Titanium Implant Housings and Surface Coatings

1. Titanium Implant Housings and Surface Coatings BME 525, Fall 2013, Duke University Matthew Pittman, Jin Zhu, Chia-Kuei Mo Begin

2. Main Menu Abstract Table of Contents Begin Tutorial Instructions Special Thanks Quiz Menu References

3. Tutorial Menu Basics/Background Fabrication Importance for Implantation Sterilization Processing Types of Implants

4. The tracking menu allows for cycling back to the main menu or through other subject menus. The information button links to the table of contents which allows access to any point of the tutorial. Instructions Click here to return to the main menu. Sometimes buttons become available at the top of the screen to denote more information within each topic. Click on buttons to view topics on left. Once a button is clicked, it turns red and becomes inactive. Choosing a different button deactivates the previous selection and activates the selection. When available, use the green button to view the next slide and the yellow button to view the previous slide. Previous Slide Next Slide

5. Abstract Main Menu The purpose of this tutorial is to understand why titanium is used as a housing material for implantable medical devices. The combination of physical and chemical properties allow for titanium to be an optimal material for device casings and protection. As result of its manufacturability, titanium can be formed and fabricated to form a complete housing for internal components which might be negatively affected by biological fluids within the body. It is because of this ability to form a hermetic seal and the biocompatibility of titanium that it is valuable in the medical industry in forming sealed housings for medical devices.

6. Special Thanks Next Slide • SuPingLyu, PhD • Senior Principal Scientist and Technical Fellow – Medtronic • PhD in Chemical Engineering from University of Minnesota • Dr. Lyu was vital in the understanding of design requirements needed for pacemakers. His input relating to both material selection and surface coatings provided a basis for the structure of this tutorial and provided the background rationale for the importance of titanium as a biomedical material.

7. Special Thanks Previous Slide • Stephen Robinson, MD • Assistant Professor of Medicine – Duke University • Duke Cardiology of Raleigh • Dr. Robinson provided critical knowledge into the aspects and difficulties associated with pacemaker surgery. His input of first-hand experiences proved valuable in understanding the failure analysis of the implantable devices and how medical professionals deal with such complications.

8. Background Overview Basics Physical Properties Chemical Properties [78]

9. Titanium Basics Basics Physical Properties Chemical Properties [78] Element: Ti Atomic Number: 22 Transition Metal Low Density: 4.506 g*cm-3 High Strength Silver Color

10. Titanium Physical Properties Basics Physical Properties Chemical Properties [50] • High strength to weight ratio • Ductile • High melting point: >1,650° C • Low electrical conductivity • Low thermal conductivity • Refractory metal • Resistance to heat and wear • Non-magnetic • Able to be used in MRI

11. Titanium Chemical Properties Basics Physical Properties Chemical Properties [53] • Titanium and titanium alloys oxidize when exposed to air • Forms titanium dioxide (TiO2) • Oxide layer is a thin film • Roughly 1-2 nanometers thick • Constantly growing • Can reach a thickness of 25 nanometers in four years • Thermodynamically very reactive metal • Negative redox potential: -1.63

12. Importance for Implantation Biocompatibility Biostability Hermiticity [50]

13. Titanium Biocompatibility Biocompatibility Angiogenesis Osseointegration Biostability Hermiticity “The ability of a material to perform with an appropriate host response in a specific application.” Non-toxic Most biocompatible metal Inert Supports osseointegration Resistant to biological environment [53]

14. Benefits of Titanium Osseointegration Angiogenesis Osseointegration Biocompatibility Biostability Hermiticity Next Slide Interactions/interface between living bone and implant material No soft tissue layer between bone and material • High dielectric constant • Allows for binding to bone and living tissue • TiO2: 100 • No adhesives required • Interface of titanium/tissue enhances angiogenesis • Controls osseointegration [51]

15. Osseointegration Angiogenesis Osseointegration Biocompatibility • Osseointegration occurs when bone cells attach themselves directly to the titanium surface, essentially locking the implant into the jaw bone. • This process was first discovered by a Swedish researcher, Per-Ingvar Brånemark, in the 1960's. • Placing dental implants into the jaw bones by controlled surgical procedures allow them to osseointegrate. Biostability Hermiticity [51] Previous Slide Next Slide

16. Osseointegration Angiogenesis Osseointegration Biocompatibility Bone Cell Biostability Implant Hermiticity Bone Titanium Surface [52] Scanning electron micrograph showing a bone cell attaching to titanium [52] Titanium implant (black) integrated into bone (red): Histologic section Previous Slide

17. Background Titanium Angiogenesis Angiogenesis Osseointegration Biocompatibility Biostability Hermiticity New blood vessels form from pre-existing vessels Increases osteoblast differentiation [57]

18. Titanium Biostability Biocompatibility Corrosion Resistance Biostability • Corrosion Resistant • Reliability of Material Hermiticity [54] When titanium oxidizes, it forms a protective film layer. “The ability of a material to maintain its physical and chemical integrity after implantation in living tissue.”

19. Titanium Alloys Corrosion Resistance Biocompatibility Corrosion Resistance Titanium Biostability Hermiticity • A stable, inert oxide film (TiO2) forms on the surface • Forms best when fresh titanium is exposed to oxygen • Oxide film can be self-healing in the presence of oxygen • Re-forms almost automatically if damaged • Alloy with palladium • Improves resistance to reducing acids • Sulphuric, hydrochloric, phosphoric • Raises critical temperature at which crevice erosion occurs • Ti-0.8%Ni-0.3%Mo • Ti-6%Al-7%Nb

20. Hermiticity Failure Analysis Material Selection Biocompatibility Most important property for in vivo use Biostability • Airtight • Electronics are separated from the outside environment • Function of bulk permeability and seal quality • Bulk metals are impermeable • Titanium Hermiticity [12]

21. Material Selection Failure Analysis Material Selection Biocompatibility • Metals are optimal materials • Lowest bulk permeability • Lower thickness = smaller components • Physical and chemical properties make titanium ideal for implantation Biostability Hermiticity [68] Next Slide

22. Material Selection Failure Analysis Material Selection Biocompatibility Biostability Hermiticity Previous Slide As with all implantable devices, the materials used must be nontoxic, inert, and sterilizable. Pacemakers are designed to be as small and nonintrusive as possible. Creating a ceramic housing that is less than 1 mm thick is not possible without a high risk of fracturing. The casing of a pacemaker also doubles as an electrode. A polymer housing would not be electrically conductive. Adding an electrode would complicated its design and add to its cost. Metal is very malleable and ductile. It allows for a variety of fabrication methods such was stamping and casting. Titanium is used for its high strength, thin form factor, and good design efficiency.

23. Failure Analysis Failure Analysis Material Selection Biocompatibility Biostability Hermiticity [70] Next Slide

24. Hermetic Seal Failure Failure Analysis Material Selection Biocompatibility Biostability Hermiticity [65] Previous Slide Next Slide Permeation leaks do not typically occur in laser welded joints. Instead, cracks or pore may cause direct leaks. If a grain boundary is large enough, it could traverse the entire thickness of the plane as seen in the first figure. Improper welding conditions may create pores by trapping flux in the seal shown in the figure below. [65]

25. Hermetic Seal Failure Failure Analysis Material Selection Biocompatibility Biostability Hermiticity Previous Slide In July 2005, Guidant release a recall several of its pacemaker models. They reported that, “hermetic sealing components susceptible to gradual degradation were mistakenly mixed with a much larger group of non-susceptible components.” Of the 78,000 devices manufactured, and estimated 0.17%-0.51% were affected. Reports confirmed stoppage of pacing output in some instances and sustained rapid pacing in others. Some of the malfunctions were fatal. This recall illustrates the importance of the pacemaker housing and consequences of its failure.

26. Quiz Menu Background Titanium Processing Titanium Fabrication Brain Quiz Deep Brain Stimulation (DBS) Arrhythmia Quiz

27. Question 1 Which of the following is not a physical property of titanium? High strength-to-weight ratio Low electrical conductivity Low melting point Low thermal conductivity

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30. Question 2 Osseointegration occurs when _______ and _______ bind together. • Bone and tissue • Tissue and implant • Bone and implant

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33. Question 3 Which of the following are correct regarding titanium oxide (TiO2)? It forms a thin film on the surface of titanium when exposed to oxygen. It has a high dialectric constant. It can regenerate itself if damaged when oxygen is present. All of the above

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36. Titanium Processing Processing/Methods Material Supply [50] [50]

37. Titanium Processing Processing/Methods Material Supply [55] Next Slide • 4 major steps • Reduction of titanium ore in sponge (porous) • Melting of sponge into ingot form (solid) • Primary fabrication – conversion of ingot into mill products • Billet, bar, sheet, strip, or tube • Secondary fabrication – formation into finished shapes • Made commercially through the Kroll process • Results in the higher cost of titanium • FFC Cambridge process is emerging as a replacement to the Kroll process

38. Kroll Process FFC Cambridge Process Titanium Processing Processing/Methods Material Supply Previous Slide Next Slide • Complex and expensive batch process • The oxide is converted to chloride through carbochlorination • Pass chlorine gas over hit titanium to form TiCl4 • Utilize fractional distillation to condense and purify final product • Reduced with magnesium and argon • Utilizes titanium dioxide powder to make a powder or sponge • Cheaper and easier to make titanium alloys • Cathodic reduction of the metal into molten salts • Anode attracts oxygen from the oxide

39. FFC Cambridge Process Processing/Methods Material Supply [55] The FFC Cambridge Process may eventually replace the Kroll process which would lead to cheaper processing costs for titanium. As a result, titanium would become less rare and cheaper. Previous Slide Next Slide

40. Titanium Processing Processing/Methods Material Supply Previous Slide • Titanium is non-ferromagnetic • Suitable for use in Magnetic Resonance Imaging (MRI) • In preparation for implantation, a high-temperature plasma arc is used to remove the surface atoms • This allows for fresh titanium to become exposing • Exposed titanium is instantly oxidized

41. Material Supply Processing/Methods Material Supply [50] “More than 1,000 tones of titanium devices of every description and function are implanted in patients worldwide every year.” Titanium is the seventh most abundant metal on Earth. In 2011, 186,000 tons of titanium metal sponge were produced.

42. Question 1 Titanium is processed in the following order: Primary fabrication, reduction into sponge, secondary fabrication, melting into ingot Reduction into sponge, melting into ingot, primary fabrication, secondary fabrication Melting into ingot, reduction into sponge, primary fabrication, secondary fabrication Secondary fabrication, primary fabrication, melting into ingot, reduction into sponge

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45. Question 2 Which of the following is a sterilization method for titanium? • Cold Chemical • Ethylene Oxide Gas • Steam • None of the Above

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48. Question 3 Which of the following is true of the manufacturability of titanium? It is solderable by itself. It has no requirements for welding. It can be made into sheet form. None of the above

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