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Titanium biocompatibility

Titanium was first introduced into surgeries in the 1950s after having been used in dentistry for a decade prior.[1] It is now the metal of choice for prosthetics, internal fixation, inner body devices, and instrumentation. Titanium is used from head to toe in biomedical implants. One can find titanium in neurosurgery, bone conduction hearing aids, false eye implants, spinal fusion cages, pacemakers, toe implants, and shoulder/elbow/hip/knee replacements along with many more. The main reason why titanium is often used in the body is due to titanium's biocompatibility and, with surface modifications, bioactive surface. The surface characteristics that affect biocompatibility are surface texture, steric hindrance, binding sites, and hydrophobicity (wetting). These characteristics are optimized to create an ideal cellular response. Some medical implants, as well as parts of surgical instruments are coated with titanium nitride (TiN).

Titanium dental implants

Biocompatibility edit

Titanium is considered the most biocompatible metal due to its resistance to corrosion from bodily fluids, bio-inertness, capacity for osseointegration, and high fatigue limit. Titanium's ability to withstand the harsh bodily environment is a result of the protective oxide film that forms naturally in the presence of oxygen. The oxide film is strongly adhered, insoluble, and chemically impermeable, preventing reactions between the metal and the surrounding environment.[citation needed]

Osseointegration interaction and proliferation edit

High energy surfaces induce angiogenesis during osseointegration edit

It has been suggested that titanium's capacity for osseointegration stems from the high dielectric constant of its surface oxide, which does not denature proteins (like tantalum, and cobalt alloys).[2] Its ability to physically bond with bone gives titanium an advantage over other materials that require the use of an adhesive to remain attached. Titanium implants last longer and much higher forces are required to break the bonds that join them to the body compared to their alternatives.[3]

Surface properties determine osseointegration edit

The surface properties of a biomaterial play an important role in determining cellular response (cell adhesion and proliferation) to the material. Titanium's microstructure and high surface energy enable it to induce angiogenesis, which assists in the process of osseointegration.[4]

Surface energy edit

Redox potential edit

Titanium can have many different standard electrode potentials depending on its oxidation state. Solid titanium has a standard electrode potential of -1.63V. Materials with a greater standard electrode potential are more easily reduced, making them better oxidizing agents.[5] As can be seen in the table below, solid titanium prefers to undergo oxidation, making it a better reducing agent.

Half reaction Standard electrode potential (V)
Ti2+ + 2 e → Ti(s) -1.63[5]
Ti3+ + 3 e → Ti(s) -1.21[6]
TiO2+ + 2 H+ + 4 e → Ti(s) +  H2O -0.86[7]
2 TiO2(s) + 2 H+ + 2 e → Ti2O3(s) +  H2O -0.56[7]
Ti2+(aq)/M3+(aq) -0.36[6]

Surface coating edit

 
Cellular binding to a titanium oxide surface

Titanium naturally passivates, forming an oxide film that becomes heterogeneous and polarized as a function of exposure time to bodily environments.[8] This leads to the increased adsorption of hydroxyl groups, lipoproteins, and glycolipids over time.[8] The adsorption of these compounds changes how the material interacts with the body and can improve biocompatibility. In titanium alloys such as Ti-Zr and Ti-Nb, zirconium and niobium ions that are liberated due to corrosion are not released into the patient's body, but rather added to the passivation layer.[9] The alloying elements in the passive layer add a degree of biocompatibility and corrosion resistance depending on the original alloy composition of the bulk metal prior to corrosion.

Protein surface concentration, ( ), is defined by the equation

 [10]

where QADS is the surface charge density in C⋅cm−2, M is the molar mass of the protein in g⋅mol−1, n is the number of electrons transferred (in this case, one electron for each protonated amino group in the protein), and F is the Faraday constant in C⋅mol−1.

The equation for collision frequency is as follows:

 [10]

where D = 8.83 × 10−7 cm2⋅s−1 is the diffusion coefficient of the BSA molecule at 310 K, d = 7.2 nm is the "diameter" of the proteinwhich is equivalent to twice the Stokes radius, NA = 6.023 × 1023 mol−1 is the Avogadro constant, and c* = 0.23 g⋅L−1 (3.3 μM) is the critical bulk supersaturation concentration.

Wetting and solid surface edit

 
The droplet on the left has a contact angle between 90 and 180 degrees, rendering the interaction between the solid and the liquid relatively weak. In contrast, the droplet on the right has a contact angle between 0 and 90 degrees making the interaction between the solid and the liquid strong.

Wetting occurs as a function of two parameters: surface roughness and surface fraction.[11] By increasing wetting, implants can decrease the time required for osseointegration by allowing cells to more readily bind to the surface of an implant.[3] Wetting of titanium can be modified by optimizing process parameters such as temperature, time, and pressure (shown in table below). Titanium with stable oxide layers predominantly consisting of TiO2 result in improved wetting of the implant in contact with physiological fluid.[12]

Surface Wetting angle (degrees) Pressure (mbar) during processing Temperature (degrees C) during processing Other surface processing
Bare Ti ~50[10] - - None
TiO2 TiO Ti4O7 TiO4 (Planar) ~33[12] 2.2 700 Oxidation
TiO2 TiO Ti4O7 (Planar) ~45[12] 4 700 Oxidation
TiO2 TiO Ti4O7 TiO4 (Hollow) ~32[12] 2.2 400 Oxidation
TiO2 TiO Ti4O7 (Hollow) ~25[12] 2.6 500 Oxidation
TiO2 TiO Ti4O7 (Hollow) ~8[12] 4 400 Oxidation
TiO2 TiO Ti4O7 (Hollow) ~20[12] 4 500 Oxidation
Ti with roughened surface 79.5 ± 4.6[13] - - Machined surface
Ti with alkali-treated surface 27.2 ± 6.9[13] - - Bio-surface

Adsorption edit

Corrosion edit

Mechanical abrasion of the titanium oxide film leads to an increased rate of corrosion.[14]

Titanium and its alloys are not immune to corrosion when in the human body. Titanium alloys are susceptible to hydrogen absorption which can induce precipitation of hydrides and cause embrittlement, leading to material failure.[14] "Hydrogen embrittlement was observed as an in vivo mechanism of degradation under fretting-crevice corrosion conditions resulting in TiH formation, surface reaction and cracking inside Ti/Ti modular body tapers."[14] Studying and testing titanium behavior in the body allow us to avoid malpractices that would cause a fatal breakdown in the implant, like the usage of dental products with high fluoride concentration or substances capable of lowering the pH of the media around the implant.[15]

Adhesion edit

 
A metal surface with grafted polymers multimeric constructs to promote cell binding. The polymers grafted on the metal surface are brushed, increasing the contact area for cell integration

The cells at the implant interface are highly sensitive to foreign objects. When implants are installed into the body, the cells initiate an inflammatory response which could lead to encapsulation, impairing the functioning of the implanted device.[16]

The ideal cell response to a bioactive surface is characterized by biomaterial stabilization and integration, as well as the reduction of potential bacterial infection sites on the surface. One example of biomaterial integration is a titanium implant with an engineered biointerface covered with biomimetic motifs. Surfaces with these biomimetic motifs have shown to enhance integrin binding and signaling and stem cell differentiation. Increasing the density of ligand clustering also increased integrin binding. A coating consisting of trimers and pentamers increased the bone-implant contact area by 75% when compared to the current clinical standard of uncoated titanium.[17] This increase in area allows for increased cellular integration, and reduces rejection of implanted device. The Langmuir isotherm:

 ,[10]

where c is the concentration of the adsorbate   is the max amount of adsorbed protein, BADS is the affinity of the adsorbate molecules toward adsorption sites. The Langmuir isotherm can be linearized by rearranging the equation to,

 [10]

This simulation is a good approximation of adsorption to a surface when compared to experimental values.[10] The Langmuir isotherm for adsorption of elements onto the titanium surface can be determined by plotting the know parameters. An experiment of fibrinogen adsorption on a titanium surface "confirmed the applicability of the Langmuir isotherm in the description of adsorption of fibrinogen onto Ti surface."[10]

See also edit

References edit

  1. ^ Fischer J (December 2000). "Mechanical, thermal, and chemical analyses of the binary system Au-Ti in the development of a dental alloy". J. Biomed. Mater. Res. 52 (4): 678–86. doi:10.1002/1097-4636(20001215)52:4<678::AID-JBM12>3.0.CO;2-P. PMID 11033550.
  2. ^ Black, Jonathan (January 1994). "Biologic performance of tantalum". Clinical Materials. 16 (3): 167–173. doi:10.1016/0267-6605(94)90113-9.
  3. ^ a b Raines, Andrew L.; Olivares-Navarrete, Rene; Wieland, Marco; Cochran, David L.; Schwartz, Zvi; Boyan, Barbara D. (2010). "Regulation of angiogenesis during osseointegration by titanium surface microstructure and energy". Biomaterials. 31 (18): 4909–17. doi:10.1016/j.biomaterials.2010.02.071. PMC 2896824. PMID 20356623.
  4. ^ http://titaniumthemetal.org/Resources/DataSheetMedical.pdf [bare URL PDF]
  5. ^ a b . Archived from the original on 2013-06-18. Retrieved 2012-10-23.
  6. ^ a b Brown, Doc. "Chemistry of Titanium".
  7. ^ a b Winter, Mark. "Titanium compounds".
  8. ^ a b Healy, Kevin E.; Ducheyne, Paul (1991). "A physical model for the titanium-tissue interface". ASAIO Transactions. 37 (3): M150–1. PMID 1751087.
  9. ^ Long, Marc; Rack, H.J (1998). "Titanium alloys in total joint replacement—a materials science perspective". Biomaterials. 19 (18): 1621–39. doi:10.1016/S0142-9612(97)00146-4. PMID 9839998.
  10. ^ a b c d e f g Jackson, Douglas R.; Omanović, Saša; Roscoe, Sharon G. (2000). "Electrochemical Studies of the Adsorption Behavior of Serum Proteins on Titanium". Langmuir. 16 (12): 5449–57. doi:10.1021/la991497x.
  11. ^ Bico, José; Thiele, Uwe; Quéré, David (2002). "Wetting of textured surfaces". Colloids and Surfaces A: Physicochemical and Engineering Aspects. 206 (1–3): 41–6. doi:10.1016/S0927-7757(02)00061-4.
  12. ^ a b c d e f g Silva, M.A.M.; Martinelli, A.E.; Alves, C.; Nascimento, R.M.; Távora, M.P.; Vilar, C.D. (2006). "Surface modification of Ti implants by plasma oxidation in hollow cathode discharge". Surface and Coatings Technology. 200 (8): 2618–26. doi:10.1016/j.surfcoat.2004.12.027.
  13. ^ a b Strnad, Jakub; Strnad, Zdeněk; Šesták, Jaroslav; Urban, Karel; Povýšil, Ctibor (2007). "Bio-activated titanium surface utilizable for mimetic bone implantation in dentistry—Part III: Surface characteristics and bone–implant contact formation". Journal of Physics and Chemistry of Solids. 68 (5–6): 841–5. Bibcode:2007JPCS...68..841S. doi:10.1016/j.jpcs.2007.02.040.
  14. ^ a b c Rodrigues, Danieli C.; Urban, Robert M.; Jacobs, Joshua J.; Gilbert, Jeremy L. (2009). "In vivo severe corrosion and hydrogen embrittlement of retrieved modular body titanium alloy hip-implants". Journal of Biomedical Materials Research Part B: Applied Biomaterials. 88 (1): 206–19. doi:10.1002/jbm.b.31171. PMC 2667129. PMID 18683224.
  15. ^ (PDF). Archived from the original (PDF) on 2016-03-04. Retrieved 2015-06-01.{{cite web}}: CS1 maint: archived copy as title (link)
  16. ^ Franz, Sandra; Rammelt, Stefan; Scharnweber, Dieter; Simon, Jan C. (2011). "Immune responses to implants – A review of the implications for the design of immunomodulatory biomaterials". Biomaterials. 32 (28): 6692–709. doi:10.1016/j.biomaterials.2011.05.078. PMID 21715002.
  17. ^ Petrie, T. A.; Raynor, J. E.; Dumbauld, D. W.; Lee, T. T.; Jagtap, S.; Templeman, K. L.; Collard, D. M.; Garcia, A. J. (2010). "Multivalent Integrin-Specific Ligands Enhance Tissue Healing and Biomaterial Integration". Science Translational Medicine. 2 (45): 45ra60. doi:10.1126/scitranslmed.3001002. PMC 3128787. PMID 20720217.

titanium, biocompatibility, titanium, first, introduced, into, surgeries, 1950s, after, having, been, used, dentistry, decade, prior, metal, choice, prosthetics, internal, fixation, inner, body, devices, instrumentation, titanium, used, from, head, biomedical,. Titanium was first introduced into surgeries in the 1950s after having been used in dentistry for a decade prior 1 It is now the metal of choice for prosthetics internal fixation inner body devices and instrumentation Titanium is used from head to toe in biomedical implants One can find titanium in neurosurgery bone conduction hearing aids false eye implants spinal fusion cages pacemakers toe implants and shoulder elbow hip knee replacements along with many more The main reason why titanium is often used in the body is due to titanium s biocompatibility and with surface modifications bioactive surface The surface characteristics that affect biocompatibility are surface texture steric hindrance binding sites and hydrophobicity wetting These characteristics are optimized to create an ideal cellular response Some medical implants as well as parts of surgical instruments are coated with titanium nitride TiN Titanium dental implants Contents 1 Biocompatibility 1 1 Osseointegration interaction and proliferation 1 1 1 High energy surfaces induce angiogenesis during osseointegration 1 1 2 Surface properties determine osseointegration 2 Surface energy 2 1 Redox potential 2 2 Surface coating 2 3 Wetting and solid surface 3 Adsorption 3 1 Corrosion 3 2 Adhesion 4 See also 5 ReferencesBiocompatibility editTitanium is considered the most biocompatible metal due to its resistance to corrosion from bodily fluids bio inertness capacity for osseointegration and high fatigue limit Titanium s ability to withstand the harsh bodily environment is a result of the protective oxide film that forms naturally in the presence of oxygen The oxide film is strongly adhered insoluble and chemically impermeable preventing reactions between the metal and the surrounding environment citation needed Osseointegration interaction and proliferation edit High energy surfaces induce angiogenesis during osseointegration edit It has been suggested that titanium s capacity for osseointegration stems from the high dielectric constant of its surface oxide which does not denature proteins like tantalum and cobalt alloys 2 Its ability to physically bond with bone gives titanium an advantage over other materials that require the use of an adhesive to remain attached Titanium implants last longer and much higher forces are required to break the bonds that join them to the body compared to their alternatives 3 Surface properties determine osseointegration edit The surface properties of a biomaterial play an important role in determining cellular response cell adhesion and proliferation to the material Titanium s microstructure and high surface energy enable it to induce angiogenesis which assists in the process of osseointegration 4 Surface energy editRedox potential edit Titanium can have many different standard electrode potentials depending on its oxidation state Solid titanium has a standard electrode potential of 1 63V Materials with a greater standard electrode potential are more easily reduced making them better oxidizing agents 5 As can be seen in the table below solid titanium prefers to undergo oxidation making it a better reducing agent Half reaction Standard electrode potential V Ti2 2 e Ti s 1 63 5 Ti3 3 e Ti s 1 21 6 TiO2 2 H 4 e Ti s H2O 0 86 7 2 TiO2 s 2 H 2 e Ti2O3 s H2O 0 56 7 Ti2 aq M3 aq 0 36 6 Surface coating edit nbsp Cellular binding to a titanium oxide surface Titanium naturally passivates forming an oxide film that becomes heterogeneous and polarized as a function of exposure time to bodily environments 8 This leads to the increased adsorption of hydroxyl groups lipoproteins and glycolipids over time 8 The adsorption of these compounds changes how the material interacts with the body and can improve biocompatibility In titanium alloys such as Ti Zr and Ti Nb zirconium and niobium ions that are liberated due to corrosion are not released into the patient s body but rather added to the passivation layer 9 The alloying elements in the passive layer add a degree of biocompatibility and corrosion resistance depending on the original alloy composition of the bulk metal prior to corrosion Protein surface concentration G displaystyle Gamma nbsp is defined by the equationG Q ADS M n F displaystyle Gamma Q text ADS M over nF nbsp 10 where QADS is the surface charge density in C cm 2 M is the molar mass of the protein in g mol 1 n is the number of electrons transferred in this case one electron for each protonated amino group in the protein and F is the Faraday constant in C mol 1 The equation for collision frequency is as follows v c 2 p D c d N A displaystyle v text c 2 pi DcdN text A nbsp 10 where D 8 83 10 7 cm2 s 1 is the diffusion coefficient of the BSA molecule at 310 K d 7 2 nm is the diameter of the proteinwhich is equivalent to twice the Stokes radius NA 6 023 1023 mol 1 is the Avogadro constant and c 0 23 g L 1 3 3 mM is the critical bulk supersaturation concentration Wetting and solid surface edit nbsp The droplet on the left has a contact angle between 90 and 180 degrees rendering the interaction between the solid and the liquid relatively weak In contrast the droplet on the right has a contact angle between 0 and 90 degrees making the interaction between the solid and the liquid strong Wetting occurs as a function of two parameters surface roughness and surface fraction 11 By increasing wetting implants can decrease the time required for osseointegration by allowing cells to more readily bind to the surface of an implant 3 Wetting of titanium can be modified by optimizing process parameters such as temperature time and pressure shown in table below Titanium with stable oxide layers predominantly consisting of TiO2 result in improved wetting of the implant in contact with physiological fluid 12 Surface Wetting angle degrees Pressure mbar during processing Temperature degrees C during processing Other surface processing Bare Ti 50 10 None TiO2 TiO Ti4O7 TiO4 Planar 33 12 2 2 700 Oxidation TiO2 TiO Ti4O7 Planar 45 12 4 700 Oxidation TiO2 TiO Ti4O7 TiO4 Hollow 32 12 2 2 400 Oxidation TiO2 TiO Ti4O7 Hollow 25 12 2 6 500 Oxidation TiO2 TiO Ti4O7 Hollow 8 12 4 400 Oxidation TiO2 TiO Ti4O7 Hollow 20 12 4 500 Oxidation Ti with roughened surface 79 5 4 6 13 Machined surface Ti with alkali treated surface 27 2 6 9 13 Bio surfaceAdsorption editCorrosion edit Mechanical abrasion of the titanium oxide film leads to an increased rate of corrosion 14 Titanium and its alloys are not immune to corrosion when in the human body Titanium alloys are susceptible to hydrogen absorption which can induce precipitation of hydrides and cause embrittlement leading to material failure 14 Hydrogen embrittlement was observed as an in vivo mechanism of degradation under fretting crevice corrosion conditions resulting in TiH formation surface reaction and cracking inside Ti Ti modular body tapers 14 Studying and testing titanium behavior in the body allow us to avoid malpractices that would cause a fatal breakdown in the implant like the usage of dental products with high fluoride concentration or substances capable of lowering the pH of the media around the implant 15 Adhesion edit nbsp A metal surface with grafted polymers multimeric constructs to promote cell binding The polymers grafted on the metal surface are brushed increasing the contact area for cell integration The cells at the implant interface are highly sensitive to foreign objects When implants are installed into the body the cells initiate an inflammatory response which could lead to encapsulation impairing the functioning of the implanted device 16 The ideal cell response to a bioactive surface is characterized by biomaterial stabilization and integration as well as the reduction of potential bacterial infection sites on the surface One example of biomaterial integration is a titanium implant with an engineered biointerface covered with biomimetic motifs Surfaces with these biomimetic motifs have shown to enhance integrin binding and signaling and stem cell differentiation Increasing the density of ligand clustering also increased integrin binding A coating consisting of trimers and pentamers increased the bone implant contact area by 75 when compared to the current clinical standard of uncoated titanium 17 This increase in area allows for increased cellular integration and reduces rejection of implanted device The Langmuir isotherm G B ADS G max 1 c B ADS displaystyle Gamma B text ADS Gamma text max over 1 cB text ADS nbsp 10 where c is the concentration of the adsorbate G displaystyle Gamma nbsp is the max amount of adsorbed protein BADS is the affinity of the adsorbate molecules toward adsorption sites The Langmuir isotherm can be linearized by rearranging the equation to c G 1 B ADS G max c G max displaystyle c over Gamma 1 over B text ADS Gamma text max c over Gamma text max nbsp 10 This simulation is a good approximation of adsorption to a surface when compared to experimental values 10 The Langmuir isotherm for adsorption of elements onto the titanium surface can be determined by plotting the know parameters An experiment of fibrinogen adsorption on a titanium surface confirmed the applicability of the Langmuir isotherm in the description of adsorption of fibrinogen onto Ti surface 10 See also editBiomaterials mechanical properties Metals in medicine Titanium adhesive bondingReferences edit Fischer J December 2000 Mechanical thermal and chemical analyses of the binary system Au Ti in the development of a dental alloy J Biomed Mater Res 52 4 678 86 doi 10 1002 1097 4636 20001215 52 4 lt 678 AID JBM12 gt 3 0 CO 2 P PMID 11033550 Black Jonathan January 1994 Biologic performance of tantalum Clinical Materials 16 3 167 173 doi 10 1016 0267 6605 94 90113 9 a b Raines Andrew L Olivares Navarrete Rene Wieland Marco Cochran David L Schwartz Zvi Boyan Barbara D 2010 Regulation of angiogenesis during osseointegration by titanium surface microstructure and energy Biomaterials 31 18 4909 17 doi 10 1016 j biomaterials 2010 02 071 PMC 2896824 PMID 20356623 http titaniumthemetal org Resources DataSheetMedical pdf bare URL PDF a b Standard Reduction Potentials 25oC Archived from the original on 2013 06 18 Retrieved 2012 10 23 a b Brown Doc Chemistry of Titanium a b Winter Mark Titanium compounds a b Healy Kevin E Ducheyne Paul 1991 A physical model for the titanium tissue interface ASAIO Transactions 37 3 M150 1 PMID 1751087 Long Marc Rack H J 1998 Titanium alloys in total joint replacement a materials science perspective Biomaterials 19 18 1621 39 doi 10 1016 S0142 9612 97 00146 4 PMID 9839998 a b c d e f g Jackson Douglas R Omanovic Sasa Roscoe Sharon G 2000 Electrochemical Studies of the Adsorption Behavior of Serum Proteins on Titanium Langmuir 16 12 5449 57 doi 10 1021 la991497x Bico Jose Thiele Uwe Quere David 2002 Wetting of textured surfaces Colloids and Surfaces A Physicochemical and Engineering Aspects 206 1 3 41 6 doi 10 1016 S0927 7757 02 00061 4 a b c d e f g Silva M A M Martinelli A E Alves C Nascimento R M Tavora M P Vilar C D 2006 Surface modification of Ti implants by plasma oxidation in hollow cathode discharge Surface and Coatings Technology 200 8 2618 26 doi 10 1016 j surfcoat 2004 12 027 a b Strnad Jakub Strnad Zdenek Sestak Jaroslav Urban Karel Povysil Ctibor 2007 Bio activated titanium surface utilizable for mimetic bone implantation in dentistry Part III Surface characteristics and bone implant contact formation Journal of Physics and Chemistry of Solids 68 5 6 841 5 Bibcode 2007JPCS 68 841S doi 10 1016 j jpcs 2007 02 040 a b c Rodrigues Danieli C Urban Robert M Jacobs Joshua J Gilbert Jeremy L 2009 In vivo severe corrosion and hydrogen embrittlement of retrieved modular body titanium alloy hip implants Journal of Biomedical Materials Research Part B Applied Biomaterials 88 1 206 19 doi 10 1002 jbm b 31171 PMC 2667129 PMID 18683224 Archived copy PDF Archived from the original PDF on 2016 03 04 Retrieved 2015 06 01 a href Template Cite web html title Template Cite web cite web a CS1 maint archived copy as title link Franz Sandra Rammelt Stefan Scharnweber Dieter Simon Jan C 2011 Immune responses to implants A review of the implications for the design of immunomodulatory biomaterials Biomaterials 32 28 6692 709 doi 10 1016 j biomaterials 2011 05 078 PMID 21715002 Petrie T A Raynor J E Dumbauld D W Lee T T Jagtap S Templeman K L Collard D M Garcia A J 2010 Multivalent Integrin Specific Ligands Enhance Tissue Healing and Biomaterial Integration Science Translational Medicine 2 45 45ra60 doi 10 1126 scitranslmed 3001002 PMC 3128787 PMID 20720217 Retrieved from https en wikipedia org w index php title Titanium biocompatibility amp oldid 1220385051, wikipedia, wiki, book, books, library,

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