Composites at Lake Louise, October

2009

Self-Aligning Monomers for

Low Shrinkage, Biomedical
Composites
H. Ralph Rawls
B. K. Norling, QIAN Wang, Nga M. Tang, P. Longo
University of Texas
Health Science Center at San Antonio
and
S.T. Wellinghoff, B.F. Furman & D.P. Nicolella
Southwest Research Institute, San Antonio, Texas
 Problems with Solutions
Dental Composites
Cure Shrinkage
Color Instability
Radiopaque
Wear, Nano Fillers
fracture,
Leakage, Liquid-
Staining Crystal
Composite Monomer
Secondary
Caries
Low Color,
Pulp
Pulp Pulp synergizing
photo-
Pulp
sensitizers
Infection
Major problems: Solutions we are developing:
Cure shrinkage, wear, fracture & Ultra-small,“nanometer-sized fillers to
thermal expansion/contraction result in reduce wear & impart high translucency
marginal break-down
 Metal oxide fillers for radiopacity
 This is followed by leakage,staining,  • crystal
LiquidADRS project
monomers to
secondary caries and, in the worst • NIH
reduce cure shrinkage and
supported
cases, pulp exposure and infection. viscosity
• UTHSCSA & SwRI
 UTHSCSA Biomaterials
Initial color and color instability Low
Low Color,
Color, color
color stable
stable initiators
initiators 2
Low Polymerization-
Contraction
via Liquid Crystal
Monomers
Strategy for reducing cure
shrinkage in biomedical
and engineering resins
 Molecular Organization in
Isotropic and Nematic Liquids

Isotropic Nematic
random Self-aligned
UTHSCSA Biomaterials 4
 Liquid and Nematic-Liquid-
Crystal Structures

Ordinary, “Isotropic,” Liquid Nematic Liquid-Crystal

Monomers are randomly Monomers are aligned in one
aligned with no order dimension
UTHSCSA Biomaterials 5
 Liquid Crystal Dimethacrylate
Monomers Have Rod-Like Structures

O O
R O O R
O O
n=1,5 O O n=1,5 O
O
R = H, CH3
• n=1
• 3-t-butyl 1,4-di(4-[meth]acryloxy-hexaneoxy) benzoyloxy)-
benzene

UTHSCSA Biomaterials 6
 Molecular Weight is Higher
but Viscosity is Much Less

TEGDMA MW = 258

Bis-GMA
MW = 513

C6-t-butyl-dimethacrylate MW = 743

UTHSCSA Biomaterials 7
Nematic Liquid-Crystal Synthesis
O O
Ti(O Bu)4
1) HO(CH2)6OH + NO2 C OH NO2 C O(CH2)6OH +

O O
100% NO2 C O (CH2)6 OC O NO2

O
2) + K+ - O(CH2)6OH DMSO HO(CH2) O C O(CH2)6OH +
O O
HO(CH2)6 O C O(CH2)6 OC O(CH2)6 OH
>90%
a) NaOH
3) O
b) HCl 100%
HO(CH2)6 O C OH

O
4) SOCl2
Cl (CH2)6 O 90%
C Cl

C4H9 N
O O
5) + HO OH Cl(CH2)6O C O OC O(CH2)6Cl

>90% LC at RT
O O
H2O (KBr)
6) HO(CH2)6 O C O OC O(CH2)6OH
HMPA
NMP

90% LC at RT

CH3

7) CH2=C—C—Cl O O O
O CH2=C—CO(CH2)6O C O OC O(CH2)6OH
CH3
+
O O O CH3
CH2=C—CO(CH2)6O C O OC O(CH2)6OH —O—C—C=CH2
CH3 O
Polarized Light Microscopy
of LC Monomers
Oriented Nematic Isotropic State
25o C 45o C

UTHSCSA Biomaterials 9
 DSC / Calorimetry:
n→i Transition Temperature
Isotropic State
> 46o C

Oriented Nematic
< 43o C

UTHSCSA Biomaterials 10
 Polymerization
Shrinkage vs. Time
Unfilled Bis-GMA based resin

Experimental C6-LC diacrylate resin

UTHSCSA Biomaterials 11
 Mechanism of Low Shrinkage
in Liquid Crystal Monomers

• LC Composites are “pre”-aligned and

highly compact.
• Thus very little shrinkage occurs when
monomer is converted to polymer

• When LC monomer is converted to

polymer, the alignment among molecules
is disrupted and causes a small expansion

UTHSCSA Biomaterials 12
Modulus (rigidity) too Low
16

unfilled Composites
12
p < 0.05
*
8 Hybride
BisGMA
based Liq Micro Liq Cryst
Cryst Fill
Modulus (GPa)
4
**
*
0

Commercial LC6diacr- Ivoclar- Vivadent's LC6diacr-

Resin Unfilled Tetric Heliomolar-s Tetric

UTHSCSA Biomaterials 13
 Strength too Low
160
unfilled Composites
*
120
p < 0.05
BisGMA
based
80 Liq *
Cryst Hybrid
e
40 Micro **
Flexural Strength (MPa) Fill Liq
Cryst
0
Commercial LC6diacr- Ivoclar-Tetric Vivadent's LC6diacr-
Resin
UTHSCSA Biomaterials Unfilled Heliomolar-s Tetric 14
 Flexure Strength (MPa)
•Flexure Strength (MPa)

20
40
60
80
100
120

0•0
•2•0
•4•0
•6•0
•8•0
•1•0•0
•1•2•0
•1
0% •G
TE
IB
M
•2 w
0% G/ G
TT
•1 EE
IB GTE
M
0% GTE
TM w
/G
• P T
•2 10 TM •L E
0% % A LCC
I M
M
TM B1M w/ G
LC
LC

•2 PT 0%w/ TE
0% M IBLC
A
•1 IB w MM
0% 2M /
LC

0%w GT
TM
LC +

/L E
IB C
10PTM MM
% A
+ IBM
IBM

TMw
PT/ LC
MM
20
% A
TM
LC

PT
LC +

M
+

A
TMPTMA
Bis-GMA Resin Liquid Crystal Resins

TMPTMA
Add Other Monomers:

IBM = iso-bornylmethacrylate
Flexure Strength Increases
Modulus (rigidity) Increases
Bis-GMA Liquid Crystal Resins
3000
•3•0•0•0
LC
LC +
+
(MPa)
•Modulus(MPa)

2500 GTE
GTE LC
LC LC
LC +
+ IBM
IBM TMPTMA
TMPTMA
•2•5•0•0
2000
•2•0•0•0
Modulus

1500
•1•5•0•0
1000
•1•0•0•0
500
•5•0•0
0•0
E

M
20 M

A
M

A
T

CM

IB

M
IB

M
G

LC

PT
%

T
•L

TM
10

M
T

%
%

20
10

UTHSCSA Biomaterials 16
 Cure Shrinkage
Remains Low
Bis-GMA based 8 vol%
Liquid-Crystal 2 vol%
Liq-Cryst + IBM 2 vol%
BUT
Cure Rate is Too
Slow!!
UTHSCSA Biomaterials 17
 LCM
Cure Rateis
70%
Slow
60% Bis GMA-based
50%
Liq. Crystal
40%

30%
(% DC)
20%

10% of Conversion
Degree
0%
0 50 100 150 200 250 300
Exposure Time (seconds)
UTHSCSA Biomaterials 18
Longer exposure times are required for Liquid Crystals
to reach the same degree of cure as GTE
70%

60% Bis-GMA based

50%
Liq. Crystal
40%

30%
DC %
20%

10%

0%
0 50 100 150 200 250 300 20
Exposure Time (seconds)
min
UTHSCSA Biomaterials 19
 Curing Systems &
Setting Mechanisms
Strategy for fast cure, low
color, color stable resins
 Photoiniator System
CQ DMAEMA
Camphor- N,N-Dimethyl-
Quinone AminoEthyl
Methacrylate

+
CQ absorbs BLUE light and photosensitizes
DMAEMA to form free radicals and initiate
polymerization

UTHSCSA Biomaterials 21
Onium-ion Photoinitiator: OPPI

I+

p-octyloxy-phenyl-phenyl
iodonium hexafuoro antimonate

UTHSCSA Biomaterials 22
OPPI accelerates both LCM cure
rate & Deg. of Conversion
70%

60% Liq Crystal + OPPI

OPPI

50% Bis-GMA based

40%
Liq Crystal
30%

20%

10% + . . . it Reduces Yellow Color

0%
0 50 100 150 200 250 300
Degree of Conversion (% DC)
UTHSCSA Biomaterials Exposure Time (seconds) 23
 Single LC Monomer
Shortcomings
• Crystallize in the present of fillers
• Inadequate t - t range:
s→n n →i

 Shrinkage increases as t approaches

the n  i transformation temperature,
~45°C
 Mouth temp. shrinkage > RT shrinkage
UTHSCSA Biomaterials 24
 Blended Liquid
Crystal Monomer
Systems
SHELF-LIFE:
Strategy to prevent Liquid
Crystals from crystallizing in the
presence of reinforcing fillers
 Solution: LC-Monomer
Blends
• Blends prevent 3-dimensional order
 nucleated by inorganic fillers
 long-term stability against crystallization
• Co-synthesize a mixture of related
monomers in a “single pot”

UTHSCSA Biomaterials 26
 Sebacyl and Adipyl
t-butyl
O H CH 3

O O
O

O O H O
O

O
O H O O

O
O O

CH 3 H O
MW = 943

UTHSCSA Biomaterials 27
 16-component Liquid
Crystal Monomer Blend
QuickTime™ and a
decompressor
are needed to see this picture.

R3, 2 O

O R 2, 2 O R4
R1 O

O O O R 3, 1 CH2
O

O
CH2 R3,2 O O O

O
R4 O R2, 1 O

n
O R 3, 1

R4-CH3; R3,2 R3,1-H; R2,2-(CH2)4 or (CH2)8; R1-tC4H9 or CH3

bis (oxyethyl methacrylate) adipoate, A2 and sebacoate, S2

T and M represent R1-tC4H9 , CH3 ,
A and S represent R2,2-(CH2)4 and (CH2)8
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 NMR
Mole % 1.2 0.8 8.4 6.5 22.8 17.9 17.3 12.3 12.8

UTHSCSA Biomaterials 28
 Materials and methods
• 16-component blend was initiated with 1% CQ
and 2% DMAEMA.
• 75% 1 micron Ba-Glass filler, stored refrigerated.
• A control mixture of BisGMA 37.5% -TEGDMA
37.5% and BisEMA 25% was used for
comparison.
• Degree of conversion and initial cure rate were
measured by FTIR
• Volumetric shrinkage was measured in an Acuvol
• Transverse strength and moduli were measured
on 2 mm square beams in an Instron/MTS
UTHSCSA Biomaterials 29
 Cure Contraction

UTHSCSA Biomaterials 30
 Cure Characteristics
P=0.001

P=0.022

UTHSCSA Biomaterials 31
 Mechanical
Properties
Stress (MPa)
90

80
F
70

60

50

40
O
Y
SAMT
SAMT exhibits
exhibits aa high
high
30
degree
degree ofof shear
shear
M
yielding
yielding even
even at
at high
high
20 crosslink
crosslink density
density and
and
10
cure
cure
B
0
0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16
Strain (mm/mm)

UTHSCSA Biomaterials 32
Microtomed Photopolymerized SAMT Blend
& SAMT Composite (Crossed Polarizers)

SAMT SAMT COMPOSITE

500x Magnification 500x Magnification

10 µm 10 µm

LC state is maintained in the polymerized material

UTHSCSA Biomaterials 33
 Small Angle X-ray Diffraction of SAMT
4.5
Monomer blend and Polymer L=5.65nm

Smectic L=4.58nm

Liquid Crystal
4

3.5

Before Polymerization
3

2.5

1.5

After Photopolymerizaton
0.5

4.4 nm
0
Courtesy: S. Swinnea, UT Austin
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
2 theta
UTHSCSA Biomaterials 34
 Results
SAMT liquid crystal monomer blend:
 Composite does not crystallize
 Stable > 3 years Refrigerated
• In presence of high filler loading
 Shrinkage 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
UTHSCSA Biomaterials 35
 Biocompatibility
Studies
• LC-blend monomers and polymers
less cytotoxic than commercial
resins
• LC-blend restorative composite
utilized in ferret animal model with
no adverse effects

UTHSCSA Biomaterials 36
In Progress and Future Studies
• Synthesis simplification and scale-up.
• Eliminate smectic and phases in the
polymerized composite.
 Reduce light scattering to improve esthetic
properties
• Optimize particulate-filled formulations
 Nanoparticle reinforcing fillers
 Characterize wear resistance
• Clinical trials
UTHSCSA Biomaterials 37
 Acknowledgements
University
University of
of Texas
Texas HSC
HSC
Supported by: BK
BK Norling,
Norling, KK Whang,
Whang, Neera
Neera Satsangi,
Satsangi,VV Lee,
Lee,
NIH / NIDCR HL
HL Cardenas,
Cardenas, Q Q Whang
Whang

Grant numbers Southwest

Southwest Research
Research Institute
Institute
ST
ST Wellinghoff,
Wellinghoff, DD Nicolella,
Nicolella, H
H Dixon,
Dixon, D
D Hanson,
Hanson,
P01 DE11688 JJ McDonough,
McDonough, BR BR Furman,
Furman, PP Thompson
Thompson
R01 DE06179 Universities
Universities in,
in, South
South Korea
Korea
EssTech & Ultradent Y-J
Y-J Park,
Park, D.
D. Shen
Shen
(Monomers) Students
Students
Dental
Dental School,
School, Co*Star,
Co*Star, TAMU,
TAMU, UTSA,
UTSA, UW
UW at
at
Kerr, Schott Glas (fillers) St.
St. Louis,
Louis, UTHSCSA-Biomedical
UTHSCSA-Biomedical Engineering,
Engineering,
UTHSCSA & SwRI Health
Health Careers
Careers and
and Clark
Clark High
High Schools,
Schools, and
and
others
others TNTM
TNTM
internal funds
Advanced Dental Restorative Systems
NIDCR grant P01 DE11688
UTHSCSA Biomaterials 38
QUESTIONS ?
FTIR - Degree of Conversion H H

O O O O
R O O R
O O O O

• DC: 1608 cm-1 :

aromatic,
aromatic
Measured by internal
standard,
changes in remains
unchanged
aliphatic peak Deg. Conversion
=
1637 cm-1 :
vs. aliphatic
H
1-(h2/h1)*(H1/H2) x
double bonds 100
aromatic peak decrease

UTHSCSA Biomaterials 40
Volumetric Shrinkage
Acuvol™ Bisco Inc.

This instrument uses image

recognition by pixel contrast to
outline the specimen and calculate
the volume before and after
polymerization (Martin, 2001).
UTHSCSA Biomaterials 41
 Transverse Strength &
Modulus

UTHSCSA Biomaterials 42