Lecture 8:

Bioceramic Materials:

Introduction

Bioceramic materials have developed into a very powerful driver of advanced

ceramics research and development. For many years bioceramics, both bioinert

materials such as alumina, zirconia and, to a limited extent titania and

bioconductive materials such as hydroxyapatite, tricalcium phosphate and calcium

phosphate cements, have been used successfully in clinical practice. In addition,

applications continue to emerge that use biomaterials for medical devices. An

excellent account of the wide range of bioceramics , in which issues of the

significance of the structure, mechanical properties and biological interaction of

biomaterials are discussed, and their clinical applications in joint replacement,

bone grafts, tissue engineering, and dentistry are reviewed.

Basic Aspects of Biomineralization

Human bone is a strong, tough, and highly durable composite material which

consists of about 70% micro - to nanocrystalline biological apatite and 30% micro

fibrils of collagen I, all of which are organized in a hierarchical manner, as shown

in Figure 10.1 anocrystals of bioapatite that are about 30 × 50 × 2 nm3 in size (G

and H in Figure 10.1) are arranged with their c – axes parallel to the extension of fi

ve collagen molecules which themselves consist of triple helical strands of

collagen fibers to form a microfibril (F). These inorganic – organic composite

microfi brils are bundled together to form larger fibrils (E) that are, in turn,

grouped to form even larger mineralized fi bers (D). Hence, a spatially hierarchical

organization exists that forms the basic structural units of bone. During the

formation of bone, the collagen I matrix develops first; this is followed by a second

step in which the hydroxyapatite nanocrystals become embedded.

The Concept and Definition of Biocompatibility

Any material that is incorporated into a human organism must abide by certain

properties, so as to ensure that there are no negative interactions with living tissues.

Biomaterials, by definition, are inorganic compounds that are designed to replace a

part or a function of the human body in a safe, reliable, economic, and

physiologically and esthetically acceptable manner as biomaterials are inorganic

structures, they do not include renewable “ biological ” materials obtained from

natural sources such as wood, plant fibers, hides, sinew, bone, ivory, and others.

In increasing order of biocompatibility the interaction of biomaterials with living

tissue can be defined as follows:

• Incompatible materials release to the body substances in toxic concentrations,

and/or they trigger the formation of antigens that may cause immune reactions.

Such reactions may range from simple allergies, to inflammation, to septic

rejection, with the associated severe health consequences.

• Biocompatible materials also release substances, albeit in nontoxic

concentrations, that may lead only to benign tissue reactions such as the formation

of a fibrous connective tissue capsule, or weak immune reactions that cause the

formation of giant cells or phagocytes.

• Bioinert materials do not release any toxic constituents, but neither do they show

any positive interactions with living tissue. The body generally responds to these

materials by forming a nonadherent capsule of connective tissue around the

bioinert material. In the case of bone remodeling, this manifests itself by a shape -

mediated contact osteogenesis . Only compressive forces can be transmitted

through the bone – material interface ( “ bony on - growth ” ). Typical bioinert

materials include titanium and its alloys, ceramics such as alumina, zirconia and

titania, and some polymers, as well as carbon (see Table 10.1 ).

• Bioactive materials show a positive interaction with living tissues that includes

also the differentiation of immature cells towards bone cells. In contrast to bioinert

materials, a chemical bonding to the bone occurs along the interface; this is

thought to be triggered by the adsorption of bone growth – mediating proteins at

the biomaterials surface. Hence, there will be a biochemically mediated, strong

bonding osteogenesis . In addition to compressive forces, to some degree tensile

and shear forces can also be transmitted through the interface ( “ bony in - growth

” ). Typical bioactive materials include calcium phosphates and bioglasses (see

Table 10.1 ). It is believed that the bioactivity of calcium phosphates is associated

with the formation of hydroxycarbonate apatite ( HCA ), similar to bone - like

apatite.

Mechanical Properties of Advanced Bioceramics: Alumina versus Zirconia

As noted in detail above, it is mandatory that any material introduced into the

human body with the intent to remain there during the long term must be tolerated

by the organism. In particular, biocompatibility must be achieved, as defined

above. On the other hand, there are extremely strong quantitative differences of the

mechanical properties and responses to external loads between natural bone and

bioinert ceramics, as shown in Table 10.2 . These differences lead to strong

gradients of the modulus of elasticity (Young ’ s modulus) that give rise to so –

called “ stress shielding ” ; this means that the load placed on the implant during

movement will not be transmitted by the bone but rather through the stiff ceramic

femoral ball into the likewise very stiff titanium alloy stem. Since regular tensile

loads are required for living bone to stay healthy, an absence of loads will

eventually lead to the atrophic loss of cortical bone matter.

Whilst alumina is stiffer and has a higher compressive strength than Y – TZP, the

latter performs better mechanically, in terms of tensile and flexural strengths and,

in particular, fracture toughness. This is related to a delay of the well - known

martensitic phase transformation from the tetragonal high - temperature to the

monoclinic low - temperature modification of zirconia by stabilization with other

oxides, most often yttria, but also calcia and magnesia. The resultant so - called “

transformation toughening ” accounts for the dissipation of crack energy by a

delayed transformation of metastable tetragonal grains to thermodynamically

stable monoclinic grains with a lower density.

Hence, transformation to a phase with a lower density will exert compressive

stresses onto the surrounding ceramic matrix that slows down and eventually

arrests any crack movement; for a ceramic material this would lead to

exceptionally high fracture toughness values. It should be noted, however, that the

fracture toughness of cortical bone exceeds even that of stabilized zirconia, thus

confirming Nature ’ s impressive ingenuity to design strong and tough, but

lightweight, structures.

Previously, attempts have been made to reduce the stiffness differences between

the implant and bone by using “ isoelastic ” implants. In this case, a sheath of

polymer surrounds the metallic shaft of a hip endoprosthetic implant, the aim being

to provide a smooth gradient of the modulus of elasticity. Unfortunately, however,

degradation of the polymer within the harsh body environment has hampered this

approach so far.

Selected Bioceramic Materials

1 Bioinert Ceramics

1-1 Alumina

Extremely pure, fine - grained alumina polycrystals have been used for about 35

years for the femoral heads of hip endoprostheses. Today, there exists a large

variety of clinical options to combine femoral heads and acetabular cups. In

Germany, these medical products are marketed under the brandname BIOLOX ®

and BIOLOX ®. In 2000, the German market volume of ceramic femoral heads

amounted to about DM 30 million; this corresponded to 90 000 units, 90% of

which were made from alumina.

Novel developments in the field of femoral heads for hip endoprostheses rely on

high - purity alumina with the addition of 17 vol% tetragonally stabilized zirconia

and 1.4 vol% chromia particles (BIOLOX ® delta). The former provides

mechanical strengthening by transformation toughening, while the latter acts as a

reinforcement, dissipating the crack energy by deflecting the crack paths. The use

of these mechanisms leads to an almost threefold increase in the four - point

bending strength (to 1400 MPa) when compared to unalloyed alumina (Table

10.3 ), while the fracture toughness is increased to 6.5 MN · m− 3/2 . This latest

trend in load - bearing materials for arthroplastic applications involves the

development of highly fracture - resistant alumina/zirconia composites, as an

alternative choice to alumina and zirconia monolithic ceramics. Composite

materials are designed from both chemical and microstructural viewpoints in order

to prevent environmental degradation and fracture events in vivo . Based on the

experimental determination of an activation energy value for an environmentally

driven tetragonal to monoclinic transformation, the long - term in vivo

environmental resistance of prostheses made from these composite materials can

be predicted.

The properties and required purity of the alumina used in biomedical applications

are summarized in Table 10.3. The new ISO 6474/2 norm (established in 1994)

deviates from the former in that a much lower average grain size is specified, with

a concurrent increase in the flexural strength to beyond 450 MPa. This can be

achieved by grain boundary engineering during which the suppression of grain

growth at high sintering temperatures is achieved by the addition of small amounts

of magnesium oxide. The accumulation of magnesium oxide along the grain

boundaries of alumina will result in a thin surface layer consisting of spinel

(MgAl2O4), which acts as a barrier towards the grain boundary movement

associated with the process of recrystallization. Hence, the formation of large

grains by recrystallization will be effectively suppressed.

1-2 Y - Stabilized Zirconia (Y-TZP)

Zirconia materials – and in particular tetragonal zirconia partially stabilized with

yttria (Y-PSZ), magnesia (Mg-PSZ) and calcia (Ca-PSZ) – have found various

applications in biomedical devices, the most important being as hard and tough

structural ceramic materials for femoral balls in hip endoprostheses and as

materials for restorative dentistry. Since stabilized zirconia shows a substantially

larger fracture toughness ( KIc ) compared to alumina, it might be applied

advantageously in prosthetic devices. The routes of synthesis and the general

mechanical, chemical, and tribological properties of zirconia, as well as the

principles of the toughening mechanism by suppressing the tetragonal - to –

monoclinic phase transition.

Since zirconia is produced from naturally occurring zirconium silicate (zircon,

ZrSiO4) or baddeleyite (monoclinic m-ZrO2), trace amounts of uranium and

thorium (replacing the isovalent zirconium ion in the crystal lattice) may remain in

the processed material, rendering it slightly radioactive. Some selected properties

of commercially available Y - TZP are listed in Table 10.4.

2- Bioconductive Ceramics

2-1 Bioglasses

Since the discovery during the late 1960s of surface - active bioglasses that bond to

living tissues, various types of bioactive glass and glass - ceramics have been

developed with different functions, including high mechanical strength, high

machinability, and fast setting ability. The glasses investigated for implantation are

based primarily on silica (SiO2), but containing small amounts of other crystalline

phases. The most prominent and successful application of this is Bioglass, which

was developed almost single – handedly. Bioactive glass compositions are

positioned in the system CaO–Na2O–P2O5–SiO2. The first development of such a

bioglass composition began during the 1970s, when 45S5 Bioglass ® was

proposed with a composition of 45% SiO2, 24.5% CaO, 24.5% NaO2 , and 6% P2O5

by weight. Subsequently, suggested that bioglass ® 45S5 had a greater osteoblastic

activity than HAp. One common feature of bioactive glasses is a time - dependent

kinetic modification of their surfaces during implantation. While they are generally

nonresorbable, the release of sodium and calcium ions triggers a cascade of

reactions culminating in the nucleation of a thin layer of biological

hydroxycarbonate apatite ( HCA ) that provides a bonding interface with bony

tissues. This interface is so mechanically strong that, in many cases, the interfacial

strength of the adhesion exceeds the cohesive strength of the implant material, or

of the tissue to which it is bonded.

Application of Bioactive Glasses As the technology of bioactive glasses for

medical use is relatively new, only a relatively few – but highly successful –

clinical applications of these materials have been made. Perhaps most important

point here is the absence of any reports of adverse responses to these materials in

the body, thus confirming the antibacterial and antifungal properties of bioglasses.

Today, the most typical applications of bioglasses include:

• Dental implants

• Periodontal pocket obliteration

• Alveolar ridge augmentation

• Maxillofacial reconstruction

• Otolaryngologic applications

• Percutaneous access devices

• Spinal fusion

• Coatings for dialysis catheters made from silicone tubing

• Coatings for surgical screws and wires

• Cochlear implants

• Bone graft substitutes

• Bone tissue engineering scaffolds

• Antibacterial and antifungal applications as wound - healing agents

• Granular filler for jaw defects following tooth extraction.

2-2 Hydroxyapatite

Hydroxyapatite is chemically and structurally very close to naturally occurring

biological apatite which forms the inorganic scaffolding materials of bone.

Unfortunately, however, as a synthetic ceramic material it is mechanically quite

weak, and hence is unable to sustain even moderate tensile, shear or compressive

forces. Consequently, HAp cannot be applied as a monolithic material but rather in

either granular form to fill larger bone cavities, as coatings for metallic implants, or

as a composite material together with biodegradable polymers such as collagen,

poly(lactic acid) ( PLA ), poly(caprolactone) ( PCL ), poly(etheretherketone)

( PEEK ), or polyamides (Nylon ® 6/12).

2-3 Calcium – Titanium – Zirconium Phosphates

Calcium – titanium – zirconium phosphate ceramics show solubilities in SBFs that

are at least one order of magnitude lower than those of HAp and, in particular, than

of TCP. The plasma - spraying of coatings of this composition result in a good

adhesion to Ti6Al4V substrates (>40MPa), even though considerable thermal

decomposition has been observed to form zirconium pyrophosphate (ZrP2O7 ),

rutile (TiO2), and baddeleyite (β-ZrO2). There is some evidence, however, that

these bioinert products of incongruent melting of the coating material may lead to a

particle - mediated reinforcement of the coating microstructure . In vitro

biocompatibility tests with primary rat bone marrow cells have demonstrated

substantial cell proliferation in the presence of fetal bovine serum. Subsequent

studies conducted in sheep indicated that 150 μm - thick coatings based on

CaTiZr3(PO4)6 , when applied to Ti6Al4V rods implanted in the femur, led to a

strong neoformation of dense bone at a stable implant – bioceramic interface

coating, but without the coating delamination often observed with HAp. The build

- up of a Ti6Al4V/TiO2/NASICON/(HAp) coating system could lead to a “ bio ” -

capacitor which, by correct poling, could be used to store negative electrical

charges close to the interface with the growing bone, thus enhancing the bone

apposition rate and, presumably.