Scientific Article 3 : Introduction to Metals for Medical Devices

Posted on 17 November 2013 (1,922 views)
by Hendra Hermawan

by Hendra Hermawan

Hendra Hermawan is a member of IMM. He received his PhD in Materials Engineering from Laval University, Canada in 2009. He did a postdoc with a Barcelona-based medical devices manufacturer for two years before joining the Faculty of Biosciences and Medical Engineering, Universiti Teknologi Malaysia. His research interests include metals for biomedical applications and corrosion engineering. He is a registered CEng with the Engineering Council UK and a member of IOM3. He holds a CP-2 certificate from NACE International. He serves as Adjunct Professor at the Department of Mining, Metallurgical and Materials Engineering, Laval University. He also serves as an Editorial Board Member of Journal of Orthopaedic Translation (Elsevier). To contact the author, please visit his website: http://fbme.utm.my/hendra

 

1. Introduction
In January 2012, the Parliament of Malaysia has passed the Law of Malaysia Act 737 known as the Malaysian Medical Device Act (MDA) 2012. The MDA 2012 regulates the registration of medical device and conformity assessment body, license and permit, and enforcement. One of the most important aspects of medical devices is biomaterials, the materials of which the devices are made. In Malaysia, research on biomaterials has been growing rapidly. For the last 3 years there are more than thousand of publications as recorded in Scopus, the most referred scientific database, with the leading institutions including Universiti Teknologi Malaysia (UTM), Universiti Malaya (UM), Universiti Kebangsaan Malaysia (UKM), Universiti Sains Malaysia (USM), International Islamic University of Malaysia (IIUM) and Advanced Materials Research (AMREC) SIRIM.

In line with the MDA 2012 enactment, this article aims to introduce metals, as the most used biomaterials for medical devices. Metals for medical devices have experienced vast devel-opment and clinical uses since the invention of stainless steel in 1920s. It was then fostered by the formation of ASTM Committee F04 on Medical and Surgical Materials and Devices in 1962 that played an important role for the practice and standardization. A great variety of corrosion resistant metals have been developed and used for medical devices (especially implants) including the class of 316L stainless steels, cobalt-chromium (Co-Cr) alloys and ti-tanium (Ti) and its alloys. New generation of alloys has been made nickel (Ni) free via novel processing including nano-processing and amorphization. Other development exploited the concept of biodegradable rather than inert metals where temporary medical implants, that function only during specific period and then degrade, were targeted. This article is mostly  taken from the author’s book entitled “Biodegradable Metals: From Concept to Applications” with permission from the publisher, Springer.

 

2. Metal Implants
Metals were chosen for use in the intervention of trauma, disease or malfunction of organs where loading present. In the early development, insufficient strength and corrosion were two main problems faced by metal implants [1]. The introduction of corrosion resistant 18-8 stainless steel solved most of corrosion problem and thereafter stimulated the vast develop-ment and clinical use of metal implants. Nowadays, hundreds of type of metals for implants has been used. In general they can be grouped into: 1) stainless steel alloys; 2) Co-Cr alloys; 3) Ti and its alloys; and 4) precious alloys. Figure 1 shows some examples of medical implants where metals are used. Metals are used by considering their two key features: the structural function and the inert-ness. However in the current development, it is desirable that an implant also possesses bi-oactivities or biofunctionalities such as blood compatibility and bone conductivity. Therefore surface modifications are employed. For example, metals have been coated with hydroxy-apatite to provide bone conductivity [2], or with biopolymers to improve blood compatibility [3]. Development on metallic biomaterials includes those composed of nontoxic and allergy-free elements [4] and biodegradable metals targeted for use as temporary implants [5].

fig1

Fig. 1 Examples of metal implants: (a) hip and elbow implants, (b) knee arthroplasty, (c) craniofacial plates. Courtesy of MediTeg, Universiti Teknologi Malaysia

 

3. Requirements for Metal Implants
In clinical practice, metal implants are subjected to the conditions as described in Table 1. First of all, they are used in contact with living tissues thus they need to be biocompatible. Other functional characteristics that are important include adequate mechanical properties such as strength, stiffness, and fatigue properties; and also appropriate density.

tbl1

Table 1 Body environments to which metal implants are subjected

Metal implants are also required to be non-magnetic and have high density in order to be compatible with magnetic resonance imaging (MRI) techniques and to be visible under X-ray imaging, respectively. Most of artificial implants are subjected to loads, either static or repeti-tive, and this condition requires an excellent combination of strength and ductility. This is the superiority of metals over other materials such as polymers and ceramics.

In addition, specific requirements of metals depend on the specific implant applications. Stents and stent grafts are implanted to open stenotic (narrowed) blood vessels; therefore, they require plasticity for expansion and rigidity for maintaining dilatation. In orthopaedic implant applications, metals are required to have excellent toughness, elasticity, rigidity, strength and resistance to fracture. Additionally, for total joint replacement metals are needed to be wear resistance to avoid debris formation from friction. Dental restoration requires strong and rigid metals and even the shape memory effect for better clinical outcomes.

 

4. Metallic BiomaterialsThe selection of metal used in biomedical depends on the specific implant applications. The 316L type stainless steel (SS316L) is still the most widely used alloys in all implant division ranging from orthopaedic to dentistry. However, when an implant requires high wear re-sistance such as an artificial joint, Co-Cr alloy would better serve. Table 2 summarized type of metals generally used for different implants division.

 tbl2

Table 2 Implants division and type of metals used

Chemical composition is one of the basic characteristics of metals which determine the formed microstructure and phases, thus their properties, i.e. mechanical properties. For ex-ample, the addition of Aluminum (Al) and Vanadium (V) into pure Ti greatly increase its ten-sile strength. Beside composition, metallurgical state of the metals changes their mechanical properties, i.e. annealed condition has better ductility than that of cold worked. The process to synthesis metals also affects their microstructure and properties. As an example, cast metal implants usually possess lower strength than those made by forging.

4.1. Stainless steels
Till now, the three most used metals for implants are stainless steel, Co-Cr alloys and Ti al-loys. The first stainless steel used for implants contained ~18wt% Chromium (Cr) and ~8wt% Ni made it more resistant to corrosion and stronger than steel. The addition of Molybdenum (Mo) further improves its corrosion resistance, known as type 316 stainless steel. Further advancement was the reduction of its Carbon (C) content from 0.08 to 0.03wt% that improves corrosion resistance to Chloride (Cl)-containing solution, and named as 316L. The ASTM has standardized stainless steel for surgical implants in their F138 [10], F899 [11] and F2181 [12] standards.

4.2. Co-Cr alloys
These alloys are generally known for their excellent wear resistance where they have been in use in dentistry for many decades and in making artificial joints. Wrought Co- Ni-Cr-Mo alloy, for example, has been used for making loaded joints such as the hip and knee arthroplasty. ASTM standards covered these alloys include F75 [13], F90 [14], F562 [15], F1537 [16]. 

4.3. Ti and Ti alloys 
Having density only 4.5 g/cm3, Ti is featured by its light weight compared to 7.9 g/cm3 for 316 stainless steel and 8.3 g/cm3 for cast Co-Cr-Mo alloys [17]. The most known Ti alloys, Ti-6Al-4V, are considered as having excellent tensilestrength and pitting corrosion resistance. When alloyed with Ni, Ti-Ni alloy or better known as Nitinol, possesses a shape memory effect which is an attractive property used for example in dental restoration wiring. Titanium and its alloys for medical applications were covered in ASTMstandards F67 [18], F136 [19] and F2063 [20].

4.4. Precious alloys
Precious metals and alloys such as Gold (Au), Silver (Ag), Platinum (Pt) and their alloys are mostly known in dentistry due to their good castability, ductility and resistance to corrosion. Included into dental alloys are Au-Ag-Copper (Cu) system, Au-Ag-Cu with the addition of Zinc (Zn) and Tin (Sn) known as dental solder, and Au-Pt-Palladium (Pd) system used for porcelain-fused-to-metal for teeth repairs [21].

4.5. Other metal and alloys
Tantalum (Ta), amorphous alloys and biodegradable metals are among other metals used for implants. Due to its excellent X-ray visibility and low magnetic susceptibility, Ta is often used for X-ray markers for stents. Interesting properties have been shown by amorphous alloys compared to its crystalline counterparts whereas they exhibit a higher corrosion resistance, wear resistance, tensile strength and fatigue strength. Amorphous alloys like that of Zirconium (Zr)-based [22] with its low Young’s modulus may miniaturized metal implants. Amorphous Magnesium (Mg)-based alloys have also shown a favorable degradation behav-ior where hydrogen evolution was not observed [23].

 

5. Non-metallic Biomaterials
Biomaterial is defined as a nonviable material used in a medical device which is intended to interact with biological systems [24]. Biomaterials are used to make devices to replace a part or a function of the body in a reliable, safe, physiologically acceptable and economic manner [25]. It covers a broad range of materials from metals, ceramics and polymers, to compo-sites. Table 3 summarizes materials commonly used as biomaterials.

tbl3
Table 3 Materials commonly used for biomedical applications

5.1. Ceramics
Ceramics biomaterials (bioceramics) can be divided into: 1) inert bioceramics: zirconia, alu-mina, aluminum nitrides and carbon; 2) bioactive ceramics: hydroxyapatite, bioglass, etc.; 3) biodegradable/resorbable ceramics: calcium aluminates, calcium phosphates, etc. The inertness, high compressive strength and good appearance make ceramics attractive for dental crowns. Carbon has been used for heart valves exploiting its high specific strength and blood compatibility. Many bioceramics have been also applied as coating onto metal surfaces including nitrides, diamond like, carbon and more recently bioglasses and hydroxyapatites. A book written by Kokubo can be consulted for further reference on bioceramics [26]. 

5.2. Polymers
The main advantage of polymeric biomaterials over metals and ceramics is the ease of manufacturability to produce various shapes. Polymeric biomaterials can be divided into: 1) non-absorbable such as poly(methyl methacrylate), polyamide or nylon, poly(ethylene), etc.; and 2) absorbable such as poly(glycolide acid) and poly(lactide acid), etc. They can be a bulk (solid or gel) or coating onto metal surfaces with tailored mechanical and physical properties. In recent development, absorbable polymers have been used for drug delivery carriers loaded with a specific drug in the form of coating on for example drug eluting stents. Jenkins has published a book which can be referred for further details on biomedical polymers [27].

5.3. Composite
Bone is an example of composite biomaterials. It is a composite of the low elastic modulus organic matrix reinforced with the high elastic modulus mineral “fibers” permeated with pores filled with liquids. Composites allow a control over material properties whereas a combination of stiff, strong, resilient but lightweight can be achieved all together. Other examples of biomedical composites include: orthopaedic implants with porous structures, dental filler, and bone cement composed of reinforced poly(methyl methacrylate) and ultra-high-molecular-weight poly(ethylene). Further reading on biomedical composites can be found in a book au-thored by Ambrosio [28].


6. Recent Development

6.1. Nickel-free alloys
Elimination of all possibility of toxic effects from leaching, wear and corrosion has become a great concern. Stainless steels have been further developed to be Ni-free by replacing Ni with other alloying elements while maintaining the stability of austenitic phase, corrosion re-sistance, magnetism and workability. This has lead to the use of Nitrogen (N) creating Fe-Cr-N, Fe-Cr-Mo-N and Fe-Cr-Mn- Mo-N systems [4]. The achieved higher strength opens the possibility for reduction of implant sizes where limited anatomical space is often an issue, for example, coronary stents with finer meshes [4].

6.2. Low elastic modulus alloys
In the recent development metallic biomaterials are desired to exhibit low elastic modulus, increased wear resistance and workability. Elastic moduli of Ti-Niobium (Nb) systems such as Ti-29Nb-13Ta-4.6Zr [29] and Ti-35Nb-4Sn [30] can go down to 50-60 GPa which are closer to that of cortical bone (10-30 GPa). Wear resistance of cast Co- Cr alloy has been improved by maximizing C content and addition of Zr and N where optimal precipitation hardening permits the formation of fine and distributed carbides and the suppression of -phase [31]. Improved workability of wrought Co-Cr alloys has been achieved by adding N to suppress carbides and intermetallics [32]. 

6.3. Porous metals
Apart from dense metallic biomaterials, porous structured metals offer further reduction on elastic modulus to get closer to that of cortical bone. This structure can be fabricated through powder sintering, space holder methods, decomposition of foaming agents and rapid proto-typing [33]. A combination of rapid prototyping with investment casting [34], or powder sinter-ing [35], or 3D fiber deposition [36] and or selective laser melting [37] are some of promising process for the development of porous metal structure for biomedical implants. Solid free form fabrication, a mouldless manufacturing techniques or rapid prototyping, have been suc-cessfully used to fabricate complex scaffolds. These technologies allow the preparation of tissue-engineered constructs with a controlled spatial distribution of cells and growth factors, also controlled gradients of scaffold materials with a targeted microstructure [38].


6.4. Metallic glasses
A novel class of metals, metallic glasses, currently attracts attention from biomaterialist [39]. Nickel-free Zr-based bulk metallic glasses represent their interesting  properties where tensile strength, low elastic modulus and corrosion resistance are superior to those of crystalline al-loys [40]. These metals have high resistance to crystallization during cooling that allow the formation of bulk amorphous alloys or bulk metallic glasses [41]. These alloys exhibit unusual combinations of engineering properties such as very high specific strength, and elastic strain limit which some are interesting for biomedical use.

6.5. Biodegradable metals
With recent development in biotechnology, new concept of bioactive biomaterials, rather than inert biomaterials, was raised. A positive interaction of implant with the physiological site is promoted. Some level of biological activity is needed in particular area, such as in tissue engineering, where direct interactions between biomaterials and tissue components are very essential. In particular cases, biomaterials are needed only temporary and are expected to support the healing process and to degrade thereafter. These degradable biomaterials may be defined as materials used for medical implants which allow the implants to degrade in human body environment [5]. Biodegradable/bioabsorbable polymers were the first inves-tigated for use as biomaterials [42]. Meanwhile, the idea of considering biodegradable metals to fabricate temporary implants required in some sort breaking the paradigm where corrosion resistance has always constituted one of the main requirements for metallic biomaterials.

 

7. Regulation on Biomaterials
Finally, to be used clinically a biomaterial must be approved by authoritative bodies such as the United States Food and Drug Administration (FDA) or European conformity (CE) mark-ing. With the FDA, the proposed biomaterial will be
either granted Premarket Approval (PMA) if substantially similar to one used before the 1976 FDA legislation, or has to go through a series of guided biocompatibility assessments. In Malaysia, with the enactment of the MDA 2012, all medical devices must be approved by the Medical Devices Authority, Ministry of Health Malaysia.

 

8. Conclusion
In some applications, ceramics and polymers have been replaced metals owing to their ex-cellent biocompatibility and biofunctionality. However, those require high strength, toughness and durability, are still made of metals. With
additional biofunctionalities and revolutionary use of metal such as for biodegradable implants, metals will continue to be used as biomaterials in the future. The direction goes toward the combination of the mechanically superior metals
and the excellent biocompatibility and biofunctionality of ceramics and polymers to obtain the most desirable clinical performance of the implants.

 

9. References

  1. Sherman WO. Vanadium steel bone plates and screws. Surg Gynecol Obstet 1912;14:629-34.
  2. Habibovic P, Barrère F, Blitterswijk CAV, Groot Kd, Layrolle P. Biomimetic hydroxyapatite coating on metal implants. J Am Ceram Soc 2002;83:517-22.
  3. Lahann J, Klee D, Thelen H, Bienert H, Vorwerk D, Hocker H. Improvement of haemocompatibility of metallic stents by polymer coating. J Mater Sci Mater Med 1999;10:443-8.
  4. Yang K, Ren Y. Nickel-free austenitic stainless steels for medical applications. Sci Technol Adv Mater 2010;11:1-13.
  5. Hermawan H, Mantovani D. Degradable metallic biomaterials: The concept, current developments and future directions. Minerva Biotecnol 2009;21:207-16.
  6. Schneck DJ. The Biomedical Engineering Handbook. Boca Raton: CRC Press; 2000.
  7. Hench LL, Ethridge EC. Biomaterials: The interfacial problem. Adv Biomed Eng 1975;5:35-150.
  8. Black J. Biological Performance of Materials. New York: Plenum Press; 1984.
  9. Niinomi M. Metals for Biomedical Devices. Cambridge: Woodhead Publishing; 2010.
  10.  ASTM. ASTM F 138: Standard specification for wrought 18chromium-14nickel-2.5molybdenum stainless steel bar and wire for surgical implants (UNS S31673). WestConshohocken: ASTM International; 2003.
  11. ASTM. ASTM F 899: Standard Specification for Wrought Stainless Steels for Surgical Instruments. West Conshohocken: ASTM International; 2011.
  12. ASTM. ASTM F 2181: Standard Specification for Wrought Seamless Stainless Steel Tubing for Surgical Implants. West Conshohocken: ASTM International; 2009.
  13. ASTM. ASTM F 75: Standard Specification for Cobalt-28 Chromium-6 Molybdenum Alloy Castings and Casting Alloy for Surgical Implants (UNS R30075). West Conshohocken: ASTM International; 2007. 
  14. ASTM. ASTM F 90: Standard Specification for Wrought Cobalt-20Chromium-15Tungsten-10Nickel Alloy for Surgical Implant Applications (UNS R30605). West Conshohocken: ASTM International; 2007.
  15. ASTM. ASTM F 562: Standard Specification for Wrought 35Cobalt-35Nickel-20Chromium-10Molybdenum Alloy for Surgical Implant Applications (UNS R30035). West Conshohocken: ASTM International; 2007.
  16. ASTM. ASTM F 1537: Standard Specification for Wrought Cobalt-28Chromium-6Molybdenum Alloys for Surgical Implants (UNS R31537, UNS R31538, and UNS R31539). West Conshohocken: ASTM International; 2011.
  17. Brandes EA, Brook GB. Smithells Metals Reference Book. 7th ed. Oxford: Butterworth-Heinemann; 1992.
  18. ASTM. ASTM F 67: Standard Specification for Unalloyed Titanium, for Surgical Implant Applications (UNS R50250, UNS R50400, UNS R50550, UNS R50700). West Conshohocken: ASTM International; 2006.
  19. ASTM. ASTM F 136: Standard Specification for Wrought Titanium-6 Aluminum-4 Vanadium ELI (Extra LowInterstitial) Alloy for Surgical Implant Applications (UNS R56401). West Conshohocken: ASTM International; 2008.
  20. ASTM. ASTM F 2063: Standard Specification for Wrought Nickel-Titanium Shape Memory Alloys for Medical Devices and Surgical Implants. West Conshohocken: ASTM International; 2005.
  21. John C W. Biocompatibility of dental casting alloys: A review. J Pros Dent 2000;83:223-34. 
  22. Wang YB, Zheng YF, Wei SC, Li M. In vitro study on Zrbased bulk metallic glasses as potential biomaterials. J Biomed Mater Res 2011;96B:34-46.
  23. Zberg B, Uggowitzer PJ, Loffler JF. MgZnCa glasses without clinically observable hydrogen evolution for biodegradable implants. Nature Materials 2009;8:887-91.
  24. Williams DF. Definitions in biomaterials. Progress in Biomedical Engineering. Amsterdam: Elsevier; 1987. p. 67.
  25. Park JB, Lakes RS. Biomaterials: An Introduction. 3rd ed: Springer; 2007. 
  26. Kokubo T. Bioceramics and Their Clinical Applications. Cambridge: Woodhead Publishing; 2008. 
  27. Jenkins M. Biomedical Polymers. Cambridge: Woodhead Publishing; 2007.
  28. Ambrosio L. Biomedical Composites. Cambridge: Woodhead Publishing; 2009.
  29. Kuroda D, Niinomi M, Morinaga M, Kato Y, Yashiro T. Design and mechanical properties of new [beta] type titanium alloys for implant materials. Mater Sci Eng A1998;243:244-9.
  30. Matsumoto H, Watanabe S, Hanada S. Beta TiNbSn alloys with low Young’s modulus and high strength.Mater Trans 2005;46:1070-8.
  31. Lee SH, Nomura N, Chiba A. Significant improvement in mechanical properties of biomedical Co-Cr-Mo alloys with combination of N addition and Cr-enrichment. Mater Trans 2008;49:260-4.
  32. Chiba A, Lee S-H, Matsumoto H, Nakamura M. Construction of processing map for biomedical Co- 28Cr-6Mo-0.16N alloy by studying its hot deformation behavior using compression tests. Mater Sci Eng A 2009;513-514:286-93.
  33. Ryan G, Pandit A, Apatsidis DP. Fabrication methods of porous metals for use in orthopaedic applications. Biomaterials 2006;27:2651-70.
  34. Lopez-Heredia MA, Sohier J, Gaillard C, Quillard S, Dorget M, Layrolle P. Rapid prototyped porous titanium coated with calcium phosphate as a scaffold for bone tissue engineering. Biomaterials 2008;29:2608-15.
  35. Ryan GE, Pandit AS, Apatsidis DP. Porous titanium scaffolds fabricated using a rapid prototyping and powder metallurgy technique. Biomaterials 2008;29:3625-35.
  36. Li JP, Habibovic P, van den Doel M, Wilson CE, de Wijn JR, van Blitterswijk CA, et al. Bone ingrowth in porous titanium implants produced by 3D fiber deposition.Biomaterials 2007;28:2810-20.
  37. Hollander DA, von Walter M, Wirtz T, Sellei R, Schmidt- Rohlfing B, Paar O, et al. Structural, mechanical and in vitro characterization of individually structured Ti-6Al-4V produced by direct laser forming. Biomaterials 2006;27:955-63.
  38. Hutmacher DW, Sittinger M, Risbud MV. Scaffoldbased tissue engineering: rationale for computer-aided design and solid free-form fabrication systems. Trends Biotechnol 2004;22:354-62.
  39. Schroers J, Kumar G, Hodges T, Chan S, Kyriakides T. Bulk metallic glasses for biomedical applications. Journal of the Minerals, Metals and Materials Society 2009;61:21-9.
  40. Chen Q, Liu L, Zhang S-M. The potential of Zr-based bulk metallic glasses as biomaterials. Front Mater Sci China 2010;4:34-44. 
  41. Johnson W. Bulk amorphous metal—An emerging engineering material. Journal of the Minerals, Metals and Materials Society 2002;54:40-3.
  42. Stack RS, Califf RM, Phillips HR, Pryor DB, Quigley PJ, Bauman RP, et al. Interventional cardiac catheterization at Duke Medical Center. Am J Cardiol 1988;62:3F-24F.