AAOS Comprehensive Orthopaedic Review

Section 1 - Basic Science

Chapter 3. Biomaterials

I. General Information

A. Biomaterials are synthetic or naturally derived materials that are used in vivo to replace or augment function.

 

B. Uses—Biomaterials are used for internal fixation of fractures, osteotomies and arthrodeses, wound closure, tissue substitution, and total joint arthroplasty.

 

C. Orthopaedic requirements—Orthopaedic biomaterials must be biocompatible (able to function in vivo without eliciting detrimental local or systemic responses), resistant to corrosion and degradation (able to withstand the in vivo environment), and have adequate mechanical and wear properties.



II. Biocompatibility

A. Inert—Little or no host response.

 

B. Interactive—Designed to elicit specific beneficial responses such as tissue ingrowth (porous tantalum).

 

C. Viable—Incorporates and attracts cells that are then resorbed and remodeled (biodegradable polymeric scaffolds for functional tissue engineering).

 

D. Replant—Native tissue that has been cultured in vitro from cells obtained from a specific patient (chondroplasty).

 

E. Not biocompatible—Elicits unacceptable biologic reactions.



III. Corrosion and Degradation Resistance

A. The in vivo environment of the human body can be highly corrosive.

 

B. Corrosion can weaken implants and release products that can adversely affect biocompatibility and cause pain, swelling, and destruction of nearby tissue.

 

C. Orthopaedic devices can be susceptible to several modes of corrosion.

 

1. Galvanic corrosion is the result of the electro-chemical potential created between two metals in a conductive medium such as serum or interstitial fluid.

 

a. Galvanic corrosion is seen in fracture fixation plates at the interface between the plate and the screws or constructs when different metals are used.

 

b. It is best avoided by minimizing impurities that can enter the material during manufacturing and by ensuring consistent preparation of implant materials.

 

2. Fretting corrosion results at contact sites between materials that are subject to relative micromotion when under load.

 

a. Fretting corrosion is seen in modular arthroplasty devices that make use of tapered junctions.

 

b. It is best prevented by avoiding implant junctions and/or micromotion.

 

3. Crevice corrosion results from differences in oxygen tension within and outside of a crevice with an associated differential in electrolytes and pH

 

a. Crevice corrosion is seen at holes in devices such as plates and uncemented acetabular components.

 

b. It is best avoided by minimizing surface defects that might be created during manufacturing and intraoperative handling.

 

4. Pitting corrosion is a form of localized, symmetric corrosion in which pits form on the metal surface.

 

5. Degradation of orthopedic biomaterials such as polymers

 

a. This is a form of corrosion resulting from exposure to harsh environments.

 

b. Most common: oxidating degradation of ultra-high-molecular-weight polyethylene (UHMWPE) components for total joint arthroplasty.

 

[

Figure 1. Stress and deformation in a material subjected to axial tensile force. F = force; A = area; L = length; ΔL = change in length.]

[

Figure 2. The stress-strain curve can be divided into two distinct deformation regions, elastic and plastic. The yield stress defines the transition point from elastic to plastic deformation, where a material is no longer able to recover to its preloading condition. The slope of the stress-strain curve in the elastic deformation region is the modulus of elasticity.]

IV. Mechanical Properties

A. Performance factors—The mechanical performance of an orthopaedic device depends on several factors:

 

1. The forces to which it is subjected

 

2. The mechanical burdens of those forces

 

3. The ability of the materials to withstand those burdens over the device lifetime

 

B. Definitions

 

1. Load—The force that acts on a body.

 

a. Compression/tension—Forces perpendicular to the surface of application.

 

b. Shear—Forces parallel to the surface of application.

 

c. Torsion—Force that causes rotation.

 

2. Stress—intensity of a force over a cross section

 

a. Stress (E) = force (F)/cross-sectional area (A) (Figure 1).

 

b. The SI unit for stress is newtons/meter2 (N/m2) or Pascals (Pa).

 

c. A force that acts perpendicularly to a surface results in a normal stress.

 

d. A force that acts tangentially to a surface results in a shear stress.

 

e. A stress is tensile if the material is stretched by the force and compressive if the material is compressed by the force.

 

[

Table 1. Orthopaedic Materials in Order of Modulus of Elasticity (E)]

3. Strain—Deformation of the material due to a force application.

 

a. Strain (σ) = change in length (ΔL)/original length (L).

 

b. The types of strain associated with normal and shear stress are called normal strain and shear strain, respectively.

 

c. Like stress, strain can be either tensile or compressive.

 

4. Stress-strain curve

 

a. A typical stress-strain diagram for a material is shown in Figure 2.

 

b. The stress-strain ratio, or modulus of elasticity (E), is the slope of a stress-strain curve. This is unique to each material. The modulus of elasticity is a measure of an object's ability to resist deformation under the application of an external load (Table 1).

 

c. A higher modulus of elasticity indicates a material that is stiffer and more resistant to deformation.

 

d. As the stress increases, the slope of the stress-strain curve changes when it reaches the point called yield stress. Up to this point, the material has been in its elastic area, which means that if the specimen unloads gradually, the strain decreases until the material reaches its original shape.

 

e. The yield stress is the transition point between elastic and plastic deformation. When the stress reaches the yield point, yielding occurs

 

[

Figure 3. Typical stress-strain curves for brittle materials (red) and ductile materials (blue). Brittle materials demonstrate little plastic deformation, and they fail at a relatively low strain. Ductile materials undergo large strains during plastic deformation before failure.]

   and the material starts demonstrating plastic behavior. Beyond the yield point, the stress either does not increase or it increases only slightly, but considerable elongation occurs.

 

f. The maximum stress a material can support is called the ultimate stress. Beyond the ultimate stress, the stress decreases while the material elongates, until fracture or failure occurs.

 

g. A material can be classified as either brittle or ductile, based on the characteristics of the stress-strain curve.

 

i. A brittle material exhibits very little plastic deformation before fracture, and it fails in tension at relatively low strain (Figure 3). Examples of brittle materials are concrete, stone, cast iron, glass, ceramic materials, and many common metallic alloys.

 

ii. In contrast, ductile materials undergo large strains during plastic deformation before failure. Mild steel, aluminum, copper, magnesium, lead, nickel, brass, bronze, nylon, and Teflon are examples of ductile materials.

 

h. Toughness is represented by the area under the stress-strain curve; it is an indication of the amount of energy the material can withstand before rupture.

 

i. Fatigue failure is failure related to cyclic loading.

 

i. This is the most common mode of failure in orthopaedic applications.

 

ii. When a material is subjected to a dynamic load with a large number of loading cycles, failure will occur at a lower stress than the ultimate stress of static loading. The stress at failure decreases as the number of cycles increases.

 

[

Figure 4. Biologic materials demonstrate viscoelastic properties. Because of the uncrimping of collagen fibers and the elasticity of elastin, the initial portion of a stress-strain curve for a biologic sample has a high deformation/low force characteristic known as the toe region. In the linear region, slippage initially occurs within collagen fibrils, then between collagen fibrils; finally, tearing of the fibrils and tissue failure occurs. From this curve, the stiffness (slope of the curve), the ultimate load (load at failure), and the energy absorbed to failure (toughness, area under the curve) can be calculated.]

iii. Fatigue failure consists of three steps: the initiation of a crack, the propagation of the crack, and catastrophic failure.

 

iv. The endurance limit (fatigue strength) is the stress at which the material can withstand 10 million stress cycles.

 

j. Isotropic materials have the same mechanical properties in all directions (eg, stainless steel, titanium alloys).

 

k. Anisotropic materials exhibit varying mechanical properties with different directions of loading (eg, bone, cartilage, muscle, ligament). This anisotropic behavior is a result of specifically oriented consitutent parts such as collagen fibrils and/or hydroxyapatite (HA) crystals.

 

l. Viscoelastic materials exhibit stress-strain curve patterns that are time/rate dependent as a result of the internal friction of a material (eg, ligaments, tendons) (Figure 4).

 

i. The modulus of elasticity of a viscoelastic material increases as the strain rate increases.

 

ii. Hysteresis is the area between the load and unload portions of a stress-strain curve.

 

iii. Creep is increased displacement of a material over time due to a constant force.

 

iv. Stress relaxation is a decrease in stress over time due to a constant displacement.

 

v. Polar moment of inertia is the quantity that is determined by the cross-sectional area and distribution of tissue around a neutral axis in torsional loading. The larger the polar moment of inertia, the stiffer and stronger the material.



V. Biomechanical Properties of Specific Compounds

A. Host tissue

 

1. Bone

 

a. Bone is a composite of inorganic mineral salts (mainly calcium and phosphate) and organic matrix (mainly type I collagen and ground substance). The inorganic component makes bone hard and rigid, whereas the organic component gives bone its flexibility.

 

b. Bone is anisotropic as a result of the orientation of its components.

 

c. Bone is stiffer and stronger and stores more energy when loaded at higher rates (viscoelastic).

 

d. Macroscopically, skeletal tissue is composed of cortical and cancellous (trabecular) bone. Bone of both types can be considered as one material with widely varying porosity and density.

 

e. The apparent density of bone is determined by the mass of bone tissue divided by the volume of the specimen.

 

i. The apparent density of cortical bone is approximately 1.8 g/cm3.

 

ii. The apparent density of trabecular bone ranges from 0.1 g/cm3 to 1.0 g/cm3.

 

f. With aging, a progressive net loss of bone mass occurs beginning in the fifth decade and proceeding at a faster rate in women. This results in reduced bone strength, a reduced modulus of elasticity, and increased likelihood of fractures.

 

g. Several radiographic studies have suggested that aging is associated with bone remodeling that affects force distribution.

 

i. Subperiosteal apposition of bone occurs along with endosteal absorption in tubular bones, creating a cylinder of larger diameter.

 

ii. This remodeling of the diaphysis is hypothesized to serve as a mechanical "compensatory" function by increasing the moment of inertia as the cortex thins with aging. Essentially, the effective bone is shifted to a more peripheral location.

 

iii. The increase in outer diameter from bone apposition is much smaller in women than in men, potentially predisposing women to an increased rate of fracture.

 

2. Tendons

 

a. Tendons consist predominantly of type I collagen.

 

b. Tendons transmit muscle forces to bone.

 

i. Tendons center the action of several muscles into a single line of pull (eg, Achilles tendon)

 

ii. They distribute the contractile force of one muscle to several bones (eg, posterior tibialis).

 

iii. Tendons allow the direction of pull to be changed in conjunction with a pulley (eg, posterior tibialis tendon around the medial malleolus).

 

c. Tendons are anisotropic as a result of the orientation of their components.

 

d. Tendons are viscoelastic.

 

i. Under low loading conditions, tendons are relatively compliant.

 

ii. With increasing loads, tendons become increasingly stiff until they reach a range where they exhibit nearly linear stiffness.

 

e. Many tendons are composed of portions of varying orientation that may experience variable loads with any action. Loads applied obliquely during eccentric contractions pose the highest risk of tendon ruptures.

 

f. The ultimate load of the tendon usually is greater than that of the muscle or its insertion; thus, muscle ruptures or tendon avulsions are more common than ruptures of the tendon itself. Midsubstance disruptions of a tendon usually occur only in a tendon with pre-existing disease before tensile overload (eg, Achilles tendon with tendinosis).

 

3. Ligaments

 

a. Ligaments are composed predominantly of type I collagen.

 

b. Ligaments connect bones to bones.

 

i. The bony attachment of ligaments is very important to their structural strength.

 

ii. Forces directed perpendicular to the insertions have been shown to cause shear failure of the ligament at the bony interface at relatively low loads.

 

c. Similar to tendons, ligaments are viscoelastic, with properties dependent on the rate of load application.

 

[

Table 2. Metals Used in Orthopaedic Applications]

B. Metals

 

1. Metals are crystalline arrays. Within each crystal, the atoms are regularly spaced and packed in specific configurations, allowing for the sharing of outer electrons that give rise to excellent heat and electrical conductivity.

 

2. Alloys are mixtures of metals or of metals and nonmetallic elements.

 

3. Metals are typically fabricated by casting, forging, or extrusion.

 

a. Casting—Molten metal is poured into a mold.

 

b. Forging—One half of a die is attached to a hammer and held and heated metal is worked with an anvil.

 

c. Extrusion—Metal is heated and forced through a hole to obtain a long piece with a uniform cross section.

 

4. Several alloys are commonly used in orthopaedics (Table 2).

 

a. Stainless steel (most common alloy is 316L)

 

i. The ductility of stainless steel is important in applications such as bone screws where a definite yield point allows the surgeon to feel the onset of plastic deformation.

 

ii. Carbon is added to form metallic carbides that impart strength to the material. If carbide concentrations are too high, however, carbides segregate at the grain boundaries, significantly weakening the steel by making it prone to corrosion-related fracture.

 

iii. Stainless steel is susceptible to galvanic and crevice corrosion, although corrosion resistance can be improved by increasing chromium, molybdenum, and nitrogen concentrations.

 

b. Cobalt alloys

 

i. The predominant fabrication technique is casting.

 

ii. Cobalt alloys are among the strongest orthopaedic implant materials and are suitable for high-load applications that require longevity.

 

c. Titanium and its alloys

 

i. Pure titanium is typically used for fracture fixation where large loads are not expected (eg, maxillofacial, wrist, phalanges). Pure titanium is less ductile than stainless steel, however, and increased incidence of screw breakage is often noted.

 

ii. For higher-strength applications, titanium alloys must be used (eg, titanium-aluminum-vanadium, Ti-6Al-4V, which has a high strength-to-weight ratio).

 

d. Tantalum

 

i. A transitional metal that is highly corrosion resistant

 

ii. Facilitates bony ingrowth

 

C. Polymers

 

1. Polymers are large molecules made from combinations of smaller molecules. The properties of a polymer are dictated by

 

a. Its chemical structure (the monomer)

 

b. The molecular weight (the number of monomers)

 

c. The physical structure (the way monomers are attached to each other)

 

d. Isomerism (the different orientation of atoms in some polymers)

 

e. Crystallinity (the packing of polymer chains into ordered atomic arrays)

 

2. Polymethylmethacrylate (PMMA) is the most commonly used polymer in orthopaedics.

 

a. PMMA is produced from two components, a liquid and a powder.

 

i. The liquid component is predominantly a methylmethacrylate monomer and does not polymerize until it comes into contact with the initiator.

 

ii. The powder is composed mainly of a polymerized PMMA or a blend of PMMA with a copolymer of both PMMA and polystyrene or PMMA and methacrylic acid. The powder also contains the initiator, dibenzoyl peroxide.

 

iii. Mixing the two components results in an exothermic reaction.

 

b. Antibiotics can be added to PMMA bone cement to provide prophylaxis or aid in the treatment of infection. Adding antibiotics during the mixing process, however, can negatively affect the properties of PMMA bone cement by interfering with the crystallinity of the polymer.

 

c. The performance of PMMA cement has been enhanced by improved protocols in handling, bone preparation, and cement delivery.

 

d. Vacuum mixing or centrifugation of the cement may decrease the porosity of PMMA cement, increasing ultimate tensile strength by ~ 40%.

 

3. UHMWPE is another polymer commonly used in orthopaedics.

 

a. This long polyethylene polymer has a very high molecular weight, imparting significantly higher impact strength, toughness, and better abrasive wear characteristics than polyethylenes of lesser weights.

 

b. Three methods are used to fabricate orthopaedic components from UHMWPE.

 

i. Ram extrusion—The resin is extruded through a die under heat and pressure to form a cylindrical bar that in turn is machined into the final shape.

 

ii. Compression molding—The resin is modeled into a large sheet that is cut into smaller pieces to use in machining the final components.

 

iii. Direct molding—The resin is directly molded into the finished part.

 

c. The most common method for sterilizing UHMWPE components is by exposure to gamma radiation.

 

d. Postirradiation oxidation adversely affects the material properties of UHMWPE by increasing the modulus of elasticity, decreasing the elongation to break, and decreasing the toughness. Free radicals generated from radiation may follow one of several paths:

 

i. Recombination—The bonds that were broken are simply re-formed; no net change in chemistry.

 

ii. Chain scission—Free radicals may react with oxygen, fragmenting the polymer chain. The resulting polyethylene will have a lower molecular weight and increased density.

 

iii. Cross-linking—Free radicals from different polymer sections combine to form chemical bonds between two polymer chains. A cross-linked polymer may be harder and more abrasion resistant. Extremely high levels of cross-links may result in the material becoming increasingly brittle. Increased cross-linking with either gamma or electron beam irradiation improves wear resistance in polyethylene components used in total joint arthroplasty. However, the process has a negative effect on fracture and fatigue properties.

 

iv. Degradation is a breakdown of the polymer chain. This may be avoided or minimized in two ways.

 

(a) Sterilization methods that do not involve irradiation, such as ethylene oxide or gas plasma, do not generate free radicals and therefore do not create any cross-linking. However, recent clinical studies of total hip arthroplasty patients have demonstrated significantly less wear with radiation sterilization than with sterilization using ethylene oxide or gas plasma.

 

(b) Irradiation in the absence of oxygen with nitrogen or argon minimizes free radical formation.

 

4. Biodegradable polymers that degrade chemically and/or physically in a controlled manner over time can be synthesized.

 

a. Examples include variations of polylactic acid (PLA), polyglycolic acid (PGA), polydioxanone, and polycaprolactone. PLA has been a desirable choice because its degradation product is lactic acid, a natural constituent of the Krebs cycle.

 

b. These polymers are resorbed at different rates.

 

i. PLA resorbs faster than PGA.

 

ii. Composite products may have intermediate properties.

 

c. Resorption allows the host tissue to assume its normal role as the load-sharing capabilities of the polymer decrease. This must be balanced with the need for maintaining mechanical properties.

 

d. Resorbable polymers can also be used in drug delivery, releasing the drug as the polymer degrades.

 

5. Hydrogels—Networks of polymer chains that have been considered for use in a wide range of applications, including tissue engineering.

 

a. These materials are soft, porous, permeable polymers that absorb water readily.

 

b. Hydrogels have low coefficients of friction and time-dependent mechanical properties that can be varied through altering the material's composition and structure.

 

D. Ceramics

 

1. Ceramics are solid, inorganic compounds consisting of metallic and nonmetallic elements held together by ionic or covalent bonds.

 

2. Ceramics include compounds such as silica (SiO2) and alumina (Al2O3).

 

3. Ceramics are typically three-dimensional arrays of positively charged metal ions and negatively charged nonmetal ions such as oxygen.

 

4. When processed to high purity, ceramics possess excellent biocompatibility because of their insolubility and chemical inertness.

 

5. Ceramic materials are very stiff and brittle but are very strong under compressive loads.

 

6. Ceramics have gained favor for two different orthopaedic applications: total joint arthroplasty (TJA) components and bone graft substitutes.

 

a. Bearings—ceramic-on-polyethylene and ceramic-on-ceramic bearings are becoming more widely used in TJA.

 

i. Ceramics have high hardness and a high modulus of elasticity, allowing them to be polished to a very smooth finish and to resist roughening while in use as a bearing surface.

 

ii. Ceramics also have good wettability, suggesting the possibility of forming lubricating layers between ceramic couplings to reduce adhesive forms of wear.

 

iii. Alumina, in the form of aluminum oxide, has shown lower wear rates than conventional metal-on-polyethylene bearings. Although early clinical experience showed fracture of alumina femoral heads to be a significant complication, this problem appears to be design related, and newer-generation designs have shown significantly lower fracture rates.

 

iv. Zirconia, in the form of zirconia oxide, has shown less clinical success than alumina when used as a bearing surface against polyethylene. Zirconia oxide has lower toughness, which makes the material more susceptible to roughening and increased wear.

 

b. Bone substitutes

 

i. Certain ceramics have been found to be osteoconductive in nature and have accordingly been developed as bone graft materials.

 

ii. Hydroxyapatite (HA)

 

(a) HA is a hydrated calcium phosphate that is similar in crystalline structure to the mineral of bone.

 

(b) Its structural and inorganic components differ from those of bone.

 

(c) HA is very slow to resorb.

 

iii. β-tricalcium phosphate (β-TCP) and calcium sulfate are other alternatives. These materials have less strength and faster resorption than HA products.

 

iv. Other molecules, such as silicone (Si), have been shown to induce bone formation when combined with other ceramics.



Top Testing Facts

1. Stress—Force per unit area.

 

2. Strain energy is the amount of energy stored in a loaded material. In a stress-strain curve, it represents the area under the curve.

 

3. Modulus of elasticity is the ratio of stress to strain; it measures the ability of a material to maintain its shape under the application of external load. The higher the modulus of elasticity, the stiffer the material.

 

4. Polar moment of inertia is the quantity that is determined by the cross-sectional area and distribution of tissue around a neutral axis in torsional loading. The larger the polar moment of inertia, the stiffer and stronger the material.

 

5. A viscoelastic material has properties that are rate dependent or have time-dependent responses to applied forces.

 

6. An isotropic material has the same mechanical properties in all directions. In general, ceramics and metals are isotropic.

 

7. An anisotropic material has properties that differ depending on the direction of load. Bone, muscle, ligament, and tendon all are anisotropic.

 

8. Alloys are metals composed of mixtures or solutions of metallic and nonmetallic elements that are varied to influence their biomechanical properties, including strength, stiffness, corrosion resistance, and ductility.

 

9. The properties of a polymer are dictated by its chemical structure (the monomer), the molecular weight (the number of monomers), the physical structure (the way monomers are attached to each other), isomerism (the different orientation of atoms in some polymers), and crystallinity (the packing of polymer chains into ordered atomic arrays).

 

10. Ceramics are solid, inorganic compounds consisting of metallic and nonmetallic elements held together by ionic or covalent bonds.



Bibliography

Behravesh E, Yasko AW, Engel PS, Mikos AG: Synthetic biodegradable polymers for orthopedic applications. Clin Orthop Relat Res 1999;367:S118-S129.

Einhorn TA, O'Keefe RJ, Buckwalter JA (eds): Orthopaedic Basic Science: Foundations of Clinical Practice, ed 3. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2007.

Hamadouche M, Sedel L: Ceramics in orthopaedics. J Bone Joint Surg Br 2000;82:1095-1099.

Jacobs JJ, Gilbert JL, Urban RM: Corrosion of metal orthopedic implants. J Bone Joint Surg Am 1998;80:268-282.

Lewis G: Properties of acrylic bone cement: State of the art review. J Biomed Mater Res 1997;38:155-182.

Li P: Bioactive ceramics: State of the art and future trends. Semin Arthroplasty 1998;9:165-175.

Morita M, Sasada T, Hayashi H, Tsukamoto Y: The corrosion fatigue properties of surgical implants in a living body. J Biomed Mater Res 1988;22:529-540.