Historical Overview of Materials

The history of mankind has been marked by the evolving use of natural and man-made materials. The prehistoric or Paleolithic era (“palaois” = old, “lithos” = stone) was followed by the Neolithic revolution (8000 BC) which led to the development of agriculture. The first civilizations emerged in Mesopotamia between the Euphrates and Tigris rivers. There people began building tools to work the land. They also addressed their medical needs by developing rudimentary medical therapies, including medical devices applied externally or even implanted into the body.

These “biomaterials” for the earliest medical devices were initially simple and were implanted without knowledge of whether they were even biocompatible. A carbon-based material implanted in the skin (“a tattoo”) has been found dating to 5000 BC. By 3200 BC there is evidence of the first suture usage.

The development of metallurgy with the first use of copper gave rise to a period known as the “bronze era,” accelerating the rate at which humans gained control over nature. By developing techniques to manipulate metals – molding, heating, cracking, and alloy development – more advanced tools were created.

By 2000 BC, the Aztecs and Chinese used gold for dental applications. By 1065 BC, the Egyptians built wooden artificial digits to replace lost fingers. By 200 BC, metallic sutures using gold were described, and by 60 AD the Mayans used sea shields as rudimentary dental implants.

Biomaterials: Definition and Classification

A biomaterial can be defined as “a material intended to interface with biological systems for evaluating, treating, augmenting, or replacing a tissue or organ.” A biomaterial is thus any substance brought into contact with living tissue for the purpose of treating a medical or dental condition. Biomaterials are usually synthetic and are continuously or intermittently in contact with body fluids (AZO materials). Typically, surgical instruments and dental instruments are not categorized as biomaterials. The materials used for external prostheses, such as artificial limbs and hearing aids, are also not considered biomaterials most of the time.

The evolution of biomaterials can be conceptually divided into four generations:

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  Generation I: Use of inert materials

  
  
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  Generation II: Introduction of interactive biomaterials

  
  
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  Generation III: Introduction of viable biomaterials

  
  
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  Generation IV: Use of tissue engineered/genetic-engineered tissues.

Generation I involved using inert materials intended not to harm. Generation II involved materials intended to provide a benefit in addition to the “not to harm” approach of generation I. Generation III involved the use of materials capable of acting as scaffolds where biological tissue could adhere to the biomaterial to induce tissue growth. Generation IV involves the use genetic engineering and tissue-engineering techniques to build up tissues specifically designed for the host. This is to avoid any unwanted inflammatory or immunological response caused by the biomaterial. In other words, there is matching of the receptor (host) histocompatibility profile with the histocompatibility profile of the donor (biomaterial) using genetic-engineering techniques.

For a biomaterial to be effective it must be compatible with tissues chemically and mechanically (Table 2.1a). Biomaterials should have adequate strength for resisting fatigue – so-called mechanical compatibility. They should be chemically inert and stable – so-called chemical compatibility, and they should not elicit allergenic, carcinogenic, immunogenic, or toxic reactions – so-called pharmacological compatibility.

There are many ways to classify biomaterials. They can be considered either synthetic (man-made) or natural. They can be classified according to their expected duration inside the body (permanent or transient). They are frequently categorized according to their tissue usage (in soft tissue, in hard tissue, or in the blood). They are probably most frequently categorized according to the medical discipline involved in their use. In this regard, the present discussion will center most on the orthopedic applications for biomaterials, but it should be recognized there are important and widespread biomaterial applications for cardiovascular, dental, ophthalmologic, neurosurgical, otolaryngologic, and pediatric conditions.

Implant is a generic term used for any material or device placed in vivo for the treatment of a medical or dental condition. A prosthesis is an artificial substitute for a missing body part. Sometimes the terms prosthesis, implant, and medical device are used interchangeably.

Early biomaterials were naturally found substances that seemed to be compatible with human and animal tissues. They were materials found commonly in nature or in the laboratories of physicians and experimenters. There was little knowledge and consideration of their physical and chemical properties. These substances included gold, iron, brass, glass, wood, and bone, most of which did not function well due to their ultimate poor tissue compatibility and the lack of aseptic techniques used in the early days of implant placement with resultant infections and sepsis. Before the concept of asepsis introduced by Lister and advanced during the American Civil War, various metal wires and pins made of iron, steel, gold, copper, silver, and platinum could not be evaluated properly because of infection, which masked the true effects of these materials on tissues (Park, 1994).

In the 1930s, non-corrosive metal alloys (stainless steel and cobalt chromium) combined with an understanding of tissue response to foreign materials made possible the first useful biomaterial applications in medicine and dentistry. In the 1940s, plastics were introduced for biomechanical uses. One of the early plastics was an acrylic, poly(methyl methacrylate) (PMMA), used for a total hip prosthesis. PMMA is also used to fabricate corneal implants and is noted for its reasonable mechanical strength, high refractive index, and good biocompatibility.

Successful open-heart surgical techniques led to the introduction of artificial blood vessels in the 1950s, and commercial artificial heart valves became available in the 1960s. Since then, there has also been the widespread development of biomaterials for orthopedics including joint prostheses, fracture fixation plates, screws, rods, vertebral fixation apparatus, bone substitute materials, and joint surface materials. There has also been widespread introduction of biomaterials for use in coronary artery stents, vascular grafts, cardiac pacemakers, intravenous and central venous catheters, breast implants, drug delivery systems, intraocular lenses, and deep brain stimulation electrodes just to name a few applications for materials in medicine and dentistry.

Table 2.1b provides comparison of the mechanical properties of human tissues and implant materials for a quick reference. As one might expect, metals and ceramics are primarily used for constructing implants that bear a large load, whereas elastomers (rubbers), plastics, and carbons are used largely for soft-tissue replacements and for tubes, drains, and catheters. Recently, composite materials are being considered for fabricating implants. One should be careful not to generalize concerning the use of implant materials, because soft materials may also be used for hard-tissue applications, such as silicone rubber for toe and finger joint replacements and polyethylene for the acetabular cup in hip joint replacement.

Types of Corrosion

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  Galvanic corrosion: An implant with two different metals separated by an ionic solution can have galvanic currents (ion flows) that lead to corrosion.

  
  
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  Pitting corrosion: A small hole in an implant material may create an anodic region which leads to an electrical current between it and cathodic regions in the material.

  
  
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  Crevice corrosion: Corrosion taking place in a confined space (crevice).

  
  
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  Intergranular corrosion: Corrosion that occurs where different metals meet at the boundaries between grains.

Host Response

The host response to biomaterials in medical implants is executed by the two main arms of the immune system, namely the innate response and the adaptive response. Both systems operate through a temporal sequence of events including an acute response, subacute response, subchronic response, and chronic response.

Another way to characterize the host response to biomaterials is to define the following stages:

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   1. Injury (implantation)

   
   
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   2. Provisional matrix formation

   
   
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   3. Wound healing

   
   
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   4. Foreign body reaction

   
   
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   5. Encapsulation

From a temporal point of view, it is possible to describe the following phases:

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  First 24 hours after implantation: Migration of neutrophils to the implant site is the hallmark of this stage. The response is mainly due to the wound produced by the implantation rather than the implant material itself.

  
  
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  24 hours–7 days after implantation: Granulation tissue is formed to close the wound generated by the implant. This tissue involves neovascularization.

  
  
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  > 7 days to 1 month: Subchronic phase.

  
  
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  > 1 month–chronic phase: In this phase, capsule formation takes place around the implant. This capsule is made of collagen fibers and isolates the implant from the rest of the body. The capsule can have beneficial or detrimental effects according to how it affects the implant performance.

The resolution of the host response and the material response can lead to one of the following outcomes:

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  Extrusion: Formation of a pocket between the implant and epithelial tissues. This can result in externalization or extrusion of the implant.

  
  
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  Resorption (for resorbable implants): The implant site resolves to a collapsed scar.

  
  
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  Integration: This includes osseointegration, no capsule formation, and normal tissue integrated with the implant.

  
  
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  Encapsulation: Capsule formation. If the capsule is mineralized, it is known as a sequestrum.

Stainless Steels

Steel is an alloy of iron and other elements (often carbon). Steel is widely used in construction and multiple other applications because of its high tensile strength and relatively low cost. Stainless steel is a steel alloy with a minimum of 11% chromium content by mass. Stainless steel is known for its resistance to corrosion and rusting compared to ordinary steel.

The first stainless steel used for biomaterial implant fabrication was type 18-8 (18% Ni–8% Cr) or type 302 in modern classification of the stainless steels. Later, a small amount of molybdenum (2%–4%) was added to improve its corrosion resistance in salt water (Park, 1994). Stainless steel 316L is commonly used in orthopedics. Stainless steel 304 is also regarded as one of the most suitable materials for biomedical applications, and it contains 18%–19.5% Cr, 8.0%–10.5% Ni, and lesser amounts of carbon, manganese, silicon, phosphorus, sulfur, and nitrogen (AZO Materials).

Cobalt–Chromium Alloys

Cobalt–chromium (CoCr) alloy compositions vary considerably. They contain cobalt, chromium, and often molybdenum. A small amount of molybdenum (Mo), for example, in a cast alloy decreases the grain size during solidification, which increases its strength. The mechanical properties of cobalt–chromium alloys are better than those of the stainless steels, and they have excellent corrosion and fatigue resistance (Park, 1994; Saini et al., 2015).

Cobalt–chromium alloys come in two main types, a cast alloy and a wrought alloy. The cast alloy has a high rate of hardening and cannot be contoured at the time of surgery. Cast cobalt–chromium alloy is used for implants having a fixed configuration, such as a total hip prosthesis. The casting procedure is the “lost-wax” technique in which one has to control the alloy grain size and its distribution by controlling solidification temperature, mold surface, and the presence of other elements (such as molybdenum) to achieve a homogeneous solid solution (Park, 1994; Smith, 1985).

The wrought cobalt–chromium alloy is composed mainly of cobalt, chromium, nickel, and tungsten. It has a lower rate of work hardening than the cast alloy. The wrought alloy (Vitallium) is somewhat less resistant to device corrosion than the cast cobalt–chromium–molybdenum alloy (Smith, 1985).

Titanium and its Alloys

Titanium and its alloys have high corrosion resistance and relatively low density (4.5 g/cm³ compared with 7.9, 8.3, and 9.2 g/cm³ for stainless steel and for cast and wrought cobalt chrome alloys, respectively). The excellent corrosion resistance of pure titanium is attributable to the tenacious oxide film (TiO₂) on the surface, similar to aluminum oxide (Al₂O₃), which protects the aluminum surface from further oxidation. Unlike aluminum oxide, titanium oxide film is very stable in saline solution at room temperature (Park, 1994).

Titanium has excellent biocompatibility, but pure titanium does not have sufficient strength for bone replacement. Titanium is often used for biologic purposes by being alloyed with other elements – aluminum, vanadium, manganese, silicon, molybdenum, and tin (Park, 1994). Titanium may be used for sintered beads and fiber mesh coating in total hip and knee arthroplasty (Matassi et al., 2013).

A shape-memory alloy (SMA) remembers its original shape. When deformed, it returns to its pre-deformed shape when it is heated. One SMA is nitinol (Ti–Ni alloy), which has been used for implant applications since the 1960s and has shown good biocompatibility. This alloy allows the production of an implant that can be changed to a desirable body form by a well-controlled heating process. The transformation temperature can be manipulated by controlling the relative amount of titanium in the alloy or by adding small amounts of other metals, such as cobalt. Most importantly, the alloy can be reverted to its original structure by further heating (Park, 1994).