah KA, hypersensitivity in total knee 28;16(6):468-472. doi: abstract, the study
Mohapatra A, replacement 10.1016/j.jor.2019.05.005. examines allergies in other
Patel DC. PMID: 31680733; PMCID: metals.
PMC6818373.
95 Bjørklund G, Delayed-type hypersensitivity to Environ Res. 2018 After review of the
Dadar M, metals in connective tissue diseases Feb;161:573-579. doi: abstract, the study
Aaseth J. and fibromyalgia 10.1016/j.envres.2017.12.004 examines connective
. PMID: 29245125. tissue diseases.
96 Razzante MC, Type IV Cell-Mediated J Foot Ankle Surg. 2019 Review article.
Ehredt DJ, Hypersensitivity Reaction Caused Sep;58(5):974-979. doi:
Clougherty CO, by Titanium Implant Following 10.1053/j.jfas.2018.11.031.
Kriger SJ, Double Calcaneal Osteotomy and Epub 2019 Jun 29. PMID:
Menninger BA, First Metatarsal-Cuneiform 31266695.
Behan Arthrodesis: A Case Report and
Dionisopoulos Review of the Literature
S, Bhakta PJ,
Bruning NG.
97 Cousen PJ, Metal allergy and second- Contact Dermatitis. 2012 After review of the
Gawkrodger DJ. generation metal-on-metal Feb;66(2):55-62. doi: abstract, the study
arthroplasties 10.1111/j.1600- examines a titanium alloy.
0536.2011.01970.x. Epub
2011 Sep 29. PMID:
21957973.
98 Henry A, Revision temporomandibular joint Int J Oral Maxillofac Surg. 2020 After review of the
Inverso G, arthroplasty for the treatment of Mar;49(3):356-360. doi: abstract, the study
Granquist EJ. acquired metal allergy and review 10.1016/j.ijom.2019.08.002. examines a titanium alloy.
of the literature Epub 2019 Aug 23. PMID:
31447220.
99 D'Ambrosi R, Titanium Niobium Nitride Mobile- J Arthroplasty. 2021 After review of the
Nuara A, Bearing Unicompartmental Knee Jan;36(1):140-147.e2. doi: abstract, the study
Mariani I, Di Arthroplasty Results in Good to 10.1016/j.arth.2020.07.028. examines a modified
Feo F, Ursino Excellent Clinical and Radiographic Epub 2020 Jul 21. PMID: titanium.
N, Hirschmann Outcomes in Metal Allergy Patients 32773267.
M. With Medial Knee Osteoarthritis
100 Bouguennec N, The Migratory Cortical Button: A Knee Surg Relat Res. 2019 Jun Case study.
Colombet P, Rare Case of Hypersensitivity to 1;31(2):132-136. doi:
10.5792/ksrr.18.072. PMID:

Graveleau N, Titanium after an Anterior Cruciate 30893989; PMCID:
Jambou S. Ligament Reconstruction PMC6561671.
101 Towers WS, Rare Systemic Response to Cureus. 2020 Feb Case study.
Kurtom K. Titanium Spinal Fusion Implant: 26;12(2):e7109. doi:
Case Report 10.7759/cureus.7109. PMID:
32257657; PMCID:
PMC7100857.
102 Wang LF, Wu J, Long-Term Fever After Hallux J Foot Ankle Surg. 2016 Nov- Case study.
Zheng C, Li SL, Valgus Surgery Secondary to Dec;55(6):1282-1286. doi:
Huang RR, Titanium Allergy: A Case Report 10.1053/j.jfas.2015.06.021.
Zhang JK. and Review of the Literature Epub 2015 Jul 30. PMID:
26234925.
103 Rahilly G, Price 9. Nickel allergy and J Orthod. 2003 Jun;30(2):171- After review of the
N. orthodontics 4. doi: abstract, the study
10.1093/ortho/30.2.171. examines nickel allergies.
PMID: 12835436.
104 Dmochowski Could a Titanium Ulnar Shortening J Wrist Surg. 2019 Case study.
JM, Royal JT, Plate Trigger a Metal Allergy? A Dec;8(6):503-507. doi:
Lourie GM. Case Report 10.1055/s-0039-1677742.
Epub 2019 Feb 1. PMID:
31815066; PMCID:
PMC6892651.
105 Ohkubo C, Present status of titanium J Oral Rehabil. 2008 Review article.
Hanatani S, removable dentures--a review of Sep;35(9):706-14. doi:
Hosoi T. the literature 10.1111/j.1365-
2842.2007.01821.x. PMID:
18793355.
106 Univers J, Long Systemic hypersensitivity reaction J Vasc Surg. 2018 Case study.
C, Tonks SA, to endovascular stainless steel Feb;67(2):615-617. doi:
Freeman MB. stent 10.1016/j.jvs.2017.08.085.
Epub 2017 Dec 13. PMID:
29248243.
107 Thomas P, Hypersensitivity to titanium Contact Dermatitis. 2006 Case study.
Bandl WD, osteosynthesis with impaired Oct;55(4):199-202. doi:
Maier S, fracture healing, eczema, and T- 10.1111/j.1600-
Summer B, cell hyperresponsiveness in vitro: 0536.2006.00931.x. PMID:
Przybilla B. case report and review of the 16958916.
literature
108 Tawil G, Tawil Zirconium Implant as an Alternative Int J Oral Maxillofac Implants. Case study.
P, Irani C. to Titanium Implant in a Case of 2020 May/Jun;35(3):639-644.
Type IV Titanium Allergy: Case doi: 10.11607/jomi.7990.
Report PMID: 32406664.
109 Schreiver I, Distribution of nickel and chromium Part Fibre Toxicol. 2019 Aug After review of the
Hesse B, Seim containing particles from tattoo 27;16(1):33. doi: abstract, the study
C, Castillo- needle wear in humans and its 10.1186/s12989-019-0317-1. examines nickel allergies.
Michel H, possible impact on allergic PMID: 31451117; PMCID:
Anklamm L, reactions PMC6710876.
Villanova J,

Dreiack N,
Lagrange A,
Penning R, De
Cuyper C,
Tucoulou R,
Bäumler W,
Cotte M, Luch
A.
110 Andrei OC, Suspicions of titanium allergic Rom J Morphol Embryol. Case study.
Tănăsescu LA, reaction influencing the prosthetic 2019;60(1):233-241. PMID:
Burlibaşa M, solution in a rare case of implant 31263850.
Bătăiosu M, "flowering"
Dăguci L,
Burlibaşa L,
Turcu AA,
Dăguci C.
111 Pigatto PD, Fever of Unknown Origin, Allergy J Foot Ankle Surg. 2016 Sep- Case study.
Brambilla L, to Titanium, and Hallux Valgus Oct;55(5):1128. doi:
Ferrucci S, Surgery 10.1053/j.jfas.2016.04.002.
Guzzi G. Epub 2016 Jun 7. PMID:
27286925.
112 Goto M, Gotoh Hypersensitivity to suture anchors Case Rep Orthop. Case study.
M, Mitsui Y, 2013;2013:932167. doi:
Tanesue R, 10.1155/2013/932167. Epub
Okawa T, 2013 Jul 11. PMID: 23956902;
Higuchi F, PMCID: PMC3728555.
Shiba N.
113 Rossi SMP, Ten-year outcomes of a nitrided Ti- Knee. 2020 Oct;27(5):1519- After review of the
Perticarini L, 6Al-4V titanium alloy fixed-bearing 1524. doi: abstract, the study
Mosconi M, total knee replacement with a 10.1016/j.knee.2020.08.007. examines a modified
Ghiara M, highly crosslinked polyethylene- Epub 2020 Aug 27. PMID: titanium.
Benazzo F. bearing in patients with metal 33010769.
allergy
114 Saha BK, Modi Asthma From Allergy to Titanium in Ann Intern Med. 2020 Jun Case study.
A, Beegle S. a Cardiac Pacemaker 16;172(12):837-838. doi:
10.7326/L19-0647. Epub
2020 Mar 31. PMID:
32227246.
115 Noble J, Ahing Nickel allergy and orthodontics, a Br Dent J. 2008 Mar Case study.
SI, Karaiskos review and report of two cases 22;204(6):297-300. doi:
NE, Wiltshire 10.1038/bdj.2008.198. PMID:
WA. 18356874.
116 Obermeyer RJ, Selective versus routine patch J Pediatr Surg. 2018 After review of the
Gaffar S, Kelly metal allergy testing to select bar Feb;53(2):260-264. doi: abstract, the study
RE Jr, Kuhn MA, material for the Nuss procedure in 10.1016/j.jpedsurg.2017.11.02 examines stainless steels.
Frantz FW, 932 patients over 10years 1. Epub 2017 Nov 14. PMID:
McGuire MM, 29223667.

Paulson JF,
Kelly CS.
117 Javed F, Al- Is titanium sensitivity associated Clin Implant Dent Relat Res. Review article.
Hezaimi K, with allergic reactions in patients 2013 Feb;15(1):47-52. doi:
Almas K, with dental implants? A systematic 10.1111/j.1708-
Romanos GE. review 8208.2010.00330.x. Epub
2011 Mar 17. PMID:
21414135.
118 Hosoki M, Allergic contact dermatitis caused J Prosthodont Res. 2016 Case study.
Nishigawa K, by titanium screws and dental Jul;60(3):213-9. doi:
Miyamoto Y, implants 10.1016/j.jpor.2015.12.004.
Ohe G, Epub 2016 Jan 8. PMID:
Matsuka Y. 26774509.
119 Schalock PC, Metal hypersensitivity reactions to Dermatitis. 2013 Nov- After review of the
Thyssen JP. implants: opinions and practices of Dec;24(6):313-20. doi: abstract, the study
patch testing dermatologists 10.1097/DER.0b013e3182a6 examines patch testing
7d90. PMID: 24201465. methods.
120 Shah B, Cohee High rates of metal allergy J Pediatr Surg. 2014 After review of the
A, Deyerle A, amongst Nuss procedure patients Mar;49(3):451-4. doi: abstract, the study
Kelly CS, Frantz dictate broader pre-operative 10.1016/j.jpedsurg.2013.07.0 examines metal allergies.
F, Kelly RE, testing 14. PMID: 24650476.
Kuhn MA,
Lombardo M,
Obermeyer R,
Goretsky MJ.
121 Forte G, Metal allergens of growing Inflamm Allergy Drug Targets. Review article.
Petrucci F, significance: epidemiology, 2008 Sep;7(3):145-62. doi:
Bocca B. immunotoxicology, strategies for 10.2174/1871528087857481
testing and prevention 46. PMID: 18782021.
122 de Cuyper C, Are metals involved in tattoo- Contact Dermatitis. 2017 Case study.
Lodewick E, related hypersensitivity reactions? Dec;77(6):397-405. doi:
Schreiver I, A case report 10.1111/cod.12862. Epub
Hesse B, Seim 2017 Aug 9. PMID: 28795428.
C, Castillo-
Michel H, Laux
P, Luch A.
123 Dawson- Adverse Reaction to Zirconia in a Arthroplast Today. 2020 Jun Case study.
Amoah KG, Modern Total Hip Arthroplasty with 19;6(3):612-616.e1. doi:
Waddell BS, Ceramic Head 10.1016/j.artd.2020.03.009.
Prakash R, PMID: 32995410; PMCID:
Alexiades MM. PMC7502561.
124 Stejskal V, Increased frequency of delayed J Trace Elem Med Biol. After review of the
Reynolds T, type hypersensitivity to metals in 2015;31:230-6. doi: abstract, the study
Bjørklund G. patients with connective tissue 10.1016/j.jtemb.2015.01.001. examines patients with
disease Epub 2015 Jan 14. PMID: connective tissue disease.
25636536.

125 Goodwin ML, Failure of facet replacement J Neurosurg Spine. 2018 Case study.
Spiker WR, system with metal-on-metal Jul;29(1):81-84. doi:
Brodke DS, bearing surface and subsequent 10.3171/2017.10.SPINE1786
Lawrence BD. discovery of cobalt allergy: report 2. Epub 2018 Apr 13. PMID:
of 2 cases 29652237.
126 Kolokitha OE, A severe reaction to ni-containing Angle Orthod. 2009 After review of the
Chatzistavrou orthodontic appliances Jan;79(1):186-92. doi: abstract, the study
E. 10.2319/111507-531.1. PMID: examines nickel allergies.
19123714.
127 Ko N, Mine A, Allergic reaction to titanium-made J Prosthodont. 2014 Case study.
Egusa H, fixed dental restorations: A clinical Aug;23(6):501-3. doi:
Shimazu T, Ko report 10.1111/jopr.12136. PMID:
R, Nakano T, 27588324.
Yatani H.
128 Granchi D, Sensitivity to implant materials in Biomaterials. 2008 After review of the
Cenni E, Tigani patients with total knee Apr;29(10):1494-500. doi: abstract, the study
D, Trisolino G, arthroplasties 10.1016/j.biomaterials.2007.1 examines a modified
Baldini N, 1.038. Epub 2007 Dec 21. titanium.
Giunti A. PMID: 18155140.
129 Kono T, Oda T, Remission of Palmoplantar Ann Thorac Cardiovasc Surg. Case study.
Akaiwa K, Pustulosis after On-Pump Coronary 2020 Jun 20;26(3):170-173.
Nakamura K, Artery Bypass Grafting in a Patient doi: 10.5761/atcs.cr.18-
Sasaoka K, with Titanium Allergy 00031. Epub 2018 Apr 20.
Tanaka H. PMID: 29681595; PMCID:
PMC7303315.
130 de Haar C, Ultrafine but not fine particulate Clin Exp Allergy. 2006 After review of the
Hassing I, Bol matter causes airway inflammation Nov;36(11):1469-79. doi: abstract, the study
M, Bleumink R, and allergic airway sensitization to 10.1111/j.1365- examines a modified
Pieters R. co-administered antigen in mice 2222.2006.02586.x. PMID: titanium.
17083358.
131 D'Ambrosi R, Similar rates of return to sports and Knee Surg Sports Traumatol After review of the
Anghilieri FM, BMI reduction regardless of age, Arthrosc. 2021 Feb 7. doi: abstract, the study
Corona K, gender and preoperative BMI as 10.1007/s00167-021-06467- examines a modified
Mariani I, Valli seen in matched cohort of 1. Epub ahead of print. PMID: titanium.
F, Ursino N, hypoallergenic and standard Cobalt 33550449.
Hirschmann Chromium medial
MT. unicompartmental knee
arthroplasty
132 Yan H, Afroz S, Metal allergy patient treated by Clin Case Rep. 2018 Aug Case study.
Dalanon J, Goto titanium implant denture: A case 28;6(10):1972-1977. doi:
N, Hosoki M, report with at least 4-year follow- 10.1002/ccr3.1753. PMID:
Matsuka Y. up 30349710; PMCID:
PMC6186882.
133 Volkman KK, Adverse reactions to orthodontic Allergy Asthma Proc. 2007 Jul- After review of the
Inda MJ, Reichl appliances in nickel-allergic patients Aug;28(4):480-4. doi: abstract, the study
PG, Zacharisen 10.2500/aap.2007.28.3018. examines a modified
MC. PMID: 17883919. titanium.

134 Sakamoto K, Metal allergy to titanium bars after Ann Thorac Surg. 2014 Case study.
Ando K, Noma the Nuss procedure for pectus Aug;98(2):708-10. doi:
D. excavatum 10.1016/j.athoracsur.2013.10.
089. PMID: 25087797.
135 Navratil M, Metal allergy as a late-onset Pediatr Pulmonol. 2018 Case study.
Batinica M, complication of the Nuss procedure Aug;53(8):E24-E26. doi:
Ivković- in a pediatric patient 10.1002/ppul.24072. Epub
Jureković I. 2018 Jun 13. PMID: 29897675.
136 Szema AM, Jo A plane screw fixation is a nidus IDCases. 2017 Apr 26;8:96- Case study.
C. for Paecilomyces sinusitis in a 100. doi:
patient with aspirin exacerbated 10.1016/j.idcr.2017.04.002.
respiratory disease PMID: 28516039; PMCID:
PMC5430495.
137 Heitmiller K, Diagnostic dilemmas of Titanium Eur Ann Allergy Clin Immunol. Case study.
Innes M, Zollo Hypersensitivity in patients with 2021 Jan;53(1):43-46. doi:
V, Sansur C, medical implants: a case series 10.23822/EurAnnACI.1764-
Goldner R, 1489.141. Epub 2021 Jan 7.
Powell D, PMID: 32378396.
Gaspari AA.
138 Brahimaj B, Iodine-125 seed migration within J Neurosurg. 2016 Case study.
Lamba M, brain parenchyma after Nov;125(5):1167-1170. doi:
Breneman JC, brachytherapy for brain metastasis: 10.3171/2015.11.JNS151464.
Warnick RE. case report Epub 2016 Feb 26. PMID:
26918472.
139 Franzen DP, Evaluation of Nickel Release from Int Arch Allergy Immunol. After review of the
Lang C, Endobronchial Valves as a Possible 2017;174(3-4):144-150. doi: abstract, the study
Agorastos N, Cause of Hypersensitivity 10.1159/000481986. Epub examines nickel allergies.
Freitag L, Pneumonitis in a Patient Treated 2017 Nov 15. PMID:
Kohler M, with Bronchoscopic Lung Volume 29136621.
Schmid- Reduction
Grendelmeier
P.
140 Niiyama S, Th2 immune response plays a Int Arch Allergy Immunol. After review of the
Tamauchi H, critical role in the development of 2010;153(3):303-14. doi: abstract, the study
Amoh Y, nickel-induced allergic contact 10.1159/000314372. Epub examines a modified
Terashima M, dermatitis 2010 May 20. PMID: titanium.
Matsumura Y, 20484930.
Kanoh M, Habu
S, Komotori J,
Katsuoka K.
141 Dietrich KA, Intolerance reactions to knee J Dtsch Dermatol Ges. 2009 After review of the
Mazoochian F, arthroplasty in patients with May;7(5):410-3. English, abstract, the study
Summer B, nickel/cobalt allergy and German. doi: 10.1111/j.1610- examines a nickel/cobalt
Reinert M, disappearance of symptoms after 0387.2008.06987.x. Epub allergy.
Ruzicka T, revision surgery with titanium- 2009 Jan 15. PMID: 19192161.
Thomas P. based endoprostheses

142 Ross IB, Cell-mediated allergy to a cerebral Neurosurgery. 1998 Case study.
Warrington RJ, aneurysm clip: case report Nov;43(5):1209-11. doi:
Halliday WC. 10.1097/00006123-
199811000-00110. PMID:
9802865.
143 Jain MS, Delayed Titanium Hypersensitivity Case Rep Surg. 2021 Mar After review of the
Lingarajah S, and Retained Foreign Body 2;2021:5515401. doi: abstract, the study
Luvsannyam E, Causing Late Abdominal 10.1155/2021/5515401. examines a modified
Somagutta MR, Complications PMID: 33763279; PMCID: titanium.
Jagani RP, PMC7946486.
Sanni J, Ebose
E, Tiesenga FM,
Jorge JM.
144 Kim HJ, Shin JU, Positive reactions to nickel on a Dermatology. Case study.
Lee J, Lee H, Jin patch test do not predict clinical 2015;230(2):184-8. doi:
S, Kim SH, Noh outcome of nickel alloy-based atrial 10.1159/000371511. Epub
JY, Lee KH. septal defect occluder implantation 2015 Jan 23. PMID: 25634825.
145 Haraguchi S, Treatment of adult Class II division Angle Orthod. 2014 Case study.
Yamashiro T. 2 patient with metal Sep;84(5):902-9. doi:
hypersensitivity 10.2319/100613-736.1. Epub
2014 Apr 15. PMID:
24731064.
146 Oluwajana F, Titanium alloy removable partial Br Dent J. 2012 Case study.
Walmsley AD. denture framework in a patient Aug;213(3):123-4. doi:
with a metal allergy: a case study 10.1038/sj.bdj.2012.667.
PMID: 22878308.
147 Alqahtani AR, A Clinical Case Report of a Case Rep Dent. 2021 Apr Case study.
Gufran K, Silva Potential Acute Allergic Reaction 10;2021:5592934. doi:
F, Rocha MG, with Titanium Dental Implant 10.1155/2021/5592934.
Chang J. PMID: 33953988; PMCID:
PMC8057912.
148 Piozzi R, Ribeiro Genotoxicity and cytotoxicity in J Biomed Mater Res A. 2009 After review of the
DA, Padovan multiple organs induced by titanium Feb;88(2):342-7. doi: document, this study
LE, Nary Filho miniplates in Wistar rats 10.1002/jbm.a.31876. PMID: examines a titanium alloy.
H, Matsumoto 18286617.
MA.
149 Tuomi JT, In vitro cytotoxicity and surface J Mater Sci Mater Med. 2017 After review of the
Björkstrand RV, topography evaluation of additive Mar;28(3):53. doi: document, this study
Pernu ML, manufacturing titanium implant 10.1007/s10856-017-5863-1. examines titanium alloys.
Salmi MV, materials Epub 2017 Feb 14. PMID:
Huotilainen EI, 28197824.
Wolff JE, Vallittu
PK, Mäkitie AA.
150 Tamayo JA, Additive manufacturing of Ti6Al4V Heliyon. 2021 May After review of the
Riascos M, alloy via electron beam melting for 7;7(5):e06892. doi: document, this is a review
Vargas CA, the development of implants for 10.1016/j.heliyon.2021.e0689 article.
Baena LM. the biomedical industry 2. PMID: 34027149; PMCID:
PMC8120950.

151 Sun Y, Hu Y, Association between metal J Neurosurg. 2018 Jul After review of the
Yuan Q, Yu J, hypersensitivity and implant failure 6;131(1):40-46. doi: document, this study
Wu X, Du Z, Wu in patients who underwent titanium 10.3171/2018.1.JNS171804. examines routine patch
X, Hu J. cranioplasty PMID: 29979123. testing for metal allergies.
152 Straumal, B. B.; β-Ti-Based Alloys for Medical Russian Journal of Non- After review of the
Gornakova, A. Applications Ferrous Metals. 1/1/2021; vol. document, this study looks
S.; Kilmametov, 62; 54-63. DOI: at a modified titanium.
A. R.; Rabkin, 10.3103/S106782122101015
E.; Anisimova, 6
N. Yu.;
Kiselevskiy, M.
V.
153 Sidebottom AJ, Prospective analysis of the Br J Oral Maxillofac Surg. 2014 After review of the
Mistry K. incidence of metal allergy in Jan;52(1):85-6. doi: document, this is a review
patients listed for total replacement 10.1016/j.bjoms.2013.06.009. article.
of the temporomandibular joint Epub 2013 Jul 10. PMID:
23850381.
154 Schaeske J, Cell Type-Specific Adhesion and Int J Mol Sci. 2020 Nov After review of the
Fadeeva E, Migration on Laser-Structured 10;21(22):8442. doi: document, this study looks
Schlie-Wolter S, Opaque Surfaces 10.3390/ijms21228442. PMID: at screenings.
Deiwick A, 33182746; PMCID:
Chichkov BN, PMC7696563.
Ingendoh-
Tsakmakidis A,
Stiesch M,
Winkel A.
155 Rushing GD, When it is not an infection: metal J Pediatr Surg. 2007 After review of the
Goretsky MJ, allergy after the Nuss procedure for Jan;42(1):93-7. doi: document, this is a review.
Gustin T, repair of pectus excavatum 10.1016/j.jpedsurg.2006.09.0
Morales M, 56. PMID: 17208547.
Kelly RE Jr,
Nuss D.
156 Ribeiro, A perspective on molybdenum Journal of Materials Science. After review of the
Andreza; biocompatibility and antimicrobial 3/2016; vol. 51; 2806-2816. document, this is a review.
Flores- activity for applications in implants DOI: 10.1007/s10853-015-
Sahagun, 9664-y
Thais; Paredes,
Ramon
157 Ratna Sunil, B.; Nano and ultra fine grained Materials Technology. After review of the
Thirugnanam, metallic biomaterials by severe 11/9/2016; vol. 31; 743-755. document, this study looks
A.; Chakkingal, plastic deformation techniques DOI: at a modified titanium.
Uday; Sampath 10.1080/10667857.2016.124
Kumar, T. S. 9133
158 Pigatto PD, Titanium allergy associated with Clin Oral Implants Res. 2009 After review of the
Guzzi G, dental implant failure Aug;20(8):857. doi: document, this is a letter
Brambilla L, 10.1111/j.1600- to the editor.
Sforza C. 0501.2009.01749.x. PMID:
19604283.

159 Pellengahr C, Resurfacing knee arthroplasty in Arch Orthop Trauma Surg. After review of the
Mayer W, Maier patients with allergic sensitivity to 2003 May;123(4):139-43. doi: document, this study looks
M, Müller PE, metals 10.1007/s00402-002-0429-0. at a CoCrNi alloy.
Schulz C, Dürr Epub 2003 Apr 10. PMID:
HR, Trouillier H, 12687388.
Steinborn M,
Jansson V,
Refior HJ.
160 Pandurangan In Vitro Therapeutic Potential of Biol Trace Elem Res. 2016 After review of the
M, Enkhtaivan Tio2 Nanoparticles Against Human Jun;171(2):293-300. doi: document, this study looks
G, Young JA, Cervical Carcinoma Cells 10.1007/s12011-015-0551-9. at titanium dioxide.
Hoon HJ, Lee Epub 2015 Oct 31. PMID:
H, Lee S, Kim 26519422.
DH.
161 Pacheco KA. Allergy to Surgical Implants Clin Rev Allergy Immunol. After review of the
2019 Feb;56(1):72-85. doi: document, this study looks
10.1007/s12016-018-8707-y. at modified titanium.
PMID: 30220068.
162 Ou P, Hao C, Evaluation of biocompatibility and Biomed Mater. 2020 Dec 9. After review of the
Liu J, He R, osseointegration of Nb-xTi-Zr doi: 10.1088/1748- document, this study looks
Zhang T, Wang alloys for use as dental implant 605X/abd1f8. Epub ahead of at NTZ alloys.
Y, Yang H, materials print. PMID: 33296892.
Ruan J.
163 Nezhad; Qu; Effects of titanium and carbon Applied Surface Science. After review of the
Musharavati; nanotubes on 2/1/2021; vol. 538. DOI: document, this study looks
Jaber; nano/micromechanical properties 10.1016/j.apsusc.2020.14812 at composites.
Appleford; Bae; of HA/TNT/CNT nanocomposites 3
Uzun;
Struthers;
Chowdhury;
Khandakar
164 Nakazawa G, Sirolimus-eluting stents suppress Circ J. 2008 Jun;72(6):893-6. After review of the
Tanabe K, Aoki neointimal formation irrespective of doi: 10.1253/circj.72.893. document, this study looks
J, Onuma Y, metallic allergy PMID: 18503212. at metallic allergies and
Higashikuni Y, angiographic outcomes
Yamamoto H, after SES implantation.
Ohtsuki S,
Yachi S,
Yagishita A,
Nakajima H,
Hara K.
165 Maspero C, Titanium orthodontic appliances for Minerva Stomatol. 2014 Nov- After review of the
Giannini L, allergic patients Dec;63(11-12):403-10. PMID: abstract, the study looks
Galbiati G, 25503341. at allergy to resin and
Nolet F, nickel.
Esposito L,
Farronato G.

166 Maspero C, Titanium TSME appliance for Eur J Paediatr Dent. 2018 After review of the
Galbiati G, patients allergic to nickel Mar;19(1):67-69. doi: document, this study looks
Giannini L, 10.23804/ejpd.2018.19.01.12. at allergy to resin and
Guenza G, PMID: 29569457 nickel.
Esposito L,
Farronato G.
167 Lons A, Metallic ion release after knee Int Orthop. 2017 After review of the
Putman S, prosthesis implantation: a Dec;41(12):2503-2508. doi: document, this study looks
Pasquier G, prospective study 10.1007/s00264-017-3528-9. at metallic ion release in
Migaud H, Epub 2017 Jun 14. PMID: blood.
Drumez E, 28616704.
Girard J.
168 Li, Huiling; Yao, The progress on physicochemical SN Applied Sciences. 4/2020; After review of the
Zhigang; properties and biocompatibility of vol. 2. DOI: 10.1007/s42452- document, this is a review.
Zhang, Jian; tantalum-based metal bone 020-2480-2
Cai, Xinjia; Li, implants
Long; Liu, Gui;
Liu, Junjie; Cui,
Lin; Huang,
Junhui
169 Lee JH, Kwon Titanium-Silver Alloy Miniplates for J Oral Maxillofac Surg. 2016 After review of the
JS, Moon SK, Mandibular Fixation: In Vitro and Aug;74(8):1622.e1-1622.e12. document, this study looks
Uhm SH, Choi In Vivo Study doi: at a Ti-Ag.
BH, Joo UH, 10.1016/j.joms.2016.04.010.
Kim KM, Kim Epub 2016 Apr 23. PMID:
KN. 27192403.
170 Kręcisz B, Kieć- Allergy to orthopedic metal Int J Occup Med Environ After review of the
Świerczyńska implants - a prospective study Health. 2012 Sep;25(4):463-9. document, this study looks
M, doi: 10.2478/S13382-012- at the relationship
Chomiczewska- 0029-3. Epub 2012 Dec 3. between metal allergy and
Skóra D. PMID: 23212287. metal implant failure.
171 Kounis NG, Thrombus Formation Patterns in ASAIO J. 2014 Jul- After review of the
Soufras GD, HeartMate II Continuous-Flow Left Aug;60(4):369-71. doi: document, this is a review
Davlouros P, Ventricular Assist Devices: A 10.1097/MAT.00000000000 article.
Tsigkas G, Multifactorial Phenomenon 00081. PMID: 24727540.
Hahalis G. Involving Kounis Syndrome?
172 Kotsakis GA, Antimicrobial Agents Used in the J Periodontol. 2016 After review of the
Lan C, Barbosa Treatment of Peri-Implantitis Alter Jul;87(7):809-19. doi: document, this study looks
J, Lill K, Chen R, the Physicochemistry and 10.1902/jop.2016.150684. at chemotherapeutic
Rudney J, Cytocompatibility of Titanium Epub 2016 Feb 28. PMID: agents.
Aparicio C. Surfaces 26923474.
173 Kitagawa M, Current status of dental metal J Prosthodont Res. 2019 After review of the
Murakami S, allergy in Japan Jul;63(3):309-312. doi: document, this study looks
Akashi Y, Oka 10.1016/j.jpor.2019.01.003. at metal allergies.
H, Shintani T, Epub 2019 Feb 7. PMID:
Ogawa I, Inoue 30738702.
T, Kurihara H.

174 Kennon JC, Lee The effect of patient-reported J Shoulder Elbow Surg. 2020 After review of the
J, Songy C, metal allergies on the outcomes of Feb;29(2):296-301. doi: document, this study looks
Shukla D, shoulder arthroplasty 10.1016/j.jse.2019.06.006. at self-reported metal
Cofield RH, Epub 2019 Aug 16. PMID: allergies.
Sanchez-Sotelo 31427231.
J, Sperling JW.
175 Jurczyk, M.U.; Nanostructured titanium-45S5 Materials and Design. After review of the
Jurczyk, K.; Bioglass scaffold composites for 12/2011; vol. 32; 4882-4889. document, this study looks
Miklaszewski, medical applications DOI: at modified titanium.
A.; Jurczyk, M. 10.1016/j.matdes.2011.06.00
5
176 Jensen P, Cobalt allergy and suspected Contact Dermatitis. 2009 After review of the
Thyssen JP, aseptic lymphocyte-dominated Oct;61(4):238-9. doi: document, this is a case
Retpen JB, vascular-associated lesion following 10.1111/j.1600- report.
Menné T. total hip arthroplasty 0536.2009.01599.x. PMID:
19825098.
177 Hofmann SC, Titanium hypersensitivity causing Contact Dermatitis. 2018 After review of the
Plett M, Jansen painful intra-abdominal oedema Jul;79(1):48-49. doi: document, this is a case
S, Thomas P, after staple-fixed inguinal hernia 10.1111/cod.12985. Epub report.
Thölken KFM. repair 2018 Mar 9. PMID: 29521457.
178 Hensten- Casting alloys: side-effects Adv Dent Res. 1992 Sep;6:38- After review of the
Pettersen A. 43. doi: document, this is a review.
10.1177/0895937492006001
1401. PMID: 1292460.
179 Gustafson K, Metal release and metal allergy Acta Orthop. 2014 After review of the
Jakobsen SS, after total hip replacement with Aug;85(4):348-54. doi: document, this study looks
Lorenzen ND, resurfacing versus conventional 10.3109/17453674.2014.922 at metal on metal
Thyssen JP, hybrid prosthesis 730. Epub 2014 Jun 16. PMID: implants.
Johansen JD, 24930546; PMCID:
Bonefeld CM, PMC4105764.
Stilling M,
Baad-Hansen
T, Søballe K.
180 Gotman I. Characteristics of metals used in J Endourol. 1997 After review of the
implants Dec;11(6):383-9. doi: document, this is a review.
10.1089/end.1997.11.383.
PMID: 9440845.
181 Balčiūnas, E.; 3D printing hybrid organometallic Polymer International. After review of the
Baldock, S.; polymer-based biomaterials via 10/6/2019; vol. 68; 1928- document, this study looks
Dreižė, N.; laser two-photon polymerization 1940. DOI: 10.1002/pi.5909 at laser two-photon
Grubliauskaitė, polymerization.
M.; Coultas, S.;
Rochester, D.;
Valius, M.;
Hardy, J.;
Baltriukienė, D.

182 Alves F, Ribeiro Titanium allergy as a possible cause Contact Dermatitis. 2020 After review of the
JC, Alves M, of extrusion of a bone conduction Aug;83(2):148-149. doi: document, this is a case
Gonçalo M. ear implant 10.1111/cod.13566. Epub report.
2020 Jun 8. PMID: 32311757.


Titanium Literature Review

Uploaded by

Copyright:

Available Formats

Titanium Literature Review

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Titanium Literature Review

Uploaded by

Copyright:

Available Formats

Biocompatibility Literature

2. Biocompatibility Literature Review Summary .................................................................................................................. 3

3. Literature Search Protocol ..................................................................................................................................................... 7

4. Literature Search Results ........................................................................................................................................................ 9

5. Critical Evaluation of the Literature ..................................................................................................................................... 9

6. Biocompatibility Literature Review Conclusions ............................................................................................................ 15

Biocompatibility Literature Review 2/39

2. Biocompatibility Literature Review Summary

Numerous studies confirmed the repeated statement of biocompatibility of titanium.

Biocompatibility Literature Review 3/39

Biocompatibility Literature Review 4/39

Biocompatibility Literature Review 5/39

Biocompatibility Literature Review 6/39

3. Literature Search Protocol

Biocompatibility Literature Review 7/39

The searches were performed using the following search strings.

Biocompatibility Literature Review 8/39

4. Literature Search Results

5. Critical Evaluation of the Literature

Biocompatibility Literature Review 9/39

Biocompatibility Literature Review 10/39

8. Heakal & Shehata

Biocompatibility Literature Review 11/39

Biocompatibility Literature Review 12/39

Biocompatibility Literature Review 13/39

Biocompatibility Literature Review 14/39

6. Biocompatibility Literature Review Conclusions

Biocompatibility Literature Review 15/39

Table 1: List of Excluded Documents and Rationale for Exclusion

Biocompatibility Literature Review 16/39

Biocompatibility Literature Review 17/39

Biocompatibility Literature Review 18/39

Biocompatibility Literature Review 19/39

Biocompatibility Literature Review 20/39

Biocompatibility Literature Review 21/39

Biocompatibility Literature Review 22/39

Biocompatibility Literature Review 23/39

Biocompatibility Literature Review 24/39

Biocompatibility Literature Review 25/39

Biocompatibility Literature Review 26/39

Biocompatibility Literature Review 27/39

Biocompatibility Literature Review 28/39

Biocompatibility Literature Review 29/39

Biocompatibility Literature Review 30/39

Biocompatibility Literature Review 31/39

Biocompatibility Literature Review 32/39

Biocompatibility Literature Review 33/39

Biocompatibility Literature Review 34/39

Biocompatibility Literature Review 35/39

Biocompatibility Literature Review 36/39

Biocompatibility Literature Review 37/39

Biocompatibility Literature Review 38/39

Biocompatibility Literature Review 39/39

You might also like