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Self-Aligning Monomers forLow Shrinkage, Biomedical

Composites

H. Ralph RawlsB. K. Norling, QIAN Wang, Nga M. Tang, P. Longo

University of TexasUniversity of Texas

Health Science Center at San AntonioHealth Science Center at San Antonioandand

S.T. Wellinghoff,B.F. Furman & D.P. NicolellaSouthwest Research Institute, San Antonio, TexasSouthwest Research Institute, San Antonio, Texas

Composites at Lake Louise, OctoberComposites at Lake Louise, October20092009

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UTHSCSA Biomaterials 2

Problems withProblems withDental CompositesDental Composites

PulpPulpPulpPulp

SecondaryCariesSecondaryCaries

Pulp

Infection

Pulp

Infection

Wear,

fracture,

Leakage,

Staining

Wear,

fracture,

Leakage,

Staining

PulpPulpPulpPulp

Composite

ADRS project NIH supported

UTHSCSA & SwRI

Radiopaque

Nano Fillers

Radiopaque

Nano Fillers

Solutions we are developing:Ultra-small,nanometer-sized fillers toreduce wear & impart high translucency

Metal oxide fillers for radiopacity

Liquid-

Crystal

Monomer

Liquid-

Crystal

Monomer

Liquid crystal monomers toreduce cure shrinkage and

viscosity

SolutionsSolutions

Color InstabilityColor InstabilityCure ShrinkageCure Shrinkage

Major problems:Cure shrinkage, wear, fracture &thermal expansion/contraction result inmarginal break-down

This is followed by leakage,staining,secondary caries and, in the worst

cases, pulp exposure and infection.Initial color and color instability

Low Color,synergizing

photo-sensitizers

Low Color,synergizing

photo-sensitizers

Low Color, color stable initiatorsLow Color, color stable initiators

Low Color, color stable initiatorsLow Color, color stable initiators

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Low Polymerization-Contraction

via Liquid CrystalMonomers

Strategy for reducing cure

shrinkage in biomedical

and engineering resins

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UTHSCSA Biomaterials 4

Molecular Organization in

Isotropic and Nematic Liquids

Isotropic

random

Isotropic

random

Nematic

Self-aligned

Nematic

Self-aligned

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UTHSCSA Biomaterials 5

Liquid and Nematic-Liquid-Crystal Structures

Ordinary, Isotropic, LiquidMonomers are randomly

alignedwith no order

Nematic Liquid-CrystalMonomers are aligned in one

dimension

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UTHSCSA Biomaterials 6

Liquid Crystal Dimethacrylate

Monomers Have Rod-Like Structures

OO

OO

OO

O

O

R

R = H, CH3n=1,5 n=1,5

O OR

n = 1n = 1 3-t-butyl 1,4-di(4-3-t-butyl 1,4-di(4-[meth][meth]acryloxy-hexaneoxy) benzoyloxy)-acryloxy-hexaneoxy) benzoyloxy)-

benzenebenzene

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UTHSCSA Biomaterials 7

C6-t-butyl-dimethacrylate MW = 743

Bis-GMAMW = 513

TEGDMA MW = 258

Molecular Weight is Higherbut Viscosity is Much Less

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Nematic Liquid-Crystal Synthesis+1)

100% NO2OO (CH2)6 OC

O

C

O

NO2

2) + DMSO O C

O

O +

C

O

O>90%

NO2C

O

NO2 OH+ O(CH2)6C

OTi(O Bu)4HO(CH2)6OH OH

HO(CH2)6 OC

O

(CH2)6OHHO(CH2)

O(CH2)6

K+ - O(CH2)6OH

OHO(CH2)6

3)a) NaOH

b) HClO C

O

OH100%

4)Cl (CH2)6 O C

O

Cl 90%

5) + HO OH

C4H9

C

O

O OC

O

>90%

N

HO(CH2)6

O(CH2)6Cl

LC at RT

Cl(CH2)6O

SOCl2

6)H2O

HMPANMP

HO(CH2)6 O C

O

O OC

O

O(CH2

)6

OH(KBr)

+

CH 2=CCO(CH 2)6O

CH 3

O

C

O

O OC

O

O(CH2)6OH OCC=CH 2

CH 3

O

7)

90% LC at RT

CH 2=CCCl

CH 3

O CH 2=CCO(CH 2)6O

CH 3

O

C

O

O OC

O

O(CH2)6OH

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UTHSCSA Biomaterials 9

Polarized Light Microscopy

of LC MonomersOriented Nematic

25o C

Isotropic State

45o C

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UTHSCSA Biomaterials 10

a or me ry:n i TransitionTemperatureIsotropic State

> 46o C

Oriented Nematic

< 43o C

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UTHSCSA Biomaterials 11

PolymerizationShrinkage vs.Time

0

1

2

3

4

5

6

7

8

910

0 0.2 0.4 0.6 0.8 1

Time (min)

Experimental C6-LC diacrylate resin

UnfilledBis-GMA based resin

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UTHSCSA Biomaterials 12

Mechanism of Low ShrinkageMechanism of Low Shrinkagein Liquid Crystal Monomersin Liquid Crystal Monomers

When LC monomer is converted topolymer, the alignment among molecules

is disrupted and causes a small expansion

LC Composites are pre-aligned andhighly compact.

Thus very little shrinkage occurs whenmonomer is converted to polymer

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UTHSCSA Biomaterials 13

0

4

8

12

16

Commercial

Resin

LC6diacr-

Unfilled

Ivoclar-

Tetric

Vivadent's

Heliomolar-s

LC6diacr-

Tetric

M o d u l u s ( G P a )

unfille Composite

Liq CrLiqCrys

HybriMicFill

BisGbase

p < 0.05

*

*

**

Modulus (rigidity) too Low

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UTHSCSA Biomaterials 14

0

40

80

120

160

Commercial

Resin

LC6diacr-

Unfilled

Ivoclar-Tetric Vivadent's

Heliomolar-s

LC6diacr-

Tetric

F l e x u r a l S t r e n g t h (M P a )

unfille Composite

Liq

Cr

Liq

Cr Hybr

MicrFill

BisGbase

*

*

**

p < 0.05

Strength too Low

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0

20

40

60

80

100

120

GTE

10%

IBM

w/GTE

20%

IBM

w/GTE

10%

TMPT

MAw/

GT

E

20%

TMPT

MAw/

GTE

LCM

10%

IBM

w/LCM

20%

IBM

w/LCM

10%

TMPT

MAw/

LCM

Flexure

Strength

(MPa)

0

20

40

60

80

100

120

GTE LCM

10%

IBM

20%

IBM

10%

TMPT

MA

20%

TMPT

MA

FlexureStreng

th(MPa)

Bis-GMA Resin Liquid Crystal Resins

Add Other Monomers:Flexure Strength Increases

IBM = iso-bornylmethacrylateIBM = iso-bornylmethacrylate

LC + IBMLC + IBMGTEGTE LCLCLC +

TMPTMALC +

TMPTMA

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UTHSCSA Biomaterials 16

Modulus (rigidity) Increases

0

500

10001500

2000

2500

3000

LCM

Mod

ulus(M

Pa)

0

500

1000

1500

2000

2500

3000

GTE LCMLCM

10%

IBM

20%

IBM

10%

TMPT

MA

20%

TMPT

MA

Modu

lus(M

Pa)

Bis-GMA Liquid Crystal Resins

LC + IBMLC + IBMGTEGTE LCLCLC +

TMPTMALC +

TMPTMA

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UTHSCSA Biomaterials 17

Bis-GMA based 8 vol%

Liquid-Crystal 2 vol%Liq-Cryst + IBM 2 vol%

Cure Shrinkage

Remains Low

BUT

Cure Rate is TooSlow!!

BUT

Cure Rate is TooSlow!!

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UTHSCSA Biomaterials 18

LCMCure Ratei

Slow

0%

10%

20%

30%

40%

50%

60%

70%

0 50 100 150 200 250 300

Exposure Time (seconds)

Bis GMA-basedBis GMA-based

Liq. CrystalLiq. Crystal

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UTHSCSA Biomaterials 19

0 %

1 0 %

2 0 %

3 0 %

4 0 %

5 0 %

6 0 %

7 0 %

0 5 0 1 0 01 5 02 0 02 5 03

E x p o s u r

Bis-GMA basedBis-GMA based

Liq. CrystalLiq. Crystal

Longer exposure times are required for LiquidLonger exposure times are required for LiquidCrystals to reach the same degree of cure asCrystals to reach the same degree of cure as

GTEGTE

Longer exposure times are required for LiquidLonger exposure times are required for LiquidCrystals to reach the same degree of cure asCrystals to reach the same degree of cure as

GTEGTE

20

min

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Curing Systems &Setting Mechanisms

Strategy for fast cure, lowcolor, color stable resins

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UTHSCSA Biomaterials 21

Photoiniator SystemPhotoiniator System

CQQ Camphor-Quinone

CQCQabsorbs BLUEBLUElight and photosensitizesDMAEMADMAEMA to form free radicals and initiatepolymerization

DMAEMAMAEMAN,N-Dimethyl-AminoEthyl

Methacrylate

+

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UTHSCSA Biomaterials 22

Onium-ion Photoinitiator:OPPIOPPI

p-octyloxy-phenyl-phenyliodonium hexafuoro antimonate

I+

OPPI accelerates both LCM c re

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UTHSCSA Biomaterials 23

0%

10%

20%

30%

40%

50%

60%

70%

0 50 100 150 200 250 300

Exposure Time (seconds

Liq CrystalLiq Crystal

Liq Crystal + OPPIOPPILiq Crystal +OPPIOPPI

Bis-GMA basedBis-GMA based

+ . . . it Reduces YellowColor+ . . . it Reduces YellowColor

OPPI accelerates both LCM curerate & Deg. of Conversion

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UTHSCSA Biomaterials 24

Single LC Monomer

Shortcomings

Crystallize in the present of fillers

Inadequate tsn - tn i range:

Shrinkage increases as t approaches

the n i transformation temperature,

~45C

Mouth temp. shrinkage > RT shrinkage

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Blended Liquid

Crystal MonomerSystems

SHELF-LIFE:Strategy to prevent Liquid

Crystals from crystallizing in the

presence of reinforcing fillers

S l ti LC M

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UTHSCSA Biomaterials 26

Solution: LC-Monomer

Blends

Blends prevent 3-dimensional ordernucleated by inorganic fillers

long-term stability against crystallization

Co-synthesize a mixture of related

monomers in a single pot

S b l d Adi l

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UTHSCSA Biomaterials 27

Sebacyl and Adipyl

t-butyl

O

O

O

CH3

O

O

O O

O

O

O

O

O

O

O

O H

O

CH3

H

H

H

MW = 943

16 component Liquid

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UTHSCSA Biomaterials 28

O

R2,1

O

O

O

R3,2

R3,1

CH2

O

R4 O

O

O

O

O

O

O

R2,2R1

O

O

O

R3,1

R3,2

CH2

O

R4

n

R4-CH

3; R

3,2R

3,1-H; R

2,2-(CH

2)

4or (CH

2)

8; R

1-tC

4H

9or CH

3

A2 S2 MA2 TA2 MAS TAS MS2 TS2 N > 2

RT min 3.16 3.94 5.92 8.52 13.39 21.14 33.10 55.21 MR

Mole % 1.2 0.8 8.4 6.5 22.8 17.9 17.3 12.3 12.8

bis (oxyethyl methacrylate)bis (oxyethyl methacrylate) adipoateadipoate, A, A22

andand sebacoatesebacoate, S, S22

TT andand MM represent Rrepresent R11-tC-tC44HH99 , CH, CH33 ,,AA andand SS represent Rrepresent R

2,22,2-(CH-(CH

22))44

and (CHand (CH22))88

Q u i c k T i m e a n d ad e c o m p r e s s o r

a r e n e e d e d t o s e e t h i s p i c t u r e .

16-component LiquidCrystal Monomer Blend

M t i l d th d

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UTHSCSA Biomaterials 29

Materials and methods

16-component blend was initiated with 1% CQand 2% DMAEMA.

75% 1 micron Ba-Glass filler, stored refrigerated. A control mixture ofBisGMA 37.5% -TEGDMA

37.5% and BisEMA 25% was used forcomparison.

Degree of conversion and initial cure rate weremeasured by FTIR

Volumetric shrinkage was measured in an Acuvol Transverse strength and moduli were measured

on 2 mm square beams in an Instron/MTS

C C t ti

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UTHSCSA Biomaterials 30

Cure Contraction

C Ch t i ti

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UTHSCSA Biomaterials 31

Cure Characteristics

P=0.001

P=0.022

Mechanical

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UTHSCSA Biomaterials 32

0

10

20

30

40

50

60

70

80

90

0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16

Stress (MPa)

Strain (mm/mm)

O

F

Y

B

M

Mechanical

Properties

SAMT exhibits a high

degree of shear

yielding even at high

crosslink density andcure

SAMT exhibits a high

degree of shear

yielding even at high

crosslink density andcure

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UTHSCSA Biomaterials 33

Microtomed Photopolymerized SAMT Blend

& SAMT Composite (Crossed Polarizers)

LC state is maintained in the polymerized material

SAMT SAMT COMPOSITE

500x Magnification

10 m

500x Magnification

10 m10 m

500x Magnification

10 m

500x Magnification

10 m10 m

Small Angle X-ray Diffraction of SAMT

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UTHSCSA Biomaterials 34

L=5.65nmOverlay

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

2 theta

lc data

sc

sb

SD

SG

Before Polymerization

After Photopolymerizaton

4.4 nm

L=4.58nm

Courtesy: S. Swinnea, UT Austin

Small Angle X-ray Diffraction of SAMT

Monomer blend and Polymer

Smectic

Liquid Crystal

Smectic

Liquid Crystal

R lt

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UTHSCSA Biomaterials 35

ResultsSAMT liquid crystal monomer blend:

Composite does not crystallizeStable > 3 years Refrigerated In presence of high filler loadingShrinkage reduced by ~75% Mechanical properties ~ current resins Cure rate ~ current dental resins Blend is smectic rather than nematic Smectic phases remain after curing Light scattering --> low translucency

Bi tibilitBi tibilit

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UTHSCSA Biomaterials 36

BiocompatibilityBiocompatibility

StudiesStudiesLC-blend monomers and polymers

less cytotoxic than commercial

resins

LC-blend restorative compositeutilized in ferret animal model withno adverse effects

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UTHSCSA Biomaterials 37

Synthesis simplification and scale-up. Eliminate smectic and phases in the

polymerized composite.

Reduce light scattering to improve estheticproperties

Optimize particulate-filled formulations Nanoparticle reinforcing fillers

Characterize wear resistance

Clinical trials

In Progress and Future Studies

A k l d t

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UTHSCSA Biomaterials 38

AcknowledgementsSSupported byupported by::NIH / NIDCRNIH / NIDCR

Grant numbersGrant numbers

P01 DE11688P01 DE11688

R01 DE06179R01 DE06179

EssTech & UltradentEssTech & Ultradent

(Monomers)(Monomers)

Kerr, Schott Glas (fillers)Kerr, Schott Glas (fillers)

UTHSCSA & SwRIUTHSCSA & SwRIinternal fundsinternal funds

University of Texas HSCUniversity of Texas HSC

BK Norling,BK Norling, K Whang,K Whang, Neera Satsangi,Neera Satsangi,

V Lee,V Lee,HL Cardenas, Q WhangHL Cardenas, Q Whang

Southwest Research InstituteSouthwest Research Institute

ST Wellinghoff, D Nicolella, H Dixon, D Hanson,ST Wellinghoff, D Nicolella, H Dixon, D Hanson,J McDonough, BR Furman, P ThompsonJ McDonough, BR Furman, P Thompson

Universities in, South KoreaUniversities in, South KoreaY-J Park, D. ShenY-J Park, D. Shen

StudentsStudents

Dental School, Co*Star, TAMU, UTSA, UW atDental School, Co*Star, TAMU, UTSA, UW atSt. Louis, UTHSCSA-Biomedical Engineering,St. Louis, UTHSCSA-Biomedical Engineering,

Health Careers and Clark High Schools, andandothersothers TNTMTNTM

University of Texas HSCUniversity of Texas HSC

BK Norling,BK Norling,

K Whang,K Whang,

Neera Satsangi,Neera Satsangi,

V Lee,V Lee,

HL Cardenas, Q WhangHL Cardenas, Q Whang

Southwest Research InstituteSouthwest Research Institute

ST Wellinghoff, D Nicolella, H Dixon, D Hanson,ST Wellinghoff, D Nicolella, H Dixon, D Hanson,J McDonough, BR Furman, P ThompsonJ McDonough, BR Furman, P Thompson

Universities in, South KoreaUniversities in, South Korea

Y-J Park, D. ShenY-J Park, D. Shen

StudentsStudents

Dental School, Co*Star, TAMU, UTSA, UW atDental School, Co*Star, TAMU, UTSA, UW atSt. Louis, UTHSCSA-Biomedical Engineering,St. Louis, UTHSCSA-Biomedical Engineering,Health Careers and Clark High Schools, andandothersothers TNTMTNTM

Advanced Dental Restorative SystemsAdvanced Dental Restorative Systems

NIDCR grantNIDCR grantP01 DE11688P01 DE11688

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QUESTIONS ?

H H

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UTHSCSA Biomaterials 40

FTIR - Degree of Conversion DC:

Measured by

changes in

aliphaticpeak

vs.

aromaticpeak

1637 cm1637 cm-1-1 :aliphaticdouble bonds

decrease

1608 cm-1 :aromaticaromatic,internalstandard,remains

unchangedDeg. Conversion

=

1-(h2/h1)*(H1/H2) x

100

h

H

RO

OO

O

OR

O

OO

O

O

H H

S

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UTHSCSA Biomaterials 41

Volumetric Shrinkage

This instrument uses image

recognition by pixel contrast to

outline the specimen and calculate

the volume before and after

polymerization (Martin, 2001).

Acuvol Bisco Inc.Acuvol Bisco Inc.

Transverse Strength &

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Transverse Strength &

Modulus