PRINCIPLES, TECHNIQUES, AND BASIC SCIENCE
CHAPTER 7 IMPLANT MATERIALS
TIMOTHY W. KING
While autogenous tissues are often the first choice, implant materials have wide application in plastic surgery including reconstruction or augmentation of soft-tissue defects, bony deformities, or the fixation of fractures. Selecting the implant material depends on the specific requirement for its application. For example, tissue ingrowth into a polypropylene mesh or the rigid incorporation of a bone substitute is often desirable, while the encapsulation (or lack of tissue ingrowth) of a silicone Hunter rod allows for free gliding of a subsequent tendon graft.
Autologous tissue may be more appropriate in many clinical scenarios including patients with a history of radiotherapy, marginal blood supply of the surrounding tissue, or tenuous soft-tissue coverage over the implant. In these cases, the risk of implant-related complications, including infection and implant extrusion, is significant, and the use of an alloplastic implant should be avoided if possible.
Implant materials, however, can be used as alternatives to autogenous tissue in selected cases and in specific situations are superior to autogenous tissue. Implant materials can be created to undergo no resorption and are preferable to autologous grafts that will resorb when used as onlay grafts. For example, implants have been successfully used as bone graft substitutes in orbital floor reconstruction, cranioplasty, and maxillofacial reconstruction. They have the advantage of avoiding operative time for graft harvesting and the absence of donor site morbidity.
The first recorded use of an artificial material can be traced to 30,000 B.C. where these materials were used as sutures. The first recorded implant was thought to date back to 3,000 B.C. where pre-Incan Peruvians used materials such as gold, silver, or nut shells to repair trephination defects. However, recent investigations have brought these reports into question. Regardless, over the next 5,000 years, implant use was sporadic and limited by infection and foreign body reaction. The modern era of medical implants is often attributed to British ophthalmologist Harold Ridley who noted that Spitfire canopy plastic unintentionally implanted in the eyes of pilots healed without adverse reaction. Based on this finding he developed and implanted the first artificial lens into a human in 1949. As surgeons, engineers, and scientists continued to create new implant materials, it became clear that there were certain properties that an ideal implant would impart. Cumberland1 and Scales2 described the properties of an ideal implant, which are shown in Table 7.1. Remarkably, although these criteria were published almost 60 years ago, they are still the fundamental properties that manufacturers of modern biomaterials attempt to achieve.
For the purpose of this chapter, implant materials will be divided into the following general categories: metals, polymers, ceramics, glues, skin substitutes, and bioprosthetic meshes (Table 7.2).
In order to achieve the mechanical and biophysical properties desired for applications in medicine, combinations of metals (alloys) have been developed. These alloys are designed to be inert and withstand the corrosive environment within the human body. Since metals cannot repair themselves after deformation or fatigue, they must have mechanical properties that exceed the properties of the natural tissue they are supporting or replacing (i.e., the metal must be both stronger and stiffer than the natural tissue).
Stainless steel has been used as a biological implant since the 1920s. Medical-grade stainless steel, alloys of iron–chromium–nickel, have a relatively high tensile strength but are 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 leaches metallic ions into the surrounding tissues, causing an inflammatory reaction and pain. Stainless steel is currently used in surgical wire and in arch bars. In the past, bone fixation systems utilized stainless steel, but other alloys have replaced stainless steel in this application.
Historically, cobalt–chromium alloys have been one of the most significant biomaterials used in humans. Vitallium, a cobalt–chromium–molybdenum (Co-Cr-Mo) alloy, was first described in 1932 to address some of the problems experienced with stainless steel. Co-Cr-Mo alloy was used in early craniofacial miniplates and screws and revolutionized the field. The major disadvantage of Co-Cr-Mo alloys is the scatter artifact on computed tomography (CT) imaging. Because of this, and other benefits, titanium has essentially replaced Co-Cr-Mo alloys in most biomedical applications.
Commercial-grade medical titanium implants were introduced in the early 1980s and have almost entirely replaced the other alloys in medical applications because they are stronger, are lighter, have higher resistance to corrosion, and cause less inflammation. Titanium also has less stiffness, which results in less stress shielding (localized osteopenia secondary to the implant protecting the bone from normal loading). More recently, some companies have also introduced titanium alloy implants. The alloys are stronger than the pure titanium, allowing for thinner plates without compromising their overall strength. Pure titanium or titanium alloys (which have less than 0.5% iron) have 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 fibrous tissue forming between the implant and the bone. This unique characteristic allows titanium to be used to create osseointegrated implants. Plastic surgery applications of these alloys include plates and screws for fixation of bone and titanium mesh for use in applications such as orbital wall reconstruction (see Figure 7.1).
Figure 7.1. Titanium plates for midface reconstruction. L-shaped and curvilinear 2.0 mm plates with a 7, 5, and 3 mm length 2.0 mm screw (left to right).
Although gold is chemically inert, it has poor mechanical properties in its pure form. When strength is required (for example, in dental fillings), a gold alloy is used. For applications such as eyelid weights in patients with lagophthalmos, where strength is not an issue, 24-carat gold alloy (99.9% w/w purity) is used to ensure chemical inertness.
Platinum is an inert metal and is the material of choice for patients with gold sensitivity in need of eyelid implants for lagophthalmos. Platinum has a higher density than gold, thus the eyelid implants have a lower profile and are less noticeable than gold implants. Some formulations containing platinum, however, have been shown to be immunogenic and have raised concerns about long-term exposure. Platinum is also used as a catalyst in the formation of some polymers, including the production of medical-grade silicone used in gel breast implants.
Polymers are molecules composed of repeating monomer subunits. The physical characteristics of a polymer are defined by the structure of the monomer, the number of monomer units in the polymer chain, and the degree of cross-linking. As polymer chains are cross-linked, the ability for them to move independently is decreased. Thus, a polymer with little cross-linking might exist as a liquid while the same polymer with abundant cross-linking becomes a “gel” or “solid.”
Silicone is likely the most maligned and misunderstood implant material today secondary to its use in breast implants. Silicone gel–filled breast implants were first introduced in the United States in 1962. 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. In 1992, the U.S. Food and Drug Administration (FDA) stated 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.3 The Department of Health and Human Services (HHS) subsequently appointed the Institute of Medicine (IOM) of the National Academy of Science to begin one of the most extensive research studies in medical history. In 1999, the IOM released a comprehensive report on both saline-filled and silicone gel–filled breast implants finding 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.”3
In 2006, the ban imposed by the FDA was lifted. As part of the approval process, the FDA required the two approved manufacturers to perform a 10-year study on the safety of the devices in 40,000 women.3 Extensive investigations by several prestigious scientific bodies (e.g., the IOM4 and the British Ministry of Health5) have failed to show that systemic illness is associated with silicones. For a discussion of the recently described anaplastic large cell lymphoma in breast implant recipients, please see Chapter 53.
With all of this research into “silicone” one might ask “what exactly is silicone?” Silicone is a family of polymers consisting of alternating silicon (Si) and oxygen (O) molecules. Poly-dimethylsiloxane (PDMS), the polymer used in most medical applications, is made up of the silicone backbone 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 PDMS can change the mechanical properties and behavior of the silicone gel. Low-molecular-weight PDMS (<30 monomers) has a viscosity similar to baby oil, while high-molecular-weight formulations (>3,000 monomers) are solids. Other methods of altering the mechanical properties include controlling the degree of cross-linking, changing the additives, and altering the curing process. For example, the silicone gel used in breast implants is cured in a hydrosilation reaction where some of the methyl side chains (CH3) are replaced with vinyl side chains (CH“CH2), which then allows the silicone chains to cross-link with each other. The silicone shell of a breast implant consists of fully polymerized silicone and an amorphous (noncrystalline) silica filler added for strength.
Medical-grade silicone is ubiquitous, being found in more than 1,000 medical products as a component or as a residuum from the manufacturing process. For example, every disposable needle, syringe, and 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 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. Ingredients with the name “methicone” (e.g., simethicone) are silicones that have 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 macrophage invasion, giant cell formation, and eventual scarring.
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 used in the past as an injectable soft tissue filler but is not FDA approved for medical use. This application should be avoided because it can cause tissue reactions or migrate.
Polytetrafluoroethylene (PTFE) also known as Teflon was accidentally invented by Roy Plunkett in 1938 while he was trying to develop a refrigerant. It consists of a carbon backbone with fluorine side chains. Expanded PTFE (ePTFE or Gore-Tex) was created by Bob Gore in 1969. It is very chemically stable, cannot be cross-linked (which makes it flexible), and has a non-adherent surface. It has been used for a wide variety of applications from hiking boots to coatings on frying pans. Within the medical field it is used for vascular grafts, as a mesh for abdominal wall reconstruction, and as implants for facial augmentation.
Polyester contains an ester functional group in its main chain. Mersilene is a knitted polyester mesh for use in herniorrhaphy. Polyester mesh is softer and more hydrophilic than polypropylene and in animal studies has shown better tissue ingrowth. Dacron is another form of polyester that has been used for vascular grafts.
Polypropylene has a carbon backbone and side chains of hydrogen and methyl groups. It has been used in hernia and pelvic organ prolapse repair, but polypropylene mesh can erode through the soft tissues over time. Therefore, the FDA has issued warnings on the use of polypropylene mesh in pelvic organ prolapse. It is also used as suture material because of its strength and low foreign body reaction within the body.
Polyethylene consists of a carbon backbone with hydrogen side chains (ethylene). A high-density porous form of polyethylene (Medpor) is used for facial implants (see Figure 7.2). The porosity allows for tissue and vascular ingrowth. It can also be carved to customize the implant for individual patients. The implants are more difficult to place than the ePTFE implants because they are firmer and stiffer. In addition, the soft-tissue ingrowth makes the implant more difficult to remove. Porous polyethylene alone or in combination with titanium mesh is available for reconstruction of the orbital floor. One of the disadvantages of polyethylene alone for orbital floor reconstruction is that the implant is not visualized on CT scans, making it difficult to evaluate implant position.
FIGURE 7.2. High-density porous polyethylene (Medpor) implants for facial augmentation.
Polymethylmethacrylate (PMMA) is a high-molecular-weight polymer commonly used as a replacement for bone. The final product is created by adding liquid methylmethacrylate monomer to powdered methylmethacrylate polymer, which then forms a moldable putty. The monomer polymerizes, binds with the polymer particles, and hardens in about 10 minutes. The polymerization process is an exothermic reaction, which generates high temperatures. Saline irrigation is used to cool the surrounding tissues during the curing process to avoid local tissue damage such as bone necrosis or soft-tissue injury. Applications in plastic surgery include cranial bone reconstruction. PMMA can be used alone or in combination with wire or mesh reinforcement. The immobility and relatively low stresses intrinsic to the calvarium contribute to the low morbidity of PMMA cranioplasty.
Biodegradable polymers were developed to overcome some of the disadvantages associated with permanent implants. Most biodegradation occurs through a combination of chemical reactions, such as hydrolysis or oxidation, and biological processes (e.g., enzymatic or cellular). Both the biodegradable polymer and all of its breakdown products must be biocompatible.6 Although there are a multitude of materials that will degrade in vivo, there are only a few that are clinically relevant as biodegradable polymers. α-Hydroxy acids, specifically poly (lactic acid), poly (glycolic acid) (PGA) and combinations, or copolymers, of these individual polymers known as poly (lactic-co-glycolic acid) (PLGA) are the most common biodegradable polymers used in clinical applications. These polymers degrade through hydrolysis, ending in lactic or glycolic acid. Surgeons are familiar with this polymer as it is used to make Vicryl (Polyglactin 910; Ethicon, Somerville, NJ) sutures. These polymers have been used to create a biodegradable mesh for use in abdominal wall reconstruction and plating systems for craniofacial or hand applications as well as in the fabrication of resorbable scaffolds for tissue engineering and regenerative medicine applications.
The rate of degradation can be modified by altering the ratios of lactic to glycolic acid, adding carbon fibers or other polymers. In general, increasing the concentration of lactic acid decreases the rate of degradation. Manufacturers modify the ratio of lactic and glycolic acid, as well as the specific manufacturing protocol, to optimize the degradation rate and strength of the polymer. For example, LactoSorb (Biomet, Warsaw, IN) consists of 82% poly-L-lactic acid and 18% PGA, while Resorb-X (KLS Martin, Jacksonville, FL, used in the SonicWeld system) is 100% poly-D, L-lactic acid. The Endotine products (Coapt Systems, Inc., Palo Alto, CA) have the same formulation as LactoSorb. At implantation, their strength is equal to that of titanium plating and then decreases with time. Typically their structural integrity is preserved for the first 8 weeks to allow for bony healing to occur.
Medical applications of ceramics were developed in the 1960s. Ceramics have a crystalline structure and are made up of inorganic, nonmetallic molecules. They have some appealing physical properties for biomedical use including decreased foreign body response, resisting bacterial colonization, a high compressive strength, and tissue ingrowth into porous materials (100 µm pore size for bone and 30 µm pore size for soft tissue). However, their benefits are overshadowed by their weaknesses, namely they are brittle and easily fracture under tensile, torsional, or bending loads. Their main uses in plastic surgery are for bone augmentation and replacement. Calcium phosphates are the most common ceramics used in plastic surgery. In addition, calcium phosphates have been shown in the laboratory to be both osteoinductive and osteoconductive, but this has not been demonstrated in the clinical setting.
Calcium phosphates come in two formulations for medical use: hydroxyapatite (Ca10(PO4)6(OH)2) and tricalcium phosphate (Ca3(PO4)2). Tricalcium phosphate has a faster rate of resorption and replacement by bone when compared with hydroxyapatite. They are available as granules for injection and as blocks (both solid and porous), and hydroxyapatite is also available as a cement paste. These implants are commonly used to reconstruct non–load-bearing bones of the face and cranium. The cement paste is beneficial in select cases, such as a cranioplasty, because it is malleable and can be molded during the case. For a discussion on dermal and soft-tissue fillers, please see Chapter 42.
ADHESIVES AND GLUES
Fibrin Tissue Adhesives
The first fibrin tissue adhesive was described in 1944 and was used to aid in the adherence of skin grafts to the recipient tissue bed. Fibrin sealants consist of two parts: fibrinogen and thrombin derived from screened donors. A small amount of factor XIII and calcium is included to catalyze the reaction and form polymerized fibrin. The strength of the fibrin glue is directly proportional to the concentration of fibrinogen in the mixture, while the rate of polymerization is regulated by the concentration of the thrombin. Plastic surgery applications for fibrin sealants include brow lift, facelift, abdominoplasty, the latissimus dorsi donor site, DIEP/TRAM flap donor sites, and chronic seromas.
Cyanoacrylates were accidently discovered in 1942 by Dr. Harry Coover and were marketed as “super glue.” During the Vietnam War, surgeons saved many lives after they discovered that spraying cyanoacrylates over open wounds would stop bleeding and allowed injured soldiers to be transported for treatment.
The exothermic polymerization begins when the cyanoacrylate is exposed to moisture (there is enough moisture in the air to allow polymerization to occur). Applications in plastic surgery include skin closure. The superficial layer of the skin, where the product is applied, has no sutures to hold it together so it is important to approximate the deep layers and provide a tension-free abutment of the two sides. Studies comparing traditional suturing to octyl-2-cyanoacrylate showed that the outcomes were equivalent.7
Over the past two decades, bioengineered skin substitutes have become a mainstream therapy for wound management. Originally designed to replace skin grafts for patients with severe burns, they are now also used in the treatment of chronic venous and chronic diabetic ulcers. It is likely that applications for these products will broaden as they become more advanced. The ideal skin substitute would8:
• Adhere to the wound bed rapidly
• Recapitulate the physiologic and mechanical properties of normal skin
• Be inexpensive
• Avoid immune rejection by the host
• Be highly effective in accelerating tissue regeneration and wound repair
A variety of cells, mediators, and polymers have been tested in various combinations to engineer cultured skin substitutes.9 We review the most common of these below and in Chapter 3.
Integra (Integra LifeSciences Corporation, Plainsboro, NJ) is a bilayer skin substitute consisting of a “dermal” (lower) layer (bovine collagen base with the glycosaminoglycan chondroitin-6-sulfate) and a silicone sheet (upper) layer.10 As the wound heals, the dermal layer is replaced with the patient’s own cells. The silicone sheet, which acts as a temporary epidermis, is removed and a thin split-thickness skin graft is applied to the neo-dermis. Integra is used in complex wounds such as partial or full thickness burns and multiple types of ulcers. Studies evaluating the efficacy of Integra showed that it has a higher infection rate compared with autograft, allograft, or xenograft, but appeared to have a faster rate of wound healing time.10 Integra can also be used in wounds where a skin graft would not adhere.10The neo-dermis will attach to the underlying bed, vascularize over 2 weeks, and then will allow adherence of a split-thickness skin graft.
Epicel (Cultured Epidermal Autografts)
Epicel (Genzyme, Cambridge, MA) is a cultured epidermal autograft grown from the patient’s own keratinocytes derived from a small skin biopsy. The keratinocytes are grown in a co-culture with fibroblasts. Once the keratinocytes are 2 to 8 cell layers thick, the approximately 50 cm2 autograft is attached to a petrolatum gauze backing with stainless steel surgical clips and applied to the patient.
Epicel is used in patients with deep dermal or full thickness burns involving a total body surface area of ≥ 30%. It can be used with or without split-thickness skin grafts, depending on the severity and extent of their burns.
Dermagraft (Advanced Biohealing, Westport, CT) is a polyglactin mesh seeded with neonatal fibroblasts. The mesh is resorbed and replaced with the patient’s own tissue. It is used as both a temporary and permanent dressing to increase the successful take of meshed split-thickness skin grafts on excised burn wounds and for venous and pressure ulcers. Dermagraft is equivalent to allograft with respect to infection, healing time, time to closure, and graft take.11
Apligraf (Organogenesis, Canton, MA) is a bilayered skin equivalent. The lower “dermal” layer consists of type I bovine collagen and fibroblasts obtained from neonatal foreskin, while the upper “epidermal” layer is derived from keratinocytes. It has a shelf life of 5 days at room temperature. It is used for venous ulcers and diabetic foot ulcers as well as a temporary covering over meshed autografts in excised burn wounds.
Currently available bioprosthetic mesh materials are derived from decellularized mammalian tissues, either human (allogeneic) or animal (xenogeneic). Bioprosthetic mesh materials are processed to remove cells and other potentially immunogenic components while preserving the native extracellular matrix architecture. An ideal mesh possesses the characteristics shown in Table 7.3.12 Several bioprosthetic mesh materials are available. These materials are commonly used for complex torso reconstruction and breast reconstruction.
Small Intestinal Submucosa
Small intestinal submucosa (SIS or Surgisis; Cook Biotech, West Lafayette, IN) is created from the small intestine of pigs. The submucosa of the small intestine provides mechanical strength to the intestine and contains a biochemically rich and diverse extracellular matrix. First described as a vascular graft in 1989, SIS has been applied to over 20 applications in humans including multiple types of hernia repair, dural repair, bladder reconstruction, and stress urinary incontinence treatment.13
Human Acellular Dermal Matrix
There are several products classified as human acellular dermal matrix (HADM) including AlloDerm (LifeCell Corp, Branchburg, NJ), Allomax (Bard Davol, Murray Hill, NJ), and FlexHD (Ethicon360, Somerville, NJ). Each manufacturer uses a proprietary technique to produce the HADM from donated allograft human dermis. In general, after the epidermis and subcutaneous tissue are removed, the dermis is processed, either with freeze-drying or chemical detergents, to eliminate everything but the collagen structure of the dermal matrix. Applications of HADM include implant-based breast, abdominal wall, chest wall, pelvis reconstruction, and lip augmentation.14,15 Micronized HADM (Cymetra; LifeCell, Branchburg, NJ) is also available and has been used for laryngoplasty and as soft-tissue filler.
Porcine Acellular Dermal Matrix
Porcine acellular dermal matrix (PADM) has been developed for applications similar to HADM. To inhibit immunogenicity and reduce collagenase-dependent matrix degradation, first-generation PADMs (CollaMend; Bard Davol, Cranston, RI and Permacol; Covidien, Norwalk, CT) undergo chemical cross-linking of the collagen fibers during the manufacturing process, which changes the extracellular matrix structure and inhibits cellular infiltration, revascularization, and matrix remodeling potential.
A newer generation of PADMs (Strattice; LifeCell Corp, Branchburg, NJ) is processed without chemical cross-linking. The [galactose-α (1,3)-galactose] antigen, which is the major cause of the immune response associated with acellular xenografts, is enzymatically removed.
It is not entirely clear which of these products has a better outcome. In a recent in vivo animal study comparing cross-linked PADM with non–cross-linked PADM for abdominal wall reconstruction, non–cross-linked PADM appeared to have early clinical advantages.16 No comparative human studies, however, have been preformed to date.
Other Bioprosthetic Mesh Products
Bovine pericardium (Veritas; Synovis, St. Paul, MN) is a non–cross-linked collagen matrix. Decellularization and reduction of immunogenicity is achieved by capping free amine groups using a proprietary chemical process.
Bovine fetal dermis (SurgiMend; TEI, Boston, MA) is an acellular matrix derived from fetal calves. It is not cross-linked and can facilitate cell penetration, revascularization, and integration with host tissues.
Biomaterials and implants have made huge impacts in medicine and surgery. Some implants are designed to have little interaction with the body. Others are designed to interact with the body in a passive way (e.g., biodegradable PLGA polymers). Recent biomaterials are being designed to modulate their environment to create a tissue-specific response. Furthermore, hybrid biomaterials containing cells, polymers, growth factors, etc. are currently being developed in in vivo models. These biomaterials will eventually “sense” their surroundings and change their biochemical/mechanical properties in response to the needs of the environment. The ultimate goal is the creation of biomaterials with tissue-specific properties individualized to the exact biologic, chemical, and functional needs of the reconstruction. The continued evolution of the biomaterial field depends upon an interdisciplinary collaboration between engineers, scientists, clinicians, and industry.
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