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Implants and biomaterials
Synopsis
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What is a biomaterial?
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There are many definitions of biomaterials but a widely used one from the National Institutes of Health defines a biomaterial as “any substance (other than a drug) or combination of substances synthetic or natural in origin, which can be used for any period of time, as a whole or part of a system which treats, augments, or replaces tissue, organ, or function of the body”.
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With the advent of tissue engineering and regenerative medicine in recent years, the definition has broadened to include “any material used in a medical device intended to interact with biological systems”, allowing for structures and combination devices that actively interact with the body to be included in the field.
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Biomaterials can be synthetic (i.e., those made by humans) or biological (i.e., those produced by a biological system).
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Further classifications based on development stage or material characteristics are also common but are beyond the scope of this chapter.
Access the Historical Perspective section and Box 31.1 online at Elsevier eBooks+
For the purposes of this chapter, biomaterials will be divided into the following general categories: metals, polymers, cera-mics, glues, skin substitutes, and bioprosthetics.
Metals
To achieve the mechanical and biophysical properties desired for biocompatible applications in medicine, combinations of metals, called alloys, have been developed. These alloys are designed to be inert and withstand the naturally corrosive environment found within the human body. In general, these alloys have mechanical properties that exceed the properties of the natural tissue they are supporting because, unlike natural tissues, they are unable to recover from deformation.
Stainless steel
Stainless steel has been used as a biological implant since the 1920s. Stainless steel was designed to prevent corrosion and consists of over 10 individual compounds which provide it with the desired chemical and mechanical properties. The stainless steels used in medical applications are iron–chromium–nickel alloys with at least 17% chromium ( Table 31.1 ). The chromium creates a protective surface, which contributes to the alloy's anticorrosive properties. The most commonly used stainless steel alloy in medical applications is “316 L”, which, in addition to the chromium composition, has a low carbon content to prevent carbide formation and a high nickel content to increase the strength and hardness of the alloy. Stainless steel has a relatively high tensile strength but is easily deformed (bent). While this is useful in some applications, such as the application of arch bars for maxillomandibular fixation, overall, these mechanical properties are less desirable than other currently available materials such as cobalt–chromium and titanium. In addition, stainless steel can leach metallic ions into the surrounding tissues, causing a severe inflammatory reaction and pain, which may require surgical removal of the implants in some patients. Stainless steel is currently still being used in surgical wire and in arch bars. However, other historically rigid fixation systems that previously utilized stainless steel have now been replaced by other alloys, as detailed below.
Table 31.1
Composition of common metal alloys
Adapted from Holmes RE. Alloplastic materials. In: McCarthy JG, ed. Plastic Surgery . New York: WB Saunders; 1990:698–731.
| Element | Stainless steel (ASTM F138) a | CoCr (ASTM F90) b | Titanium (ASTM F136) c |
|---|---|---|---|
| Weight % | Weight % | Weight % | |
| Chromium | 16–18 | 27–30 | – |
| Nickel | 10–14 | 2.5 max | – |
| Molybdenum | 2–3 | 5–7 | – |
| Carbon | 0.03 max | 0.35 max | 0.08 max |
| Iron | Balance | 0.75 max | 0.25 max |
| Manganese | 2.00 max | 1.00 max | – |
| Phosphorus | 0.045 max | – | – |
| Sulfur | 0.03 max | – | – |
| Silicon | 1.00 max | 1.00 max | – |
| Nitrogen | 0.10 max | – | – |
| Cobalt | – | Balance | – |
| Oxygen | – | – | 0.013 max |
| Aluminum | – | – | 5.5–6.5 |
| Vanadium | – | – | 3.5–4.5 |
| Titanium | – | – | Balance |
a ASTM. Standard specification for wrought 18chromium-14nickel-2.5molybdenum stainless steel bar and wire for surgical implants (UNS S31673). West Conshohocken, PA: ASTM International; 2008.
b ASTM. Standard specification for wrought cobalt-20chromium-15tungsten-10nickel alloy for surgical implant applications (UNS R30605). West Conshohocken, PA: ASTM International; 2009.
c ASTM. Standard specification for wrought titanium-6aluminum-4vanadium ELI (extra low interstitial) alloy for surgical implant applications (UNS R56401). West Conshohocken, PA: ASTM International; 2008.
Cobalt–chromium
Historically, cobalt–chromium alloys have been one of the most significant biomaterials used in humans. Vitallium, a cobalt–chromium–molybdenum (CoCrMo) alloy (ASTM 75), was first described in 1932 to address some of the problems experienced with stainless steel. These alloys replace the iron with cobalt (~60% of the composition), increase the chromium to 25–30% for additional corrosion resistance, and contain 5–7% molybdenum for additional strength (see Table 31.1 ). CoCrMo alloy was used in some of the early craniofacial miniplates and screws and helped to revolutionize that field. The major disadvantage of CoCrMo alloys is the scatter artifact on computed tomography (CT) imaging. Because of this and other benefits, titanium has essentially replaced CoCrMo alloys in most biomedical applications. However, it is still used in dental applications.
Historical perspective
The development of biomaterials has exploded over the past 50 years. In fact, prior to World War II, the term “biomaterial” did not exist. Although there have been reports of biomaterials being used in the form of sutures over 32,000 years ago, most biomaterials have been developed in the last 60 years. The modern era of medical implants might be attributed to a British ophthalmologist, Harold Ridley, in the late 1940s. He noticed that shards of canopy plastic that had been unintentionally implanted in the eyes of Spitfire fighter pilots who had been shot at by enemy machine guns seemed to heal without any adverse reaction. He concluded that the plastic used to make the Spitfire canopy, poly(methyl-methacrylate), might be used to make implant lenses for patients with cataracts. In 1949, he implanted the first artificial lens into a human. This observation and innovation were the precursors to the modern intraocular lenses that are now used over 10 million times per year for patients with cataracts.
Around the same time, several independent groups of surgeons and engineers developed biomaterial-based implants such as vascular grafts, hip replacements, and heart valves. These innovators defined the foundations of biomaterial science in an era before principles for medical materials were established. By the 1950s, as surgeons, engineers, and scientists continued to create these new implant materials, it became clear that there were certain properties that an ideal implant would impart. Cumberland and Scales both described the properties of an ideal implant ( Box 31.1 ). Remarkably, although these criteria were published about 60 years ago, they are still the fundamental properties that all modern biomaterials attempt to achieve.
Box 31.1
Properties of an ideal implant
Modified from Cumberland VH. A preliminary report on the use of prefabricated nylon weave in the repair of ventral hernia. Med J Aust . 1952;1:143–144; and Scales JT. Tissue reactions to synthetic materials. Proc R Soc Med . 1953;46(8):647–652.
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Minimal foreign-body response
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Elastic or supple
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Can be tailored easily
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Good tissue incorporation
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Allows collagen ingrowth
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Promotes permanent tissue repair
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Good tensile strength
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Tolerates infected environment
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Minimal wound complications
Titanium
Titanium alloys were introduced into medical applications in the early 1980s. Since that time, titanium has almost entirely replaced the other alloys in medical applications. This is because the titanium alloys are stronger, lighter, have higher resistance to corrosion, and generally cause less inflammation. Titanium is considered non-immunogenic and chemically inert, generating relatively low levels of foreign body response within the body. Titanium also has less stress shielding (localized osteopenia secondary to the implant protecting the bone from normal loading) than other metal implants because they have less stiffness. Titanium alloys have less than 0.5% iron in them (see Table 31.1 ), which provides them with two additional beneficial properties: they do not set off metal detectors, and they do not create a significant artifact on CT or magnetic resonance imaging studies. Finally, titanium can form chemical bonds with the surrounding mineralized bone without typical fibrous tissue forming between the implant and bone. This unique characteristic allows titanium to be used to create osteointegrated implants. In many cases, pure titanium rather than an alloy is used for medical implants. Plastic surgery applications of titanium include plates and screws for rigid fixation of bone and mesh for use in applications such as orbital wall reconstruction ( Fig. 31.1 ).
Gold
One of the earliest mentions of a biomedical device dates back to ancient Egypt in ~2500 BCE, where loose teeth were fixated with golden wires. Although gold is chemically inert, in its pure form it has poor mechanical properties. Thus, when some strength is needed (for example, in dental fillings), a gold alloy is used. For applications such as eyelid weights in patients with lagophthalmos, where strength is less of an issue, 24-carat gold alloy (99.9% w/w purity) is commonly used to ensure chemical inertness.
Platinum
Like gold, platinum is an inert metal and is the material of choice for patients with gold sensitivity who need an eyelid implant for lagophthalmos. Platinum is denser than gold, thus the eyelid implants have a lower profile and are less noticeable than gold implants.
Some formulations containing platinum have been shown to be immunogenic and thus have raised concerns over long-term exposure. Because the Centers for Disease Control state that short-term exposure to platinum salts may cause irritation of the eyes, nose, and throat, and long-term exposure may cause both respiratory and skin allergies, the current Occupational Safety and Health Administration (OSHA) standard for soluble platinum salts is 2 μg/m 3 of air averaged over 8 hours.
Platinum is also used as a catalyst in the formation of some polymers. Platinum black, a fine powder (1 nm–1 µm) form of platinum, is used in many of these reactions. Platinum black catalyzes the addition of hydrogen to unsaturated organic compounds and is used in the production of silicone gel breast implants (see below).
Platinum complexes have also been used as chemotherapy and show efficacy against some tumors. Cisplatin, the best-known platinum chemotherapeutic agent, has activity against multiple types of cancer. However, it has some significant side effects, including cumulative irreversible kidney damage and deafness.
Polymers
Polymers are molecules composed of repeating subunits. They are typically defined as a backbone series of molecules with side chains that are covalently bound to the backbone molecules. The physical properties of the polymer are defined by the structure of the monomer, the number of monomer units in the polymer chain, and the degree of cross-linking (the amount of bonding between two polymer chains). As polymer chains are cross-linked, the ability for them to move independently is decreased. For example, a polymer with freely flowing chains might initially exist as a liquid; as the amount of cross-linking is increased, this polymer becomes more of a gel or a solid.
Silicone
Silicone is probably the most maligned and misunderstood biomaterial used in medicine today. This is likely due to the controversy revolving around the use of silicone in breast implants. Silicone gel-filled breast implants were first introduced in the US in 1962 and consisted of two shells made of thick, smooth-walled silicone elastomer, filled with a viscous silicone gel material (dimethylsiloxane) and glued together. Multiple variations and modifications to the shell and gel were made over the years in an attempt to improve the outcomes of breast augmentation and reduce the associated complications.
Silicone is a family of polymers consisting of alternating silicon (Si) and oxygen (O) molecules. Table 31.2 shows the nomenclature of silicone. Siloxane, the basic repeating unit of silicone, consists of silicon, oxygen, and a saturated hydrocarbon (alkane) side group. Poly-dimethylsiloxane (PDMS) |(CH 3 ) 2 SiO| n is the polymer used in most medical applications. PDMS is a very pure polymer that consists of the silicone backbone (silicon and oxygen) with two methyl side chains. It is one of the most inert biomaterials available for use in medical devices. Altering the length and molecular weight of the PDMS changes the mechanical properties and behavior of the silicone gel. PDMS molecules with less than 30 monomers are defined as low-molecular-weight formulations and have a viscosity similar to baby oil. High-molecular-weight formulations contain more than 3000 monomers and are solids. Controlling the degree of cross-linking, changing additives, and adjusting the curing process can also modify the mechanical properties of silicone. For example, the silicone gel found in breast implants is cured in a hydrosilation reaction where some of the methyl side chains (CH 3 ) are replaced by vinyl side chains (CH=CH 2 ) that then allow the silicone chains to cross-link with each other. This reaction is catalyzed by platinum and some residual platinum can be found in silicone gel breast implants. The silicone shell on breast implants is made of fully polymerized silicone with an amorphous (noncrystalline) silica filler added for strength ( Fig. 31.2 ).
Table 31.2
Silicone nomenclature
Adapted from Miller MJ, Ogunleye OT. Biomaterials. In: Guyuron B, Eriksson E, Persing JA, et al., eds. Plastic Surgery Indications and Practice . New York: Saunders Elsevier; 2009:57–66.
| Term | Chemical formula | Description |
|---|---|---|
| Silicon | Si | Most abundant element on earth Does not occur naturally in its metallic state |
| Silica | SiO 2 | Sand, marble, or quartz |
| Silicate | Na 2 SiO 3 | In one form, used as a desiccant (e.g., in anesthesia machines) |
| Siloxane | R 2 SiO | Monomer of silicon and oxygen |
| Silicone | |R 2 SiO| n | Polymers of silicon and oxygen |
| Poly-dimethylsiloxane | |(CH 3 ) 2 SiO| n | The building block for most medical-grade silicone products, including breast implants |
In 1988, the US Food and Drug Administration (FDA), out of concerns from reports of implant failure and allegations of resultant complications and illness, relabeled silicone breast implants as class III medical devices and called for data from manufacturers showing the safety and effectiveness of these devices. After an extensive investigation, in 1992, the FDA claimed that there was “inadequate information to demonstrate that breast implants were safe and effective” and placed a moratorium on silicone gel breast implants for cosmetic purposes but allowed their continued use for reconstruction after mastectomy, correction of congenital deformities, or replacement of ruptured silicone gel-filled implants due to medical or surgical reasons.
To further investigate the safety and efficacy of breast implants, the Department of Health and Human Services appointed the Institute of Medicine of the National Academy of Science (IOM) to begin one of the most extensive research studies in medical history. Their charge was to examine potential complications during or after silicone-based breast implant surgeries. In 1999, after reviewing years of evidence and research concerning silicone gel-filled breast implants, the IOM released a comprehensive report on both saline-filled and silicone gel-filled breast implants entitled Safety of Silicone Breast Implants . The IOM found that “evidence suggests diseases or conditions such as connective tissue diseases, cancer, neurological diseases or other systemic complaints or conditions are no more common in women with breast implants than in women without implants”. Most individual studies and all systematic review studies have also subsequently failed to find a link between silicone breast implants and disease. In 2006, the FDA lifted its ban and other restrictions on the use of silicone gel-filled breast implants produced by the two manufacturers for breast reconstruction and for cosmetic breast augmentation. The end to this ban required a complete 10-year study on women who had already received the implants, along with an additional 10-year study on the safety of the devices in 40,000 women. It was also mandated that patients be given brochures explaining the potential risks of breast implants.
Other plastic surgery applications of silicone include facial implants for malar, nasal, and chin reconstruction or augmentation, and orbital floor reconstruction. Hand surgeons use silicone implants for arthroplasty, flexor tendon replacement, and bone block spacers. Silicone is beneficial in these applications because it is relatively inert, malleable, and deformable. Low-molecular-weight silicone was also used in the past as an injectable soft-tissue filler, although it has become obsolete due to severe tissue reaction and migration.
Silicone is probably the most studied implantable material available today. After over 35 well-conducted studies from many countries, there is no conclusive evidence that this material causes disease. Furthermore, medical-grade silicone is ubiquitous, being found in more than 1000 medical products as either a component or as a residuum from the manufacturing process. For example, every disposable needle and syringe, as well as intravenous tubing, is lubricated with silicone. Medications in stoppered vials contain residual silicone from its use in the manufacturing process. Silicone elastomers, in their solid form, are used for pacemaker coatings, tubing, prosthetic joints, hydrocephalus shunts, and various facial and penile implants. Like breast implants, some testicular and chin implants are made of a silicone gel in a silicone envelope.
Silicones are also found in some medications. If a medication contains an ingredient with the name “methicone” (e.g., simethicone), this is a silicone that has been modified for human consumption. Silicones are also used in household items such as lipstick, suntan/hand lotion, hairspray, processed foods, and chewing gum. Medical-grade silicones invoke a nonspecific foreign body response, resulting in typical macrophage invasion, giant cell formation, and eventual scarring. Extensive investigations by several scientific bodies (e.g., the IOM and the UK Department of Health) have failed to show that systemic illness is definitively attributed to silicones.
The next progression in silicone gel breast implants was the approval by the FDA of cohesive gel implants. The silicone within cohesive gel implants is extensively crosslinked and retains its shape even in the event of implant rupture. These implants are also unique in terms of their shape, which is designed to more closely resemble the natural contours of the breast. All three breast implant manufacturing companies have received approval for their cohesive gel implants: Sientra (Santa Barbara, CA) in March 2012; Allergan (Irvine, CA) in February 2013; and Mentor (Irvine, CA) in June 2013.
Silicone shell texturing
The outer elastomer shell surface of silicone breast implants may harbor varying degrees of roughness ranging from smooth to macrotextured. The most widely recognized classification to characterize the degree of surface texturing is the International Organization for Standardization (ISO) 14607:2018, which classifies surfaces based on their average roughness as either smooth (<10 µm), microtextured (10–50 µm), or macrotextured (>50 µm). The late 1980s saw the advent of breast implant shell texturing via a variety of processes including “salt-loss” and “imprint stamping”. Surface texturization was thought to allow for tissue in-growth and improved adherence to the host tissue, thus minimizing instances of implant rotation within the pocket compared to smooth surface breast implants. Further, textured implant shells were postulated to reduce capsular contracture on the assumption that an irregular surface would mitigate a parallel orientation of deposited collagen fibers, which has been associated with contracture in smooth implants. Brands such as Allergan (BIOCELL surface) and others began producing “salt-loss” texturization by applying salt crystals onto the silicone shell prior to curing, which was removed afterwards by rinsing. This process imparts a coarse and granular texture onto the implant surface. Other textured implant types such as Mentor’s (Siltex surface) utilized an imprint-stamping technique that generates a much finer and homogenous outer surface texturization. .
Recently, the purported benefits of textured implants have been called into question. Reports outlining late seromas, rippling, double capsules, increased bacterial growth and infection, capsular contracture, and implant rotation have been reported, particularly in macrotextured implants. Some long-term retrospective studies have demonstrated minimal differences in capsular contracture occurrence rates between textured and smooth implants. Furthermore, recent clinical studies have reported that textured breast implants produce distinct host responses compared to their smooth counterparts. Of note, textured implants have been linked to the onset of a hematological malignancy termed breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a CD30-positive, ALK-negative T-cell origin non-Hodgkin’s lymphoma, typically presenting with a late-onset peri-implant effusion.
Based upon a series of case reports which followed a sentinel case reported in 1997, the FDA issued a safety communication in January of 2011 stating, “women with breast implants may have a very small but increased risk of developing anaplastic large cell lymphoma (ALCL) in the scar capsule adjacent to the implant”. At the time of the communication, the FDA was aware of approximately 60 cases of breast implant patients who had developed ALCL out of the approximately 5–10 million women who had received breast implants worldwide. Since then, over 1150 women worldwide have been diagnosed with breast implant-associated ALCL (BIA-ALCL) and the incidence continues to increase. Most strikingly, this malignancy has only been observed in patients with textured surface implants. In July of 2019, the FDA ordered a class I voluntary recall of all Allergan textured devices from the market due to the risk of BIA-ALCL. Currently there exists general consensus that a relationship between textured breast implants and BIA-ALCL does exist and that the risk is higher in macrotextured devices. These macrotextured devices have been linked to chronic inflammation, and studies on animal models support this by reporting the highest severity of foreign body response and inflammation in textured devices with roughness >80 µm.
A causal link between textured implants, chronic inflammation, and development of BIA-ALCL has yet to be established. However, several hypotheses have been put forth, including increased biofilm development, shell shedding of particulates leading to perpetual exhaustive phagocytosis and cytokine release by macrophages, or increased mechanical shear and friction stresses at the implant–tissue interface leading to an overt inflammatory response in textured devices. In the US, the use of textured implants has dropped precipitously as many surgeons have abandoned using textured implants altogether, switching instead to smooth devices in their practices. As the incidence of BIA-ALCL is expected to continue to increase, it is essential for plastic surgeons to be made aware of this disease entity. Further studies are needed to determine the molecular mechanisms driving the development and disease progression of BIA-ALCL, as well as establish appropriate standards of care and prevention. Understanding how the surface properties of textured implants affect inflammatory cell response will allow for the rational design of next generation implants that minimize long-term complications while achieving an optimal aesthetic outcome.
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