ceramics biomaterials
DESCRIPTION
Ceramic BiomaterialsTRANSCRIPT
3. Ceramic biomaterials: contents 3.0 Ceramics
(1) Definition
(2) Characteristics
3.1 Outline of ceramic biomaterials
(1) Applications
(2) Classification
3.2 Ceramic biomaterials
(1) Oxides
(2) Glasses
(3) Calcium phosphates 1
3.0 Ceramics
(1) Definition
2
Definition
“Ceramics” from keramos (the Greek word)
the art and science of making and using solid
articles formed by the action of heat on earthy raw
materials
the art and science of making and using solid articles
which have as their essential component, and are
composed in large part of, inorganic materials
(Introduction to ceramics, 2nd edition, 1976)
Inorganic and nonmetallic solid materials
3
Ceramics
metal-nonmetal compounds: TiC, Al2O3, ZrN, ・・・ semi metal-nonmetal compounds: SiC, SiO2, BN, ・・・ crystalline, non-crystalline oxide, carbide, nitride, boride, ・ ・・ pottery, glass, refractory, cements, structural clay products , ・ ・・ + new ceramics (fine ceramics)
4
Fine ceramics
According to ISO 20507: Fine ceramics (advanced ceramics,
advanced technical ceramics) - Fine Ceramics are " highly
engineered, high performance, predominantly non-metallic,
inorganic, ceramic material having specific functional
attributes".
the 1980s: fine ceramics boom
(magnetic, ferroelectronic, structural,,,)
1986: High-temperature superconductor
(La-Ba-Cu-O system)
Improvement in processing and purity of ceramic source powders
development of bioceramics 5
3.0 Ceramics
(2) Characteristics
6
Characteristics of ceramics Chemical bonding: ionic and covalent bonding
high melting point
high hardness
high chemical stability
high elastic modulus
high creep property
low density
low thermal expansion coefficient
brittle(脆性)
poor workability(難加工性)
sensitive to flaw(欠陥に敏感)
Anisotropy in bonding direction
7
Mechanical properties of ceramics
(A. Nozue, Bull. Ceramic Soc. Jpn., 38 (2003), 21.)
Materials Tensile strength (MPa)
Bending strength (MPa)
Compressive strength (MPa)
Elastic modulus (GPa)
Fatigue limit (MPa)
Fracture toughness (MPa/m1/2)
Cortical bone
Cancellous bone
Ti-6Al-4V alloy
Co-Cr-Mo alloy
Titanium
Alumina
Zirconia
Hydroxyapatite
8
9
Stress-strain curves
Figure 1-1 Schematic illustration of stress-strain curves of biomaterials.
(中野貴由:医療用金属材料概論, (2010), 191)
Comparison with other biomaterials
Materials Examples Advantages Disadvantages
Metals
Titanium and its alloys
Co-Cr alloys
Stainless steels
Au, Ag, Pt
Excellent balance of strength
and ductility
Shape memory effect
Electrical conductivity
Thermal conductivity
May corrode
High density
Ceramics
Alumina(Al2O3)
Zirconia(ZrO2+oxide)
Hydroxyapatite
(Ca10(PO4)6(OH)2)
Calcium phosphate
Very biocompatible
High strength
High wear resistance
Inert
Brittle
Not resilient
Difficult to make
Polymer
Silicone
Polymethylmethacrylate
(PMMA)
Polyethylene
Easy to fabricate
Low density
Resilient
Not strong
Deforms with time
May degrade
Ceramics Wear resistance
Chemical stability
Biocompatibility with bone
Table 1-3 Classification of biomaterials by structure and chemical bond.
10
3.1 Outline of ceramic biomaterials
(1) Applications
11
Applications
Orthopedic (整形外科)
Dental (歯科)
Coating (コーティング材)
+
Scaffold (足場材料)
(Biomaterials Science, An Introduction to Materials in
Medicine 2nd Ed. Elsevier, (2004), p.162.) 12
Ceramic biomaterials
耐摩耗性 人工股関節骨頭 人工歯(上部構造) 生体活性 骨と化学的に結合する 人工骨(骨充填材) 生体吸収性 骨と置換する 人工骨(骨置換材) 再生医療用足場材料
Orthopedic field: materials used in Japan
Figure 2-1 Mass of biomaterials in orthopedic field in Japan. (T. Narushima, J. Jpn. Inst. Light Metals, 55 (2005), 561-565.) 14
stem
ball
cup
backing
Figure 3-1 Artificial hip joint. a: backing, b: cup, c: ball, d: stem
Figure 3-2 Biomaterials used in artificial hip joint. (Biomedical Engineering Handbook, Vol.1 (2000), 44-16.)
Orthopedic field: artificial hip joint Orthopedic load-bearing applications
: alumina (Al2O3), zirconia
15
Coating: artificial hip joint and dental implant
Rapid and strong fixation at
bone/titanium interface
Coating for chemical bonding with bone
(Ca10(PO4)6(OH)2, hydroxyapatite, HAp)
(bioglass)
artificial hip joint dental implant
16
Coating: processing
Currently, plasma spraying is the primary
method used commercially to fabricate a
calcium phosphate coating on dental implants.
However, plasma-sprayed calcium phosphate
coating exhibits a poor adherence to titanium
substrates and nonuniformity.
New coating
processes
17
Figure 3-3 Reconstruction of right calf bone
using b-TCP(Ca3P2O8) porous body. (H. Irie, Bull. Ceramic Soc. Jpn., 38 (2003), 57.)
Temporary bone space filler
After 18 months
b-TCP
(Tricalcium phosphate,
Ca3P2O8)
Bioresorbable or
biodegradable material
The porous b-TCP body was
substituted with bone.
18
Parameters in scaffold materials
Stability
Resorption rate
Bioactive molecules / ligands
Soluble factors
Strength
・・・・
Signaling
molecule Scaffold
Cell
Three factors required for tissue engineering
Porous calcium phosphate
tissue
engineering
19
Figure 3-4 Hydroxyapatite porous body. (M. Nakasu et al., Bull. Ceramic Soc. Jpn., 40 (2005), 828.)
Scaffold in tissue engineering
The structure of a substrate
made of synthetic materials
is needed for the growth of a
new tissue using living cells.
20
3.1 Outline of ceramic biomaterials
(2) Classification
21
Classification (1) From composition and crystalline structure
of ceramic biomaterials
Oxides alumina, zirconia,・・・
Glasses bioglass, crystallization glass,・・・
Calcium phosphates hydroxyapatite, tricalcium phosphate,・・・
In this lecture, we use the above classification.
22
Classification (2) When materials are implanted into bone, there are four types of
response at the interface between implant and bone.
Capsule:
bioinert
Implantation
Dead: toxic
Dissolved:
bioresorbable
Bonding:
bioactive
Material
bone
Figure 3-5 Response at the interface between implant and bone. 23
Classification (2) When materials are implanted into bone, there are four types of
response at the interface between implant and bone.
material: toxic
The surround tissue dies.
not practical materials
material: non-toxic and biologically inactive
A fibrous tissue of variable thickness forms.
Bioinert materials
material: non-toxic and biologically active
An interfacial bond forms.
Bioactive materials
material: non-toxic and dissolved
The surrounding bone replaces it.
Bioresorbable or Biodegradable materials
24
Classification (2) When materials are implanted into bone, there are four types of
response at the interface between implant and bone.
25
3.2 Ceramic biomaterials
(1) Oxides
26
Oxide: Alumina
Alumina: Al2O3
Excellent wear resistance
Chemically stable
ball for artificial hip joint
27
Artificial hip joint
28
Alumina: properties
(Biomaterials Science, An Introduction to Materials in
Medicine 2nd Ed. Elsevier, (2004), p.157.)
Single crystalline
alumina
99.9
3.95
392
1270
2100
0.01
29
Oxide: zirconia
Zirconia: ZrO2
Pure zirconia (ZrO2): not an engineering material
because
There are two allotropic transformations.
monoclinic ⇆ tetragonal ⇆ cubic
At around 1400 K, t-m transformation causes
4.6% volume change.
30
Pure zirconia: properties
(Biomaterials: An Introduction,
Springer, (2007), p.145.)
31
(T. Miyazaki, J. Jpn. Soc. Biomater., 25 (2007), 374.)
Zirconia: transformation
●: Zr
○: O expansion
monoclinic tetragonal cubic shrinkage
Temperature
32
Zirconia: stabilizing
Fully stabilized
zirconia
Partially stabilized
zirconia
When oxide such as CaO,
MgO or Y2O3 was added
to pure zirconia, cubic and
tetragonal phases are
stabilized.
33
Zirconia: properties
(Biomaterials: An Introduction, Springer, (2007), p.147.)
CSZ: calcia stabilized zirconia
Y-Mg-PSZ: yttria and magnesia partially stabilized zirconia
Y-TZP: yttria-stabilized tetragonal zirconia polycrystal
The fracture toughness of PSZ is larger than that of alumina
(5-6 MPa・m1/2),because
34
One of toughening mechanisms
(Biomaterials: An Introduction, Springer, (2007), p.147.)
Crack before
transformation
Crack arrestment due to
t-m transformation
(t→m: expansion!) 35
Practically, partially stabilized zirconia (PSZ) with 3mol%Y2O3
(tetragonal phase) is only commercially available.
Zirconia: current status
Wear property
Fracture toughness Zirconia > Alumina
However,
Reaction between zirconia and water ?
Zr-O-Zr + H2O Zr-OH + HO-Zr
36
3.2 Ceramic biomaterials
(2) Glasses
37
Bioactive glass ceramics
Some glass ceramics: bioactivity
A lot of bioactive glass ceramics have
been developed so far. They are
classified into two groups, that is,
bioglass (バイオガラス) and
crystallization glass (結晶化ガラス).
38
(Manual of orthopaedic materials, (1992), 49.)
Glass: structure
glass crystal
○ long-range order × long-range order
○ short-range order
39
(Handbook of ceramics, 2nd edition, application, (2002), 491)
Crystallization glass Composite of glass phase and crystalline phase
glass particles
at room temp.
Fusion of
glass particles
at 850 ℃ for 0 h.
start of crystallization
at 950 ℃ for 0 h.
end of crystallization
at 1100 ℃ for 1 h.
40
Table 3-3
A-W GC: apatite- and wollastonite-containing glass-ceramics
MB GC: machinable bioactive glass-ceramic (Biomaterials Science, An Introduction to Materials in Medicine 2nd Ed. Elsevier, (2004), p.159.)
Composition of bioactive glasses and crystallization glass
41
Bioglass
In 1971 Hench: SiO2-Na2O-CaO-P2O5
glass can bond with bone.
45S5: 45SiO2-24.5CaO-24.5Na2O-6P2O5 (mass%)
It had a great impact because such a
inorganic material has bioactivity.
(bioactivity of synthesized hydroxyapatite:
1977)
He named this material “bioglass”.
42
(Biomaterials: An Introduction, Springer, (2007), p.156.)
All compositions in region A have a
constant 6 mass% P2O5.
45S5
Compositional dependence of bioactivity
Region A: bonding in 30 days
with bone (Bioactive)
Region B: non bonding
- too low reactivity
(Bioinert)
Region C: non bonding
- too high reactivity
(Bioresorbable)
Region D: not technically
practical
43
Properties of bioglass
Advantage : high bioactivity
Application : artificial bone in middle ear
Disadvantage: poor mechanical strength
Bioactive crystallization glass
44
Bioactive crystallization glass
Composite of glass phase and crystalline phase
to increase mechanical strength
Ceravital In 1972, Brömer: SiO2-Na2O-CaO-P2O5 glass
with less Na2O contents
Crystalline phase: apatite (Ca10(PO4)6O)
Ex.
46SiO2-37.5CaO-5Na2O-11.5P2O5 (mass%)
(cf. 45S5: 45SiO2-24.5CaO-24.5Na2O-6P2O5)
Bending strength: 100 MPa >> Bioglass
45
Bioactive crystallization glass: A-W GC
To increase mechanical strength for hard tissue replacement
A-W GC(apatite and wollastonite glass ceramics) In 1982, Kokubo (Kyoto University, Japan)
SiO2-CaO-MgO-P2O5(–CaF2) glass
Crystalline phase: apatite (Ca10(PO4)6(O・F2))
wollastonite (CaSiO3)
Composition(mass%)
34.2SiO2-44.9CaO-16.3P2O5-4.6MgO-0.5CaF2
Bending strength: 220 MPa >> Ceravital
46
Strength of glass ceramics
(バイオマテリル, (2008), 101.)
47
Figure 3-6 TEM image of microstructure of A-W GC. (Manual of orthopaedic materials, (1992), 51.)
A-W GC: microstructure
White: glass phase
Grey and Black:
two crystalline phases
Small crystallites
dispersed in glass
matrix
48
A-W GC: bioactivity
Figure 3-7 TEM image of the interface between A-W GC
and bone after implantation for 8 weeks in tibia in rat. (Manual of orthopaedic materials, (1992), 51.)
Apatite phase formed at the
interfacial bonding
Bonding via apatite
(アパタイトを介した結合)
A: bone
B: apatite (hydroxyapatite)
C: A-W GC
49
A-W GC: apatite formation on surface
Figure 3-8 Apatite formation on A-W GC in body fluid.
(Manual of orthopaedic materials, (1992), 86.)
Dissolution of Ca2+ ion or HSiO3- ion might be important:
Ca2+ ion : increase in supersaturation of apatite in body fluid
HSiO3- ion : surface charge to positive
50
3.2 Ceramic biomaterials
(3) Calcium phosphates
51
(a) Calcium phosphate as biomaterials
52
(Structure and Chemistry of the Apatite and Other Calcium Orthophosphates, (1994), 49.)
Figure 3-9
Phase diagram of CaO-P2O5 system
53
Calcium phosphates as biomaterials
54
(Structure and Chemistry of the Apatite and Other Calcium Orthophosphates, (1994), 8.)
Table 3-1
Thermodynamic data of calcium phosphates
55
Important calcium phosphates as biomaterials
Hydroxyapatite: Ca10(PO4)6(OH)2
bioactive
can directly bond to bone
b type tricalcium phosphate: b-Ca3P2O8
bioresorbable
Octacalcium phosphate: Ca8H2 (PO4)6 ・5H2O
Amorphous calcium phosphate (ACP)
may be precursor of hydroxyapatite in body
56
(b) Hydroxyapatite
57
Hydroxyapatite, HAp
The most important ceramic biomaterials
Why?
HAp can bond with bone at the atomic scale.
Why?
58
(Introduction of the human body 6th Ed.,
(2004), 118, 482.)
Cross section of bone and tooth
59
Microstructure of bone
(T. Kokubo et al., Bull. Ceramic Soc. Jpn., 38 (2003), 2.)
bone
osteon
concentric lamellae
(3-7 mm) collagen fiber
biological apatite
(length: 20-49 nm)
60
inorganic component
Bone and tooth (hard tissue): organic component
water
Table 3-2 Component in tooth and bone (mass%).
61
(Hydroxyapatite and related materials, CRC, (1994), 6.)
Components of hard tissues
Components of hard tissues
(Structure and Chemistry of the Apatite and Other Calcium Orthophosphates, (1994), 260.)
inorganic component
Bone and tooth (hard tissue): organic component
water
Component Enamel Dentine Bone Ca 37.6 40.3 36.6 P 18.3 18.6 17.1
CO2 3.0 4.8 4.8 Na 0.7 0.1 1.0 K 0.05 0.07 0.07 Mg 0.2 1.1 0.6
Sr 0.03 0.04 0.05 Cl 0.4 0.27 0.1 F 0.01 0.07 0.1
Ca/P(molar) 1.59 1.67 1.65
Table 3-3 Inorganic component in tooth and bone (mass%).
Inorganic
component
Calcium
phosphate
Biological
apatite
62
Biological apatite
Structure: Hydroxyapatite (Ca10(PO4)6(OH)2) type
Chemical composition: (Ca, Na, Mg, K, X)10(PO4, CO3, HPO4)6(OH, Cl, F)2
X = trace elements such as Sr
63
Sr: introduce to bone (99%)
In nuclear power generation: 235U → 90Sr(→90Y→ 90Zr)
half-life of 90Sr: 28.8 years half-life of 90Y: 64 hours
yield of 90Sr: 5.75 %
Hydroxyapatite, HAp
The bone mainly consists of collagen fiber and
biological apatite. The composition and structure
of biological apatite are very close to those of
hydroxyapatite.
Bioactivity
(Bonding to bone)
In the 1970s, direct bonding with bone was discovered.
Hydroxyapatite
64
HAp
Interface between HAp and new bone
New bone (Handbook of ceramics, 2nd edition, application, (2002), 1512.) 65
Bonding to bone
P.-I. Brånemark
1952年:チタンと骨が結合することを発見
L. Hench
1969年:骨と結合するガラス発見
人工物であるハイドロキシアパタイトは骨と化学的に結合 (1974年)
(ハイドロキシアパタイト:生体アパタイトと同じ結晶構造・近い組成)
実はハイドロキシアパタイトを介した結合 66
Bioactivity of HAp: osteoconductivity
骨伝導性: 骨形成細胞存在下において、
その場で新生骨を形成させる特性
Osteoconductivity: bone forming ability
under the conditions with osteogenic cells
骨誘導性: 本来骨形成細胞の存在しない部位において新生骨を形成する特性
Osteoinductivity: bone forming ability under
the conditions without osteogenic cells 67
(c) Anisotropy of hydroxyapatite
68
(Structure and Chemistry of the Apatite and Other Calcium Orthophosphates, (1994), 73.)
Crystallographic structure of HAp
69
Crystallographic structure of HAp
hexagonal structure
OH ion aligned (001) direction
two sites for Ca ion
Columnar site Ca(1)
Screw axis site Ca(2)
Ca(2)6Ca(1)4(PO4)6(OH)2
70
Anisotropy of HAp
a face
c face
Atomic arrangements on a and
c faces are completely different.
Anisotropy in crystallographic face of HAp
Mechanical properties
Adsorption of molecules
Dissolution in acid solution 71
Anisotropy in mechanical property of HAp
(Hoepfner and Case, Mat. Lett., 58 (2004), 489.)
Lack of the data on mechanical and chemical anisotropy of HAp
because of
the difficulty in fabrication of big HAp single crystals
Thermal expansion data
72
Anisotropy in bone
bone
Stress
direction
c axis of biological apatite
crystallites is oriented to the
stress induced direction.
c axis
73
Anisotropy in enamel of tooth
Enamel consists of apatite
crystals.
(1) The c face of the apatite
crystals is oriented to the
outside.
(2) The crystallinity of the
apatite crystals is much
higher than that of bone.
c axis
c axis c axis
c axis
74
Crystallinity of enamel of tooth
Enamel
(block)
Enamel
(powder)
Dentine
Bone
75
Apatite
(002)
(d) Solubility of calcium phosphate
76
Fig. 3-10 Solubility of calcium phosphates in aqueous system.
Solubility of calcium phosphate
HAp: most stable calcium phosphate in body fluid
main inorganic component of bone
hydroxyapatite, Ca10(PO4)6(OH)2
High
Low
Tetracalcium phosphate, Ca4P2O9
a-tricalcium phosphate, a-Ca3P2O8
b-tricalcium phosphate, b-Ca3P2O8
Octacalcium phosphate, Ca8H2(PO4)6・5H2O Solubility
77
Solubility products
Solubility product (溶解度積): Ks
The solubility product of HAp(Ca10(PO4)6(OH)2) in aqueous
solution can be expressed by
ai: activity of i (=gi×[ i ])
gi: activity coefficient of i
[ i ]: concentration of i in mole/L
Ks = a10 ・a6 ・a2 Ca2+ PO4
3- OH-
78
Value of solubility products of HAp in aqueous solution
79
●gi: evaluated using Debye-Hückel model
g : 0.36 Ca2+
g : 0.06
g : 0.72 PO4
3-
OH-
Ks = 5.5 × 10-118 at 410 K
●Body fluid: supersaturated to HAp
K. Hata et al., J. Am. Ceram. Soc., 78 (1995) 1049.
s = = S – 1 > 0 IP - Ks Ks
IP: ionic activity product of body fluid
s: relative supersaturation
S: supersaturation ratio
Effect of temperature on solubility of apatite in aqueous system
80
Fig. 3-11 Solubility of Ca10(PO4)6(OH)2 in the system Ca(OH)2-H3PO3-H2O.
Figure 3-12 Solubility of calcium phosphates in Ca(OH)2-H3PO4-H2O system at 310 K.
(村上ら: バイオマテリアル, 28 (2010) 274-280.)
Effect of pH on solubility of calcium phosphate
81
HAp: low solubility,
not bioresorbable material
-TCP: the most common
bioresorbable material
Bioresorbable material
The moderate solubility
is required for the
bioresorbable materials.
hydroxyapatite, Ca10(PO4)6(OH)2
Solubility
High
Low
Tetracalcium phosphate, Ca4P2O9
a-tricalcium phosphate, a-Ca3P2O8
b-tricalcium phosphate, b-Ca3P2O8
Octacalcium phosphate, Ca8H2(PO4)6・5H2O
82
(e) Applications
83
HAp dense HAp porous β-TCP porous
(M. Kawashita, J. Jpn. Soc. Biomater., 25 (2007), 393.)
Applications of calcium phosphates
Dense and porous
calcium phosphate
Bone space filler
scaffold Table 3-4 Properties of calcium phosphates for bone space filler
porous dense porous porous dense Morphology
Porosity
pore size
bend.stren.
comp.stren.
Composition
84