500 μm

TMS Tutorial on TMS Tutorial on Biology for Materials Scientists and EngineersBiology for Materials Scientists and Engineers

February 25, 2007February 25, 2007

Fracture and Fatigue of Biological Fracture and Fatigue of Biological Materials: Bone and Teeth Materials: Bone and Teeth

Robert O. RitchieRobert O. Ritchie

Work supported at the Lawrence Berkeley National Laboratory Work supported at the Lawrence Berkeley National Laboratory by the National Institutes of Health under Grant Nos. 5R01DE0156by the National Institutes of Health under Grant Nos. 5R01DE015633 and 33 and P01DE09859P01DE09859

and by the Department of Energy under Contract No. DEand by the Department of Energy under Contract No. DE--AC03AC03--76SF0009876SF00098www.LBL.govwww.LBL.gov/Ritchie/Ritchie

Materials Sciences Division,Materials Sciences Division, Lawrence Berkeley National LaboratoryLawrence Berkeley National Laboratoryand Department of Materials Science and Engineeringand Department of Materials Science and Engineering

University of California, BerkeleyUniversity of California, Berkeley

150 μm

The Problem!The Problem!

•• 1 in 2 women & 1 in 4 men over 50 will have an osteoporosis1 in 2 women & 1 in 4 men over 50 will have an osteoporosis--related related bone fracture over their remaining lifetimebone fracture over their remaining lifetime

•• problem treated in terms of loss of bone mass (problem treated in terms of loss of bone mass (bone quantitybone quantity), but this is ), but this is only a part of the problem only a part of the problem –– the other issue is the other issue is bone qualitybone quality

1010--fold increase in fracture fold increase in fracture risk foundrisk found with aging, independent of bone mineral densitywith aging, independent of bone mineral density

(from: www.emedx.com)

10 μm

failures in failures in bone from bone from impact or impact or fatigue fatigue (stress (stress fractures)fractures)

500 μm

osteoporoticosteoporotic trabeculartrabecular bonebone

bone damaged bone damaged by steroidsby steroids

CXTCXT

mCTmCT

SEMSEM

•• 10 million people in the U.S. have osteoporosis10 million people in the U.S. have osteoporosis

bone turnoverbone turnoverfatigue damagefatigue damage

abnormal abnormal mineralization, etcmineralization, etc.

Bone Quality?Bone Quality?

AgingAgingDiseaseDiseaseTherapyTherapy

Risk of Risk of Fracture?Fracture?

Structure Structure of Boneof Bone(molecular to

macro)

?Physical Physical mechanismsmechanisms of of

damagedamagefracturefracture

tougheningtoughening

Quantitatively Quantitatively assess in terms assess in terms of the fracture of the fracture toughness, toughness, KKcc

OutlineOutline

•• IntroductionIntroduction-- structural length scales in bonestructural length scales in bone

•• Criteria for fractureCriteria for fracture-- fracture toughnessfracture toughness

-- toughening mechanismstoughening mechanisms

•• Aging, disease and treatmentAging, disease and treatment-- effect of aging & diseaseeffect of aging & disease

-- therapeutic treatmentstherapeutic treatments

•• Assessment of bone qualityAssessment of bone quality-- fracture mechanics testingfracture mechanics testing

-- crack path (in bone biopsies)crack path (in bone biopsies)

hydrated collagen (40 MPa)

acetone (1.2 GPa)

rehydrated collagen (30 MPa)

0 100 200 300 400 500DEPTH (nm)

0

20

40

60

80

100

LOA

D (μ

Ν)

1 μm 0.1 μm

AFMAFM--based based picoindentationpicoindentation

10 μm

GC

M

M5 μm

150 μm

What Controls Fracture in Materials?What Controls Fracture in Materials?

10 μm

ceramicsceramics

bonebone•• fracture in cortical bone shares many fracture in cortical bone shares many

commonalities with structural ceramics, commonalities with structural ceramics, i.e.,i.e.,the importance of extrinsic toughening the importance of extrinsic toughening mechanisms, principally crack bridging, and mechanisms, principally crack bridging, and resultant resistanceresultant resistance--curve (Rcurve (R--curve) behaviorcurve) behavior

4 μm

Fracture is a mutual competition Fracture is a mutual competition between:between:

•• intrinsic damage mechanismsintrinsic damage mechanismsahead of the crack tip, that promote ahead of the crack tip, that promote crack propagation, andcrack propagation, and

•• extrinsic toughening (shielding) extrinsic toughening (shielding) mechanismsmechanisms behind the crack tip, behind the crack tip, that inhibit crack propagationthat inhibit crack propagation

Ritchie, Ritchie, Mat. Sci. EngMat. Sci. Eng., 1988; ., 1988; Int. J. Fract.Int. J. Fract., 1999, 1999

•• building blocks:building blocks: collagen & nanocollagen & nano--crystalline hydroxyapatite mineral crystalline hydroxyapatite mineral

•• at nanometer scale:at nanometer scale: mineralized mineralized collagen fibrils collagen fibrils

•• at micron scale:at micron scale: lamellae structure lamellae structure of collagen fibersof collagen fibers

•• at micron scaleat micron scale in dentinin dentin:: tubulestubules•• at hundreds of micronsat hundreds of microns in bonein bone::

osteonsosteons/ Haversian canals/ Haversian canals

•• at macro scale:at macro scale: size and type of the size and type of the tooth or bonetooth or bone

Structural Length Scales in Teeth & BoneStructural Length Scales in Teeth & Bone

Complex, hierarchical structuresComplex, hierarchical structures

At what length scales At what length scales do changes occur that do changes occur that lead to fracture risk?lead to fracture risk?

1 μm

BoneBone

DentinDentin

DentinDentin is:is:45 45 volvol% apatite% apatite30 30 volvol% collagen% collagen25 25 volvol% fluid% fluid

1 μm

Nature of Inelasticity in Mineralized TissueNature of Inelasticity in Mineralized Tissue

Inelastic deformation results from:Inelastic deformation results from:

•• plastic deformation (in the collagen fibrils)plastic deformation (in the collagen fibrils)

•• microcrackingmicrocracking damage (at the damage (at the peritubularperitubularcuffs and in the cuffs and in the intertubularintertubular matrix)matrix)

•• poroporo--elasticity (from fluid in the tubules)?elasticity (from fluid in the tubules)?

2.8 3.2 3.6 4.0 4.4 4.8LOAD-LINE DISPLACEMENT (mm)

0

1

2

3

4

5

6

7

LOAD

(N)

HUMAN DENTIN25o C, HANK'S BSS

0

NallaNalla, Kinney & Ritchie, , Kinney & Ritchie, J. J. BiomedBiomed. Mater. Res.. Mater. Res., 2003, 2003

•• uniaxialuniaxial tensile test in human dentintensile test in human dentin (a)

100 μm

10 μm

10 μm 10 μm

•• fracture toughness assessed using fracture toughness assessed using crackcrack--resistance curves (Rresistance curves (R--curves)curves)

Time (t)

calculatedcrack length

Cra

ck L

engt

h (a

)

Stress-intensity Range (∆K)

fatigue-crack growth data

Cra

ck G

row

th R

ate

(da/

dN)

Experimental MeasurementsExperimental Measurements

0 0.5 1 1.5 2 2.5LOAD LINE DISPLACEMENT, δ (mm)

0

4

8

12

16

20

LOAD

, P (l

bs)

Stre

ss-in

tens

ity (K

)

Crack extension, (∆a)

R-curve

Load-line Displacement

⇓Data

Recorder⇓

Computer Controlling

System

LVDT

Normalized Crack Length

(a/W)

calibrationcurve

Load

-line

D

ispl

acem

ent

Fatigue crackFatigue crack--growth ratesgrowth ratesFracture toughness, Fracture toughness, KKcc

C(T)

•• fatiguefatigue--crack growth assessed using crack growth assessed using da/dNda/dN vs. vs. ΔΔKK plots (plots (vv--KK curves)curves)

Kc = Q σF (πa)½

where where σσFF = fracture stress= fracture stressaa = crack size= crack sizeQQ = geometry factor ~1= geometry factor ~1

Fracture MechanicsFracture Mechanics

Mechanisms of Fracture InitiationMechanisms of Fracture Initiation•• two identical notches in a two identical notches in a

fourfour--point bend barpoint bend bar•• constant bending moment constant bending moment

on both notcheson both notches•• one notch breaks one notch breaks -- the other the other

freezes freezes local fracture events local fracture events just prior to fracturejust prior to fracture

•• crack initiation directly crack initiation directly atat the notch root implies that the notch root implies that initiation initiation of fractureof fracture in human cortical bone and dentin is locally in human cortical bone and dentin is locally strainstrain--controlledcontrolled Nalla, Kinney & Ritchie, Nalla, Kinney & Ritchie, Nature MatNature Mat., 2003; ., 2003; J. J. BiomedBiomed. Mater. Res.. Mater. Res., 2003, 2003

with inelasticity, stresses peak ahead of notch, strains peak atwith inelasticity, stresses peak ahead of notch, strains peak at notchnotch

doubledouble--notch fournotch four--point bend testpoint bend test 1 mm

1 μm

Notch surface

1 μm

Notch surface

SEMSEM

Distance ahead of notch, normalized by the notch-root radius

PD:PD: pressurepressure--insensitive insensitive plasticityplasticity

BD:BD: pressurepressure--sensitive sensitive microcrackingmicrocrackinginelasticityinelasticity

Fracture Toughness of Human BoneFracture Toughness of Human Bone

•• marked effect of orientation on toughness, marked effect of orientation on toughness, i.e.,i.e., resistance to resistance to fracture, due to anisotropic nature of microstructure fracture, due to anisotropic nature of microstructure

•• much higher toughness in transverse orientation due to much higher toughness in transverse orientation due to crack deflection along the cement lines (crack deflection along the cement lines (osteonosteon interfaces)interfaces)

•• ““stressstress--raisersraisers”” are not necessarily bad are not necessarily bad –– itit’’s the overall s the overall crack path that matters!crack path that matters! Nalla, StNalla, Stöölken, Kinney & Ritchie, lken, Kinney & Ritchie, J. Biomechanics,J. Biomechanics, 20052005

Anti-planelongitudinal

In-planelongitudinal

Transverse Transverse

1 mm

1 mm

1 mm

transversetransverse

longitudinal (mediallongitudinal (medial--lateral)lateral)longitudinal (proximallongitudinal (proximal--distal)distal) SEMSEM

•• bone is tougher in certain directionsbone is tougher in certain directions•• it is much more difficult to break than to splitit is much more difficult to break than to split•• it is a factor of two tougher in the transverse orientationit is a factor of two tougher in the transverse orientation

44--point point bendbend

osteonsosteons interfaces are sites of preferred crackinginterfaces are sites of preferred cracking

W

Kc = Q σF (πa)½

0

1

2

3

4

5

6

FRAC

TUR

E TO

UG

HN

ESS,

Kc

(MPa

√m)

HUMAN CORTICAL BONE25°C, Wet

2.2

MP

a√m

3.5

MPa

√m

5.3

MPa

√m

compactcompact--tensiontension

transversetransverse

longitudinallongitudinal

humeral cortical bonehumeral cortical bone

0 100 200 300 400 500 6000

2

4

6

8

10

ST

RES

S IN

TEN

SITY

, K, (

MPa

√m)

CRACK EXTENSION, Δa, (μm)

in situin situ loading in SEMloading in SEM

RR-- curvecurve

Koester, Koester, AgerAger, & Ritchie, 2006, & Ritchie, 2006

10 10 μμmmHuman cortical boneHuman cortical bone

0 100 200 300 400 500 6000

2

4

6

8

10

STR

ESS

INTE

NSI

TY, K

, (M

Pa√m

)

CRACK EXTENSION, Δa, (μm)

0 100 200 300 400 500 6000

2

4

6

8

10

ST

RES

S IN

TEN

SITY

, K, (

MPa

√m)

CRACK EXTENSION, Δa, (μm)

0 100 200 300 400 500 6000

2

4

6

8

10

STR

ESS

INTE

NSI

TY, K

, (M

Pa√m

)

CRACK EXTENSION, Δa, (μm)

0 100 200 300 400 500 6000

2

4

6

8

10

ST

RES

S IN

TEN

SITY

, K, (

MPa

√m)

CRACK EXTENSION, Δa, (μm)

Crack DeflectionCrack Deflection

Constrained Constrained MicrocrackingMicrocracking

UncrackedUncracked--Ligament BridgingLigament Bridging

CollagenCollagen--FibFibrilril BridgingBridging

3.0 3.0 MPaMPa√√mm(transverse)

k1(α) = c11(α) KI + c12(α) KIIk2(α) = c21(α) KI + c22(α) KII

Kd = (k12 + k22)1/2

(Bilby et al., 1978; Cottrell & Rice, 1980)

Kmic = 0.22 εmE′fm lm1/2+ β fmKc(Evans & Fu, 1985: Hutchinson, 1987)

Kbul = -fulKI[(1+lu/rb)1/2-1] /

[1-ful+ful(1+lul/rb)1/2] (Shang & Ritchie, 1989)

Kbf = 2 σb ff (2 lf / π)-1/2

(Evans & McMeeking, 1986)

Contribution to Contribution to ToughnessToughness

0.1 0.1 MPaMPa√√mm(medial-lateral)

11--1.5 1.5 MPaMPa√√mm(proximal-distal)

~0.05 ~0.05 MPaMPa√√mm

Nalla, Kinney & Ritchie, Nalla, Kinney & Ritchie, Nature Mat.Nature Mat., 2003; , 2003; NallaNalla, , StStöölkenlken, Kinney & Ritchie, , Kinney & Ritchie, J BiomechanicsJ Biomechanics, 2005, 2005

collagenfibers

crack tipuncracked ligament

bridgescrack tipuncracked ligament

bridges

microcracks

unmicrocrackedmaterial

osteons

100 μm

1 μm

10 μm

100 μm)

SEMSEM

Origins of Toughening in BoneOrigins of Toughening in Bone

•• cracks in harder enamel do cracks in harder enamel do not necessarily break the not necessarily break the tooth as they arrest tooth as they arrest ““atat”” the the dentindentin--enamel junction (DEJ) enamel junction (DEJ)

•• cracks arrest when they form cracks arrest when they form elastic bridges in the (mantle) elastic bridges in the (mantle) dentin due to the formation of dentin due to the formation of uncrackeduncracked ligaments in the ligaments in the crack wakecrack wake

EnamelEnamel

DentinDentin

DEJDEJ

uncracked ligament bridginguncracked ligament bridging

ImbeniImbeni, , KruzicKruzic, Marshall, Marshall & Ritchie, , Marshall, Marshall & Ritchie, Nature Mat.,Nature Mat., 20052005

DentinDentin EnamelEnamel

SEMSEM

SEMSEM

50 μmopticaloptical

Crack Arrest in the DEJ Region in TeethCrack Arrest in the DEJ Region in Teeth

Toughness of the DEJ Region in TeethToughness of the DEJ Region in Teeth

•• upperupper--bound toughness of the DEJ bound toughness of the DEJ estimated to beestimated to be GGc,DEJc,DEJ ~ ~ 115 J/m115 J/m22

•• toughness of the DEJ is intermediate toughness of the DEJ is intermediate between enamel and dentin between enamel and dentin

•• it is ~5it is ~5--10 times higher than enamel 10 times higher than enamel but still 75% of dentinbut still 75% of dentin

•• Toughness of the DEJ Toughness of the DEJ assessed from the elastic assessed from the elastic mismatch between dentin and mismatch between dentin and enamel by whether the crack enamel by whether the crack deflects, arrests or penetrates deflects, arrests or penetrates the interfacethe interface after Sun, Becher et al.

1

2

1

2

0.75

He and Hutchinson (1989)

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

-1.5 -1 -0.5 0 0.5 1 1.5 2 2.5 3

Distance of indent from D.E.J (mm)

Har

dnes

s(V

icke

rs)

(GP

a) dentin

enamel

115154~ 250.532064

Gc,DEJ(J/m2)

Gc,dentin(J/m2

Gc,enamel(J/m2)

α E′ dentin(GPa)

E′enamel(GPa)

Elastic mismatch:Elastic mismatch:αα = (= (EE11--EE22)/()/(EE11++EE22))

ImbeniImbeni, , KruzicKruzic, Marshall, Marshall & Ritchie, , Marshall, Marshall & Ritchie, Nature Mat.,Nature Mat., 20052005

Gc,DEJ/ Gc,dentin ~ 0.75

50 μm

Experimental Proof of Crack BridgingExperimental Proof of Crack Bridging

Pbr

Experimental: crack

2.88 2.92 2.96 3.00LOAD-LINE DISPLACEMENT (mm)

1

2

3

4

5

6

7

8

APPL

IED

LO

AD (N

)Experimental: mechanical slot Theoretical: traction-free crack

human cortical bonehuman cortical bone

•• compliance of actual crack is measured before and after machinincompliance of actual crack is measured before and after machining the wake; g the wake; results compared to theoretical compliance of tractionresults compared to theoretical compliance of traction--free crack (of same length)free crack (of same length)

•• bbridging contribution to toughnessridging contribution to toughness of bone measured atof bone measured at KKbrbr ~ 0.5 ~ 0.5 –– 1 1 MPaMPa√√mm, and , and occurs over large length scales (hundreds of microns)occurs over large length scales (hundreds of microns)

Kruzic, Nalla, Kinney & Ritchie, Kruzic, Nalla, Kinney & Ritchie, Biomaterials, Biomaterials, 20042004

multimulti--cutting compliancecutting compliance500 μm

500 μm

crack bridging in human crack bridging in human cortical bone verified using a cortical bone verified using a ccomplianceompliance--based techniquebased technique

22--D D tomographictomographic slices slices of of uncrackeduncracked--ligament ligament bridged cracks in dentinbridged cracks in dentin

CXTCXT

Crack Bridging vs. Constrained Crack Bridging vs. Constrained MicrocrackingMicrocracking

•• microcracking based explanation for toughening prevalent in the microcracking based explanation for toughening prevalent in the literatureliterature•• crack bridging will reduce compliance, crack bridging will reduce compliance, CC;; microcracking will increase compliancemicrocracking will increase compliance•• supports bridging as the main toughening mechanism, rather than supports bridging as the main toughening mechanism, rather than microcrackingmicrocracking

Nalla, Kruzic, Kinney & Ritchie, Nalla, Kruzic, Kinney & Ritchie, Bone, Bone, 20042004

LOAD LINE DISPLACEMENT, δ

LOAD

, P

bridged crack(less compliant)

bridge andmicrocrack free crack

microcracktoughened crack(more compliant)

1/C

bridged crack(less compliant)

bridge and microcrack free crack

microcracktoughened crack(more compliant)

1/C microcracks

unmicrocracked material

crack tipuncracked ligament

bridgescrack tipuncracked ligament

bridges

0 0.1 0.2 0.3 0.4LOAD LINE DISPLACEMENT, δ (mm)

0

10

20

30

40

LOA

D ,

P (l

bs)

computed tractionfree compliance

Δa = 4.8 mm

measured complianceΔa = 4.8 mmmeasured compliance

Δa = 4.8 mm

computed traction free complianceΔa = 4.8 mm

TomographicTomographic Evidence of Crack BridgingEvidence of Crack Bridging

Nalla, Kruzic, Kinney & Ritchie, Nalla, Kruzic, Kinney & Ritchie, BiomaterialsBiomaterials, 2005, 2005Kruzic, Nalla, Kinney & Ritchie, Kruzic, Nalla, Kinney & Ritchie, Biomaterials, Biomaterials, 2003;2003;

XX--Ray Computed Tomography, Ray Computed Tomography, performed at the Stanford performed at the Stanford Linear Accelerator Center and Linear Accelerator Center and Advanced Light Source (LBNL) Advanced Light Source (LBNL)

human dentinhuman dentin human cortical bonehuman cortical bone

Haversiancanals

crack

uncrackedligaments

20 μm CXTCXT

250 μm CXTCXT

1mm (ii) (iii) (iv) (i)

500 μm (ii)

500 μm (iii) 500 μm (iv)

(i) 500 μm

1mm

(i) (ii) (iv)(iii)

(i) 500 μm

(iv) 500 μm

500 μm(ii)

(iii) 500 μm

hydrated dentinhydrated dentin dehydrated dentindehydrated dentin

uncrackedligaments

ResistanceResistance--Curve Toughness BehaviorCurve Toughness Behavior

•• presence of crackpresence of crack--bridging does result in bridging does result in crackcrack--size dependent size dependent behavior:behavior:

-- rising Rrising R--curves curves

-- smallsmall--crack effectscrack effects

0 2 4 6 8CRACK EXTENSION, Δa (mm)

0

2

4

6

STR

ESS

INTE

NSI

TY, K

(MPa

√m)

HUMAN CORTICAL BONEHBSS, 25oCDonor: 34-41yrs.

cortical bone 0 2 4 6CRACK EXTENSION, Δa (mm)

0

1

2

3

4

STR

ESS

INTE

NSI

TY, K

(MPa

√m)

hydrated in Hank's solution

dehydrated in vacuo

hydrated in HBSS

dentin

(a)

traction-free crack

zone of nonlinear,damaged material

(b)

idealized planar cracktractions p(u)

2ωb(x1)

x1a00

bridging or cohesive zoneλb

crack tip2u

A

a

A

•• as bridging zones are ~hundreds of as bridging zones are ~hundreds of microns in size, they can be microns in size, they can be comparable with the size of the bone comparable with the size of the bone (or tooth) (or tooth) -- quoted (singlequoted (single--value) value) KKIcIcfracture toughness values are thus fracture toughness values are thus likely sizelikely size-- and geometry dependentand geometry dependent

CohesiveCohesive--zone zone modelingmodeling

ResistanceResistance--curves curves

NallaNalla, , KruzicKruzic & Ritchie, & Ritchie, BoneBone, 2004, 2004KruzicKruzic, , NallaNalla, Kinney & Ritchie, , Kinney & Ritchie, Biomaterials, Biomaterials, 20032003 QangQang, Cox, , Cox, NallaNalla & Ritchie,& Ritchie, Biomaterials, 2006; BoneBiomaterials, 2006; Bone, 2006, 2006

Fatigue of Mineralized TissueFatigue of Mineralized Tissue

•• not clear whether this is a cyclenot clear whether this is a cycle-- or timeor time--dependent phenomenon dependent phenomenon

•• ““metalmetal--likelike”” fatigue fatigue S/NS/N behavior with frequencybehavior with frequency--dependent fatigue limit at 10dependent fatigue limit at 1066--101077

cycles of ~25 and 45 cycles of ~25 and 45 MPaMPa

•• comparable at lower frequency to typical comparable at lower frequency to typical masticatorymasticatory stress levels (~20 stress levels (~20 MPaMPa) ) •• fatigue lives, in terms of cycles to failure, are shorter at lowfatigue lives, in terms of cycles to failure, are shorter at lower frequencyer frequency

100 1000 10000 100000 1000000 10000000100000000NO. OF CYCLES (log)

0

10

20

30

40

50

60

70

STR

ESS

AMPL

ITU

DE

(MPa

)

2 Hz20 Hz

HUMAN DENTINR = 0.1 25oC, HANK'S BSS

σa

σmax

σmin

σm

102 103 104 105 106 107 108

, Nf, σ

a (M

Pa)

NallaNalla, , ImbeniImbeni, Kinney, , Kinney, StaninecStaninec, Marshall & Ritchie, , Marshall & Ritchie, J. J. BiomedBiomed. Mater. Res.. Mater. Res., 2003, 2003

4 mm2 mm

Load

Enamelcorner

10 mm

0.90 mm

0.90 mm

load ratio load ratio RR = = σσminmin//σσmaxmax

•• clear evidence of premature clear evidence of premature fatigue failure of both human fatigue failure of both human teeth and boneteeth and bone

S/NS/N behaviorbehavior

•• Paris powerParis power--law relationship, dlaw relationship, daa/d/dN N == C C ΔΔKKmm, where exponent , where exponent mm ~ 8.76~ 8.76

•• estimated fatigue threshold, estimated fatigue threshold, ΔΔKKTHTH ~ 1.06 ~ 1.06 MPaMPa√√mm, ~60% of the fracture toughness, ~60% of the fracture toughness

23000 23200 23400 23600NO. OF CYCLES

0.0

0.5

1.0

1.5

2.0

2.5

3.0

MA

XIM

UM

LO

AD (N

)

HUMAN DENTIN25o C, HANK'S BSS

(b) 0

h

M

b

a

da/dN = 6.24 x 10-11 (ΔK)8.76

5 6 7 8 9 2 3 4 51STRESS-INTENSITY RANGE, ΔK (MPa√m)

10-8

10-7

10-6

10-5

10-4

CR

ACK-

GR

OW

TH R

ATE,

da/

dN (m

m/c

ycle

)

10-9

10-8

10-7

10-6

da/d

N (i

n/cy

cle)

5 6 7 8 9 2 3 41ΔK (ksi√in)

HUMAN DENTINR = 0.125°C, Hank's BSS

•• decay in stiffness used decay in stiffness used to estimate crack to estimate crack lengths from smoothlengths from smooth--bar bar S/NS/N teststests

NallaNalla, , ImbeniImbeni, Kinney, , Kinney, StaninecStaninec, Marshall & Ritchie, , Marshall & Ritchie, J J BiomedBiomed Mater ResMater Res, 2003, 2003

FatigueFatigue--Crack Growth in Human DentinCrack Growth in Human Dentin

FatigueFatigue--Crack Growth Data in DentinCrack Growth Data in Dentin

• effect of frequency seen in effect of frequency seen in ““per cycleper cycle”” & & ““per timeper time”” data from 1data from 1--50 Hz50 Hz

•• as in many materials, growth rates depend upon both as in many materials, growth rates depend upon both ΔΔKK and and KKmaxmax

10-4

10-5

10-6

10-7

10-8

10-9

10-10

10.90.80.70.60.5

STRESS-INTENSITY RANGE, ΔK (MPa√m)

CR

AC

K G

RO

WTH

RAT

E, d

a/dN

(m/c

ycle

)

ELEPHANT DENTIN37OC, HBSS, R=0.1

10 Hz1 Hz

50 Hz

10.90.80.70.60.5

MAXIMUM STRESS INTENSITY, Kmax (MPa√m)

CR

AC

K G

RO

WTH

RA

TE, d

a/dt

(m/s

)

ELEPHANT DENTIN37OC, HBSS, R=0.1

10 Hz1 Hz

50 Hz

10-4

10-5

10-6

10-7

10-8

10-9

10-10

da/dN ∝ ΔKm

m ~ 12-30

KruzicKruzic, , NallaNalla, Kinney & Ritchie, , Kinney & Ritchie, Biomaterials, Biomaterials, 20052005

•• crack tends to blunts under static loadingcrack tends to blunts under static loading•• crack crack ““sharpenssharpens”” under cyclic loadingunder cyclic loading

Cyclic/Static Loading Experiments in DentinCyclic/Static Loading Experiments in Dentin

ELEPHANT DENTIN37OC, HBSSKmax=1 MPa√m

0 2000 4000 6000 8000TIME (s)

0

0.25

0.5

0.75

1

CR

AC

K E

XTE

NS

ION

(mm

)

A B

C 1

0.9

fati-gue

sustainedload

fatigue

A

50 μm

B

50 μm

C

50 μm

KruzicKruzic, , NallaNalla, Kinney & Ritchie, , Kinney & Ritchie, Biomaterials, Biomaterials, 20052005

•• at constant at constant KKmaxmax, crack barely propagates when unloading cycle is removed, crack barely propagates when unloading cycle is removed

•• clear evidence of clear evidence of cyclecycle--dependent dependent fatigue mechanismfatigue mechanism

•• also evidence of a also evidence of a deterioration in the deterioration in the fraction of bridging fraction of bridging ligaments ligaments

50 μm

Fatigue vs. Slow Crack Growth in BoneFatigue vs. Slow Crack Growth in Bone

•• high growth rates high growth rates –– timetime--dependent static dependent static mechanisms (creepmechanisms (creep--dominated) dominated)

•• low growth rates low growth rates –– cyclecycle--dependent fatigue dependent fatigue mechanisms (fatiguemechanisms (fatigue--dominated)dominated)

•• crack growth by alternating blunting & crack growth by alternating blunting & resharpeningresharpeningand cycleand cycle--induced damage of bridging ligamentsinduced damage of bridging ligaments

Nalla, Kruzic, Kinney & Ritchie, Nalla, Kruzic, Kinney & Ritchie, Biomaterials, Biomaterials, 20052005

1.65

1.5

HUMAN CORTICAL BONE37OC, HBSSKmax=1.65 MPa√m

0 200 400 600 800 1000TIME (s)

0

0.5

1

1.5

2

2.5

3

CR

AC

K E

XTE

NS

ION

(mm

)

1

0.9

0 200000 400000 600000 800000 1000000TIME (s)

0

0.5

1

1.5

2

CR

ACK

E XT E

NSI

ON

( mm

)

HUMAN CORTICAL BONE37OC, HBSSKmax=1 MPa√m

crackcrack--tip bluntingtip blunting

10-3

10-4

10-5

10-6

10-7

10-8

10-9

10-10

0.1 1 100.2 0.3 0.4 0.5 0.60.70.80.9 2 3 4 5 6 7 8 9

MAXIMUM STRESS INTENSITY, Kmax (MPa√m)

CR

AC

K-G

RO

WTH

RA

TE, d

a/dt

(m/s

)

HUMAN CORTICAL BONE37OC, HBSS

Fatigue (experimental)

Static (experimental)

Fatigue (predicted)

dtftKKKCdNda p

f

)]2sin(22

[/1

0

minmax πΔ+

+= ∫

Evans & Fuller, 1974

•• small surface cracks (~70small surface cracks (~70--1000 1000 μμm) grow faster than large m) grow faster than large (through(through--thickness) cracks thickness) cracks (> 2 mm) at the same (> 2 mm) at the same ΔΔKK

•• such microcracks grow such microcracks grow intermittently and locally arrest intermittently and locally arrest at microstructural features, e.g., at microstructural features, e.g., at the at the osteonosteon structuresstructures

Fatigue of Small Surface CracksFatigue of Small Surface Cracks

KruzicKruzic, Scott, , Scott, NallaNalla, & Ritchie, , & Ritchie, J. Biomechanics, J. Biomechanics, 20062006

•• their faster growth rates can be attributed their faster growth rates can be attributed to their limited wake, which restricts the to their limited wake, which restricts the development of crack bridgingdevelopment of crack bridging

small cracksmall crack large cracklarge crack

•• limiting conditions for fatigue failure limiting conditions for fatigue failure can be defined by the fatigue can be defined by the fatigue threshold threshold ΔΔKKTHTH at large crack sizes at large crack sizes (> 150 (> 150 μμm) and by the smoothm) and by the smooth--bar bar fatigue limit fatigue limit ΔσΔσfatfat at small crack at small crack sizessizes

Kitagawa Diagram for Fatigue of DentinKitagawa Diagram for Fatigue of Dentin

KruzicKruzic & Ritchie, & Ritchie, J. Biomedical Materials Research, J. Biomedical Materials Research, 20062006

100 1000 10000 100000 1000000 10000000100000000NO. OF CYCLES (log)

0

10

20

30

40

50

60

70ST

RES

S AM

PLIT

UD

E (M

Pa)

2 Hz20 Hz

HUMAN DENTINR = 0.1 25oC, HANK'S BSS

σa

σma

x

σmin

σm

102 103 104 105 106 107 108

, Nf

, σa (

MP

a)

CRACK LENGTH, a (μm)

10

100

STR

ESS

RAN

GE,

Δσ

(MPa

)

ΔKTH/(πa)0.5

ΔKTH/(π(a+a0))0.5

0.1 1 10 102 103 104 105

no fatigue failure

fatigue failureΔσfat

h

M

b

a

da/dN = 6.24 x 10-11 (ΔK)8.76

5 6 7 8 9 2 3 4 51STRESS-INTENSITY RANGE, ΔK (MPa√m)

10-8

10-7

10-6

10-5

10-4

CR

ACK-

GR

OW

TH R

ATE,

da/

dN (m

m/c

ycle

)

10-9

10-8

10-7

10-6

da/d

N (i

n/cy

cle)

5 6 7 8 9 2 3 41ΔK (ksi√in)

HUMAN DENTINR = 0.125°C, Hank's BSS

2TH0

fat

1( )σ

KaY πΔ

=Δ

“immortal”

“mortal”

Effect of Aging on Dentin Effect of Aging on Dentin -- TransparencyTransparency

Porter, Porter, NallaNalla, Minor, , Minor, JinschekJinschek, , KisielowskiKisielowski, , RadmilovicRadmilovic, Kinney, , Kinney, TomsiaTomsia & Ritchie, & Ritchie, BiomaterialsBiomaterials, 2005, 2005

10 μm10 μm 10 μm10 μm

Young (normal) Old (transparent)

AtomicAtomic--Force MicroscopyForce Microscopy

FIB & Transmission FIB & Transmission Electron MicroscopyElectron Microscopy

•• reconstructed exitreconstructed exit--wave lattice images wave lattice images imagesimages of of intratubularintratubularmineral in transparent dentin showing evidence of nanometermineral in transparent dentin showing evidence of nanometer--sized sized singlesingle--crystal apatite grains (crystal apatite grains (& Mg& Mg--rich rich ββ--tricalciumtricalcium phosphatephosphate))

•• aging leads to an altered form of dentin aging leads to an altered form of dentin ––transparent dentintransparent dentin

•• mineral concentration increases and distribution mineral concentration increases and distribution changes, due to filling up of tubules with mineralchanges, due to filling up of tubules with mineral

•• concentration differences due to crystallite size being concentration differences due to crystallite size being slightly smaller in transparent dentinslightly smaller in transparent dentin

•• collagen environment is changed in terms of collagen environment is changed in terms of intrafibrillarintrafibrillar mineral & overall density of fibrilsmineral & overall density of fibrils

P P

Healthy Root Transparent Root

concentration XX--ray Computed ray Computed TomographyTomographyof mineral

UV Raman SpectroscopyUV Raman Spectroscopy

Effect of Aging in Dentin: Property ChangesEffect of Aging in Dentin: Property Changes

•• YoungYoung’’s and shear modulus s and shear modulus unchanged with transparencyunchanged with transparency

•• normal dentin normal dentin ““yieldsyields””, with , with extensive postextensive post--yield deformationyield deformation

•• transparent (old) dentin is brittle transparent (old) dentin is brittle --no yieldingno yielding

•• fracture toughness is ~20% lower fracture toughness is ~20% lower in transparent dentinin transparent dentin

•• fatigue resistance generally lower fatigue resistance generally lower in transparent dentinin transparent dentin

Kinney, Kinney, NallaNalla, , PoplePople, , BreunigBreunig & Ritchie, & Ritchie, BiomaterialsBiomaterials, 2005, 2005

Resonance Ultrasound SpectroscopyResonance Ultrasound Spectroscopy

Elastic Elastic modulimoduli

0

0.5

1

1.5

2

FRA

CTU

RE

TO

UG

HN

ES

S (M

Pa√

m)

NORMAL TRANSPARENT

aver

age

age

80 y

rs

aver

age

age

24 y

rs

Fracture toughnessFracture toughness

UniaxialUniaxial stressstress--strain behaviorstrain behavior

0 0.2 0.4 0.6 0.8 1 1.2LOAD-LINE DISPLACEMENT (mm)

0

1

2

3

4

5

6

LOAD

(N)

HUMAN DENTIN25OC, HBSS

NormalTransparent

young

old

NO. OF CYCLES, Nf

0102030405060708090

100110120

STR

ES

S A

MP

LITU

DE

, σa (

MP

a) HUMAN DENTINR = 0.1, 10 Hz37OC, HBSS

NormalTransparent

102 103 104 105 106 107 108

FatigueFatiguetest samples

young

old

youn

g

youn

g

old

old

Effect of Aging on the Toughness of DentinEffect of Aging on the Toughness of Dentin

•• aging leads to reduced crack bridging, consistent with reductionaging leads to reduced crack bridging, consistent with reduction in fracture toughnessin fracture toughness•• filled tubules in aged dentin become less effective stressfilled tubules in aged dentin become less effective stress--concentratorsconcentrators

Kinney, Kinney, NallaNalla, , PoplePople, , BreunigBreunig & Ritchie, & Ritchie, BiomaterialsBiomaterials, 2005, 2005

old dentinold dentin

uncracked ligament bridges

tubules

filled-up tubules

young dentinyoung dentin

250 μm

500 μm

Young (normal)Young (normal)Old (transparent)Old (transparent)Soft XSoft X--Ray MicroscopyRay Microscopy

•• with aging, mineral concentration in dentin increases due to filwith aging, mineral concentration in dentin increases due to filling ling up of tubules with up of tubules with nanocrystallinenanocrystalline apatite (transparent dentin)apatite (transparent dentin)

•• postpost--yield stress/strain behavior eliminatedyield stress/strain behavior eliminated•• fracture toughness and fatigue resistance is reducedfracture toughness and fatigue resistance is reduced

Young (normal)

Old (transparent)

Environmental SEMEnvironmental SEM CX TomographyCX Tomography

Porter, Porter, NallaNalla, Minor, , Minor, RadmilovicRadmilovic, Kinney, , Kinney, TomsiaTomsia & Ritchie, & Ritchie, BiomaterialsBiomaterials, 2005;, 2005;

J.W. Ager

5 μm

J.W. Ager

crack path follows tubulescrack path follows tubules

Effect of Aging on Human BoneEffect of Aging on Human Bone

•• fracture toughness, and hence risk of fracture, of fracture toughness, and hence risk of fracture, of human bone severely degraded by agehuman bone severely degraded by age

•• significant deterioration in the collagensignificant deterioration in the collagen•• effect may be related to excessive remodeling with effect may be related to excessive remodeling with

age, which increases the age, which increases the osteonosteon densitydensity

0 2 4 6 8CRACK EXTENSION, Δa (mm)

0

2

4

6ST

RES

S IN

TEN

SITY

, K (M

Pa√m

)

34-41 yrs61-69 yrs

HUMAN CORTICAL BONEHBSS, 25oC

85-99 yrs

E = 780 MPa

E = 220 MPa

E = 780 MPa

E = 220 MPa

E = 1.22 GPa

37 yr old human bone collagen

picopico--force force AFMAFM--based based nanonano--indentationindentation

0.5 μm

1 μm

99 yr old human bone collagen

R-curves

Bone, Bone, Dec. 2004Dec. 2004

NallaNalla, , KruzicKruzic, Kinney & Ritchie, Bone 2004; , Kinney & Ritchie, Bone 2004; NallaNalla, , KruzicKruzic, , AgerAger, , BaloochBalooch, Kinney & Ritchie, , Kinney & Ritchie, Mat. Mat. SciSci. Eng. C. Eng. C, 2006, 2006

humeral cortical bonehumeral cortical bone

YoungYoung (34 yr) bone(34 yr) bone0.1 mm 0.5 mm 2.5 mm

500 μm

Deterioration in Human Bone from AgingDeterioration in Human Bone from Aging

Aged (85yr) bone

0.1 mm 0.5 mm 2.5 mm

NallaNalla, , KruzicKruzic, , AgerAger, , BaloochBalooch, Kinney & Ritchie, , Kinney & Ritchie, Mat. Mat. SciSci. Eng. C. Eng. C, 2006, 2006

0 5 10 15 20 25 30 35 40OSTEON DENSITY (/mm2)

0

0.5

1

1.5

2

2.5

3

INIT

IATI

ON

TO

UG

HN

ES

S, K

o (M

Pa√

m) HUMAN CORTICAL BONE

0 5 10 15 20 25 30 35 40OSTEON DENSITY (/mm2)

0

0.1

0.2

0.3

0.4

0.5

0.6

GR

OW

TH T

OU

GH

NES

S (M

Pa√m

/mm

) HUMAN CORTICAL BONE

•• size and area fraction of size and area fraction of crack bridges decrease crack bridges decrease with agewith age

•• possibly from excessive possibly from excessive remodeling remodeling →→ higher higher fraction of fraction of osteonsosteons

•• significant correlation of significant correlation of decrease in toughness with decrease in toughness with increase in increase in osteonosteon densitydensity

500 μm

Young (34 yrs)

Aged (85 yrs)

0 1 2 3 4 5 6DISTANCE FROM CRACK TIP (mm)

0

0.2

0.4

0.6

0.8

BR

IDG

ING

AR

EA

FR

AC

TIO

N

HUMAN CORTICAL BONEHBSS, 25OC

AgedAged (85 yr) bone(85 yr) bone

22--D D tomographstomographs show progressively show progressively fewer and smaller bridges in older bonefewer and smaller bridges in older bone

CXTCXT

NallaNalla, , KruzicKruzic, Kinney & Ritchie, , Kinney & Ritchie, BoneBone, 2004, 2004

crack bridges

osteons

Amide ICH2 wag

85 years

Amide III

69 years

34 years

1000 1200 1400 1600 1800WAVENUMBER (cm-1)

0

0.4

0.8

1.2

1.6

2

INTE

NS

ITY

(arb

. uni

ts)

Amide ICH2 wag

85 years

Amide III

69 years

34 years

1000 1200 1400 1600 1800WAVENUMBER (cm-1)

0

0.4

0.8

1.2

1.6

2

INTE

NS

ITY

(arb

. uni

ts)

DeepDeep--UV Raman SpectroscopyUV Raman Spectroscopy

500 μm

0.1 mm 0.5 mm 2.5 mm0.1 mm 0.5 mm 2.5 mm

Deterioration in Bone from SteroidsDeterioration in Bone from Steroids

•• GlucocorticoidsGlucocorticoids (GC)(GC) are steroid are steroid hormones widely used for hormones widely used for inflammatory diseases, such as inflammatory diseases, such as arthritis & dermatitisarthritis & dermatitis

•• clinical studies show clinical studies show increased risk increased risk of bone fracture (GCof bone fracture (GC--induced induced osteoporosis)osteoporosis)

•• GCs induce slower bone turnover GCs induce slower bone turnover by suppressing bone formationby suppressing bone formation

•• BisphosphonatesBisphosphonates, e.g., , e.g., RisedronateRisedronate (RIS),(RIS), are effective are effective therapies, inhibiting bone therapies, inhibiting bone resorptionresorptionand reducing fracture riskand reducing fracture risk

PLGC GC+RIS

150 μm

CXTCXT

GC PL GC+RIS

500 μm

GC+RISGC+RIS

5 μm

GCGC

M

BM

•• GCs lead to GCs lead to ““soft spotssoft spots”” -- halos of low stiffness halos of low stiffness hypohypo--mineralized bone around larger mineralized bone around larger osteocyteosteocytelacunae lacunae –– toughness (mouse femurs) reduced 20%toughness (mouse femurs) reduced 20%

•• concurrent RIS treatment suppress such concurrent RIS treatment suppress such ““soft soft spotsspots”” -- toughness is increased by 25%toughness is increased by 25%

(Nancy Lane, (Nancy Lane, UCDavisUCDavis))

Balooch, Yao, Balooch, Yao, AgerAger, , BaloochBalooch, , NallaNalla, Porter, , Porter, MastroianniMastroianni, Ritchie & Lane, , Ritchie & Lane, Arthritis & Rheumatism,Arthritis & Rheumatism, 20072007

mouse bone (tibias)

5th lumbar vertebral bodies

mCTmCT

AFMAFM

Effect of Effect of RaloxifeneRaloxifene, , RisedronateRisedronate and and ZoledronateZoledronate on Estrogenon Estrogen--Deficient BoneDeficient Bone

(a) (b)

(c)

•• study on study on rat femursrat femurs, , ovarectomizedovarectomized (OVX) at 18 (OVX) at 18 mtsmts

•• given given RaloxifeneRaloxifene (RAL) or (RAL) or bisphosphonatesbisphosphonates -- RisedronateRisedronate(RIS) or (RIS) or ZoledronateZoledronate (ZOL) (ZOL) --immediately afterwards, tested immediately afterwards, tested after 60 daysafter 60 days

•• RAL offsets estrogenRAL offsets estrogen--deficiency; deficiency; RIS & ZOL inhibit bone RIS & ZOL inhibit bone resorptionresorption

(Nancy Lane, (Nancy Lane, UCDavisUCDavis))

Yao, Yao, BaloochBalooch, Koester, Ritchie, Lane, Koester, Ritchie, Lane, et al. , et al. 20062006

SHAM OVX OVX+Ral OVX+Ris OVX+Zol0

1

2

3

4

5

FRA

CTU

RE

TO

UG

HN

ES

S (M

Pa√

m)

Sham & OVX+RALSham & OVX+RAL OVXOVX

OVX + RIS/ZOLOVX + RIS/ZOL•• compared to Sham, crack compared to Sham, crack

path, which has a radical path, which has a radical effect on toughness, effect on toughness, markedly different in RIS markedly different in RIS & ZOL treated bone& ZOL treated bone

•• crack paths are very crack paths are very tortuous in RIS & ZOLtortuous in RIS & ZOL--treated cortical bonetreated cortical bone

Loss in boneLoss in bone--matrix toughness due to matrix toughness due to ovarectomyovarectomymore than compensated by more than compensated by RaloxifeneRaloxifene, , RisedronateRisedronateor or ZoledronateZoledronate treatmentstreatments

Fracture Risk Assessment from BiopsiesFracture Risk Assessment from Biopsies

•• we can induce stable we can induce stable cracks in cortical bone cracks in cortical bone

•• crack path, crack path, c.f.,c.f., micromicro--structure, used to structure, used to assess toughening or assess toughening or deteriorationdeterioration

•• we believe that we can we believe that we can measure a measure a KKcc as a as a quantitative measure quantitative measure of bone quality for of bone quality for living patientsliving patients

Koester, Ritchie Koester, Ritchie et alet al.., , 20062006

•• microcrackingmicrocracking, at cement lines, promotes toughness via bridging, at cement lines, promotes toughness via bridging•• cracks often follow cracks often follow osteocyteosteocyte lacunae lacunae

iliac crest biopsiesiliac crest biopsies(supplied by (supplied by Juliet Juliet CompstonCompston ((CambCamb) via ) via Nancy LaneNancy Lane (UC Davis)(UC Davis)

Alcohol Strengthens Teeth Alcohol Strengthens Teeth –– at least temporarily!at least temporarily!

•• but you do need to keep the alcohol in your mouth, as the but you do need to keep the alcohol in your mouth, as the effect is reversible!effect is reversible!

•• effect associated with direct collageneffect associated with direct collagen--collagen Hcollagen H--bonding bonding in polar solvantsin polar solvants

NallaNalla, Kinney, , Kinney, TomsiaTomsia & Ritchie, & Ritchie, Journal of Dental ResearchJournal of Dental Research, 2006, 2006

0 2 4 6CRACK EXTENSION, Δa (mm)

0

1

2

3

4

5

STR

ESS

INTE

NSI

TY, K

(MPa

√m)

ELEPHANT DENTINWHISKEY, 25oC

initiation toughness

growth toughness

plateau toughness

HBSS

Ethanol

0 2 4 6 8 10CRACK EXTENSION, Δa (mm)

0

1

2

3

4

5

STR

ESS

INTE

NSI

TY, K

(MPa

√m)

dehydrated with whiskey

dehydrated with whiskey

re-hydrated with HBSS

8686--proof Black & White scotch whiskeyproof Black & White scotch whiskey

•• compared to water compared to water (HBSS), whiskey (HBSS), whiskey increases the increases the stiffness, strength stiffness, strength & toughness of & toughness of dentindentin

hydrated collagen (40 MPa)

acetone (1.2 GPa)

rehydrated collagen (30 MPa)

0 100 200 300 400 500DEPTH (nm)

0

20

40

60

80

100

LOAD

(μΝ

)

1 μm 0.1 μm

AFM-based pico-indentation

collagen stiffness

R-curves

tensile tests

R-curves

NallaNalla, , BaloochBalooch, , AgerAger, , KruzicKruzic, Kinney & Ritchie, , Kinney & Ritchie, ActaActa BiomaterialiaBiomaterialia, 2005, 2005

Bone Quality: Transforming Growth FactorsBone Quality: Transforming Growth Factors

•• TGFTGF--ββ is a family of proteins (cytokine) is a family of proteins (cytokine) that can regulate behavior in bone that can regulate behavior in bone

•• TGFTGF--ββ can inhibit can inhibit osteoblastosteoblast formation formation --osteoclastsosteoclasts are unaffectedare unaffected

•• too much TGFtoo much TGF--ββ (over(over--expression) expression) leads to (27%) lower bone toughness leads to (27%) lower bone toughness (and osteoporosis) (and osteoporosis)

•• underunder--expressing TGFexpressing TGF--ββ leads to leads to increased bone deposition, enhanced increased bone deposition, enhanced mineral content, mineral content, 50% higher bone 50% higher bone toughness and more tortuous crack pathstoughness and more tortuous crack paths

Role of TGFRole of TGF--ββ on mouse boneon mouse bone

over

-exp

Balooch, Balooch, BaloochBalooch, , NallaNalla, Schilling, , Schilling, FilvaroffFilvaroff, Marshall, Marshall, Ritchie, , Marshall, Marshall, Ritchie, DerynckDerynck & & AllistonAlliston, , PNASPNAS, Dec. 2005, Dec. 2005

0.00

1.00

2.00

3.00

4.00

5.00

Fra

ctu

re T

ou

gh

ness

(M

Pam

-1/

2)

D4

D5

WT

E1

Smad3 +/-

Smad3 -/-

wild

-type

over

-exp

over

-exp

unde

r-exp

(rec

epto

r)

unde

r-exp

(par

tial k

-o)

k-o

Fracture ToughnessFracture Toughness

S = 5.5 mm

500 μm

50 μm 500 nm

500 μm 50 μm 500 nm

poor minerali-zation

unde

r-ex

pres

sed

o

ver-

expr

esse

d

Mouse bone and TGF-β

possible new possible new therapy to treat therapy to treat bone disorders?bone disorders?

SEMSEMCXTCXT

((RikRik DerynckDerynck, UCSF), UCSF)

mouse mouse femursfemurs

•• One measure of One measure of bone qualitybone quality is the fracture toughness. This requires an is the fracture toughness. This requires an understanding of fracture mechanisms and how they are affected bunderstanding of fracture mechanisms and how they are affected by microstructurey microstructure

•• Whereas fracture Whereas fracture initiationinitiation in bone is strainin bone is strain--controlled, (crackcontrolled, (crack--growth) toughness is growth) toughness is derived from derived from extrinsicextrinsic toughening mechanisms, which promote Rtoughening mechanisms, which promote R--curve behaviorcurve behavior

•• For crack For crack propagationpropagation, the salient extrinsic toughening mechanisms are:, the salient extrinsic toughening mechanisms are:•• crack bridging by crack bridging by uncrackeduncracked ““ligamentsligaments”” (and by individual collagen fibrils)(and by individual collagen fibrils)•• crack deflection along cement lines (transverse orientation)crack deflection along cement lines (transverse orientation)

•• Although mechanisms are controlled by the hierarchy of structureAlthough mechanisms are controlled by the hierarchy of structure, features at , features at coarse lengthcoarse length--scales, ~100scales, ~100--200 200 μμm, are most important for fracture toughnessm, are most important for fracture toughness

•• Aging of dentin and bone identified with a loss in toughness, asAging of dentin and bone identified with a loss in toughness, associated in part with sociated in part with a deterioration in crack bridging (consistent in bone with excesa deterioration in crack bridging (consistent in bone with excessive remodeling)sive remodeling)

•• Regulation of growth factors (e.g., TGFRegulation of growth factors (e.g., TGF--ββ) can have a significant and positive effect ) can have a significant and positive effect on the mechanical properties of bone on the mechanical properties of bone -- at at nanonano to macro lengthto macro length--scales scales

•• Whereas Whereas ovarectomiesovarectomies & steroids can prematurely degrade fracture toughness, & steroids can prematurely degrade fracture toughness, RaloxifeneRaloxifene or or bisphosphonatebisphosphonate treatments act to restore, or even enhance, fracture treatments act to restore, or even enhance, fracture resistance resistance -- mechanically due to microstructuremechanically due to microstructure--induced changes in crack pathinduced changes in crack path

ConclusionsConclusions

PersonnelPersonnel

• UCB: Ravi Nalla (Intel), Kurt KoesterValentina Imbeni (SRI) Jay Kruzic (Oregon State)

• LBNL: Joel Ager, Alex Porter (Camb.) Eduardo Saiz, Tony Tomsia

• LLNL: John Kinney, James Stölken

• UCSF: Guive Balooch, Medhi BaloochRik DerynckBill & Sally Marshall

• UC Davis: Nancy Lane, Wei Yao,Dave Fyhrie

• Rockwell: Brian Cox

AcknowledgmentsAcknowledgments

FundingFunding• Dept. of Energy – BES• LBNL – LDRD• NIH – Bioengineering

Research Partnership• NIH - Dental & Craniofacial

Research FacilitiesFacilities•• Advanced Light Source Advanced Light Source

(LBNL)(LBNL)•• Stanford Synchrotron Stanford Synchrotron

Radiation Lab. (SSRL)Radiation Lab. (SSRL)•• National Center for Electron National Center for Electron

Microscopy (LLBL) Microscopy (LLBL)

Web pageWeb page•• www.LBL.govwww.LBL.gov/Ritchie/Ritchie