1) Micro-rough implant surfaces like double acid etched surfaces promote faster osseointegration compared to machined surfaces due to increased protein absorption, fibrin clot retention, and stem cell differentiation. 2) Studies found double acid etched surfaces had greater bone contact area and initial anchorage due to interlocking of bone. They also identified three genes specifically related to osseointegration that were upregulated earlier around micro-rough surfaces. 3) One gene in particular, P4H, was expressed at higher levels on double acid etched surfaces and led to higher collagen production and mineralization, resulting in bone that was harder and stiffer forming around these surfaces.

1. 2. Recent Advances in Implant Surface
Science
Takahiro Ogawa DDS, PhD
Ichiro Nishimura DDS, PhD
John Beumer III DDS, MS
Division of Advanced Prosthodontics, Biomaterials and
Hospital Dentistry, UCLA
This program of instruction is protected by copyright ©. No portion of
this program of instruction may be reproduced, recorded or transferred
by any means electronic, digital, photographic, mechanical etc., or by
any information storage or retrieval system, without prior permission.

2. Titanium implant surfaces
1st Generation
Titanium machined surface
Titanium plasma spray surface
Sand blasted surfaces
Hydroxyl apatite coated titanium surfaces
Machined Titanium plasma Sand blasted
surface spray surface surface

3. Titanium Surfaces
Problems
Bone anchorage with machined surfaces was not
ideal in bone sites exhibiting thin cortical layers
combined with poor quality trabecular bone, such as
the posterior maxilla.
•Some of the initial titanium plasma spray
surfaces were excessively rough and giant
cells and macrophages were seen
phagocytizing portions of the surface
(particle disease).
•It was very difficult to remove the
contaminants from the original
sand blasted surfaces.
•The original plasma spray HA-CaP surfaces
were not predictable

4. Hydroxyl Apatite - CaP Coatings
Coatings of hydroxyl apatite, because of
their chemical similarity to bone, were
thought to be advantageous.
The HA – CaP surface is more
osteoinductive than titanium and this
leads to more rapid bone deposition
following implant placement.
However the original so-called HA
surfaced implants were mostly
composed of tri-calcium phosphate,

5. Mechanism of Action: HA-CaP Coatings
v During healing Calcium and
Phosphate ions are released
from the HA-CaP coating in the
peri-implant region
v This leads to the precipitation of a
biological apatite with various
proteins which serves as a
substrate for osteoblastic cells
producing bone
v The biological apatite substrate
promotes cell adhesion, cell
differentiation and the synthesis
of mineralized collagen

6. HA-CaP Coatings
HA surfaces were very osteo-conductive.
v At six weeks following placement the
bone appositional index is close to
70% for HA coated implants compared
to 30-50% for original titanium
surfaces (machined and TPS)
(Weinlander et al, 1993).
However:
v When the so-called plasma spray HA -
Cap surface becomes exposed to the
oral cavity it becomes contaminated
with oral bacteria

7. HA-CaP Coatings
Clinical Problems
l Colonization by
microorganisms leads to
circum-implant infections.
l Cracks and fissures in some
cases led to the entire loss of
the HA coating.
l These factors predisposed to
a higher rate of implant failure Note the loss of bone
than seen with titanium around these HA
coated implants 4
implants (Wheeler, 1996). years after insertion.

8. HA-CaP Coatings
v These data have led most clinicians to switch to the
titanium surfaces.
v However, new methods of applying the HA-CaP
coatings with nano-sized crystals are evolving
which result in direct bonding of bone to the
surface of the implant eliminating the cement line.
In summary, HA coated systems have provoked great
interest and enthusiasm because of there osteo-
conductivity. The initial problems associated with plasma
spray application are in the process of being overcome
and this type of surface may be the surface of the future.

9. Ideal Implant Surface Properties
v Promote adsorption of proteins
v Promote adhesion and differentiation of bone
producing cells
v Tissue integration

10. Implant Surface Science
v The biological events leading to osseointegration
are influenced by:
v Surface chemistry
v Surface topography of the implant
v Hydrophilicity of the surface (wetability)
v Research efforts in the last twenty years have
attempted to idealize these properties on dental
implants in order to:
v Decrease healing time
v Enable use in compromised bone sites
v Improve the quality of the bone implant interface

11. The Jane and Jerry Weintraub Center for
Reconstructive Biotechnology
UCLA School of Dentistry
Ichiro Nishimura DDS, PhD, Director
Takahiro Ogawa DDS, PhD
Neil Garrett PhD
Anna Jewitt PhD
Kumar Shah DDS
Eleni Roumanas DDS
Ting Ling Chang DDS
Evelyn Chung DDS
James Kelley DDS, MS
John Beumer DDS, MS

12. Uncovering the secrets of
l Discover insights into the molecular
basis of osseointegration
l Develop the next generation of implant
surfaces
l Objectives
l Earlierloading
l Immediate loading
l Predictability in compromised sites
*Ichiro Nishimura DDS, PhD and Takahiro Ogawa DDS, PhD

13. Titanium Implants - Surface Modifications
2nd Generation
1st break through
The micro-rough surface implants
Ti Grit blasted Electrolytically
Sand blast- Acid etched
enhanced
acid etched

14. Titanium Implants – 2nd Generation
Surface roughness (Micro-topography)
Electrolytically modified
Acid etched surfaces
Combination acid etched and sand blasted surfaces
1 micron

15. Titanium Implants - Surface Modifications
2nd Generation
1st break through
The micro-rough surface implants
How are the new surfaces different from the old surfaces?
Why do we get better bone anchorage with these new
surfaces?
Are these surfaces more bioreactive? Do they accelerate the
process of osseointegration?
If so, what has been the impact on implant biomechanics, early
and immediate loading and treatment planning?

16. Current Implant Surfaces
Micro-rough surface textures – Why are
they a significant improvement?
Initial stabilization is improved
Maximize the volume of interlocking mineralized bone with
the implant surface
Double acid Machined
Torque Removal etched surface
v Reverse torque test
v Data recorded in N/cm
v Double acid etched vs
Machined
v 2 month data (1997)
v 1, 2, 3 months (2001)
Klokkevold et al, 1997, 2001

17. Initial anchorage -Torque removal studies
v 10 New Zealand White Rabbits
v 2 Custom-designed implants (distal femur)
v Machined
v Double acid etched (Osseotite)
Klokkevold et al, 1997, 2001)

18. Initial anchorage -Torque removal studies
Reverse torque rotation to removal (failure)
Klokkevold et al,1997; 2001)

19. Initial anchorage -Torque removal studies
Results – 2 months data
Machined = 4.95 ± 1.61 Ncm
Double acid etched = 20.50 ± 6.59 Ncm
Klokkevold et al, 1997

20. Initial anchorage -Torque removal studies
Why the difference?
vBetter mechanical
anchorage?
vBone contact area?
vQuality of the bone
at the
interface?
Klokkevold et al, 1997

21. Titanium Implants - Surface Modification
Surface roughness and the bone contact area
Animal studies have shown that the bone contact
area achieved is 50% greater with micro -rough
surfaces as compared to machined surfaces
(Buser et al, 1991, Weinlander, 1993, Hamada, 1995,
Nishimura and Ogawa, 2000, 2003).

22. 50 µm
Histomorphometry
Acid etched vs Machine surface Near zone
Far zone
Machined
Acid etched
(%)
80
*
60
40 *
20
(Ogawa and
0
W2 W4 Nishimura, 2000,
Bone-implant 2003),
contact ratio

23. Bone contact area
Microrough surfaces (Weinlander et al, 2004)
Electrolytically Titanium Double acid Sandblast acid
Modified plasma spray etched etched

24. Implant anchorage data
Shear Strength obtained with a push out test
Studies
Acid etched Machined
surface surface
Experimental
Rat implant

25. Implant anchorage data
obtained with a push out test
This test measures the strength of
implant tissue interface rather than
Push-in value (N) the strength of the surrounding bone.
60 Machined
*
Etched
40
*
20 *
0
0 2 4 8 *p<0.05
Healing period (week)

26. Current Implant Surfaces
Micro-rough surfaces and osseointegration
What biologic phenomenon
are affected by the changes
in surface micro
topography?

27. Current Implant Surfaces
Why are these surfaces
more bioreactive?
vRate of plasma protein
absorption
vFibrin clot retention
vCell Adhesion
vCell differentiation
vGene expression

28. Rate of plasma protein absorption
v Rate of plasma protein absorption
v Enhanced by hydrophilic surfaces
v Enhanced by micro-rough surfaces
v Reduced as the surface ages
v Promotes cell adhesion
v Promotes cell differentiation

29. Fibrin Clot Retention
Micro-rough surfaces
vDavies (1998) showed that micro-rough
surfaces captured and retained the fibrin
clot initially deposited on the implant
surface more effectively than machined
surfaces
v As a result the initial crticial events
(plasma protein adsorption, clot formation,
angiogenesis, mesenchymal stem cell
migration etc.) associated with
osseointegration were facilitated.

30. Differentiation of mesenchymal stem
cells (MSC) into functioning
osteoblasts
Functioning osteoblast
vStem cells migrate to the implant surface and
into the osteotomy site via the fibrin network
vThe micro-rough facilitates this process

31. Micro – rough Implant Surfaces
Ogawa and Nishimura set out to determine whether or
not the double acid etched surface result in:
Earlier osseointegration?
Better bone anchorage?
Determine what factors are responsible for the different bone
profiles seen on different surface textures of titanium implants.
They were particularly interested in the gene expression of the
differentiating osteoblasts
Osseotite- Double Acid Etched

32. Gene expression data obtained with a T-cell
model developed by Davies
T-cell implant Machined Acid-etched
v They implanted T-cell implants into
the femurs of rats and retrieved the
specimens at various time intervals.
vThey hypothesized that gene
expression is controlled at local levels
by the surface texture of the implant.

33. Why was the double acid etched surface
superior to the machined surface?
Why was the bone different?
Nishimura and Ogawa suggested
several reasons including:
Bone repair and generation may not be the
primary prerequisite for osseointegration
Might it be an implant dependent mechanism?
Hypothesis:
A set of genes that are NOT involved in bone
repair initiate and/or regulate the process of
osseointegration Ogawa and Nishimura,
2000, 2002, and 2003

34. Purpose of the study
Identify the genes that are expressed around implants
but not in non-implant wound healing of bone.
Non-implant defect
Turned implant
Etched implant
Screening of candidate
osseointegration-specific genes
Differential display
polymerase chain
reaction (DD-PCR)

35. Testing the candidate DD-PCR products
From 1853 DD-PCR products,
19 implant-specific (- + +)
2 acid-etched-specific (- - +)
42 different clones
3 Osseointegration-specific genes
(TO1, TO2, TO3)

36. mRNA expression of TO1
Day 3 Week 1 Week 2 Week 4
Non-implant defect
Turned implant
Etched implant Untreated control
TO1
GAPDH
0.2
Etched implant Turned implant
0.1
Non-implant defect
Day 3 Week 1 Week 2 Week 4

37. mRNA expression of TO2
Day 3 Week 1 Week 2 Week 4
Non-implant defect
Turned implant
Etched implant Untreated control
TO2
GAPDH
0.6
0.4 Turned implant
Etched implant
0.2
Non-implant defect
Day 3 Week 1 Week 2 Week 4

38. mRNA expression of TO3
Day 3 Week 1 Week 2 Week 4
Non-implant defect
Turned implant
Etched implant Untreated control
TO3
GAPDH
1.2
Etched implant
0.8
Turned implant
0.4
Non-implant defect
Day 3 Week 1 Week 2 Week 4

39. TO genes showed
Osseointegration-specific expression
Upregulation in early stages of
implantation
Accelerated expression for the double
acid etched surface

40. TO3 happens to be P4H
Enhanced gene expression of
prolyl 4-hydroxylase (P4H)
Collagen synthesis considerably
higher

41. Collagen and P4H
-
P4H

42. Why was the accelerated
expression of P4H on micro-
rough surfaces significant?
Collagen density and orientation, as well as the
degree of mineralization are contributing
factors relative to the microhardness and elastic
modulus of bone

43. Bone Implant Interface
Double Acid Etched Surfaces
A different combination of collagenous and
noncollagenous proteins make up the bone deposited
on the dual acid etched surface as compared to a
machined surface.
Resorption and remodeling of bone deposited on acid
etched surfaces appeared to be different than bone
on machined surfaces.

44. Nano Indentation Test
3 times stiffer bone on dual acid etched
2000nm indentation depth
P=0.0252
Elastic modulus
P=0.0339
(GPa) 0.2
0.1
0
Bone on Bone on Bone on
Polystyrene Machined Ti DAE

45. Nano indentation test
2 times harder bone on dual acid etched
200mN maximum load
P=.0005
P=0.0153
P=0.0130
Nanohardness
(GPa)0.8
0.6
0.4
0.2
0
Bone on Bone on Bone on
Polystyrene Machined Ti DAE

46. Nanoindentation: in vivo bone
Bone around machined surfaces is as hard as the trabecular
bone, while the bone around the DAE surfaces is as hard as
the cortical bone. Ogawa et al, 2005

47. Day 28
Day 14
7
Day 21
0
3
Distinct pattern of osteogenesis on DAE
Osteoblast
Non-collagenous matrix
Mineral deposition
Collagen matrix

48. Current Implant Surfaces
Micro-rough surface textures – Why are they a
significant improvement
Shape of the cell affects its gene expression
and the micro-environment affects cell behavior.
Improved adsorption of plasma proteins

49. Micro-rough surfaces – Why are they superior?
vImproved clot retention (Davies, 1998)
vInitial absorption of plasma proteins is
enhanced (fibronectin, vitronectin etc) (Kohavi
(2010)
vMSC differentiate much faster on micro-
rough surfaces as compared to smooth
surfaces (Ogawa et al, 2003)
vMicro-rough surfaces changes gene
expression of the differentiating osteoblasts
(Ogawa and Nishimura (2000,2003 and 2004, 2006)
vBone deposited on micro-rough surfaces is
harder and stiffer than bone deposited on
machined surfaces (Butz,2006; Takeuchi et al,
2005)

50. Impact of Strengthened Peri-implant Bone
Trabecular
bone
Cortical
bone
Cortical bone:
l Very dense
l Less subject to
resorption or
remodeling

51. Enhancement of current titanium
surfaces
SLA active (implant packaged in saline)
(Strauman)
Maintains the wetability of the surface
Wetable surfaces significantly enhances
initial adsorption of plasma proteins
This, in turn facilitates migration, adhesion and
differentiation of mesenchymal stem cells

52. Other means of increasing
wetability of the implant surface
v Incorporate calcium, magnesium or
fluoride ions into the titanium oxide surface
v Thisis referred to as “electro-wetting” and
allows the plasma proteins to flow freely onto
the implant surface and into the irregularities
of the micro-roughened surface immediately
upon insertion of the implant

53. Enhancement of titanium surfaces
Fluoride treated surfaces (Astra)
vImproves the wetability of the surface
vCbfa expression is high for the grit
blasted fluoride prepared surface (Isa et
al, 2006)
Cbfa is a transcription protein that promotes
cell differentiation of osteoprogenitor cells)
Accelerates the events leading to
deposition of bone on the implant surface

54. Biological aging and
photofunctionalization
of TiO2
UV-treatment
Tak Ogawa DDS, PhD
Weintraub LA, UCLA

55. Biological aging and photofunctionalization
of TiO2
v Present day implants are packaged in plastic
v They are then sterilized with gamma radiation
v This process releases hydrocarbons which
contaminate the implant surface
Bioreactivity of the implant surface is impaired
The surface charge is changed from positive to
negative
The surface becomes less wetable
Adsorption of plasma proteins is inhibited

56. Impact of UV-treatment on
biomechanical strength
*p<0.0001
Original Light-treated **p<0.05
Push-in value
N=9
(N) 50 50 *
40 40 *
30 30
20 ** 20
** 10
10
0 0
Day 14 Day 28 Day 14 Day 28
Machined surface Acid-etched surface

57. Week 4 peri-implant bone morphogenesis
Bone contact area
*p<0.0001
Light-treated acid-etched surface Original Light N=4
100 *
80 *
60
40
20
0
Day 14 Day 28
Bone–implant contact

58. Control
UV-Effects (6 h)
v UV Enhanced protein absorption
vUV Enhanced migration of MSC
to Ti surface
v UV Promotes more rapid
differentiation of MSC into
functioning osteoblasts
v UV Enhanced adhesion, spreading
behavior and cytoskeleton
arrangement of osteoblasts
Light treated

59. Proposed mechanism for improved
osteoblast affinity on UV treated TiO2
Cx
Hy
UV-pretreated TiO2 TiO2
R
C
O O O
Ti4+ Ti4+
O (h+) O
hv Ti4+ Ti4+
O
Titanium Oxide is photocatalytic. Following UV exposure
free radicals are formed which absorb the hydrocarbons on
the implant surface.

60. Benefits of UV Light
v Improved wetability
v Changes the surface charge from negative
to positive
v These factors dramatically improve initial
absorption of plasma proteins during the
initial stages of healing (10-20 minutes
immediately following implant placement)
Aita et al, 2009; Atta et al, 2009

61. Benefits of UV Light
Possible future clinical applications
Treatment of the failing implant
v Decontaminating implant surfaces in vivo with UV
light
Courtesy G Perri

62. Titanium Implant Surfaces
1st generation 2nd generation 3rd generation
Machined surface Nano-enhanced
Ti blasted surface surfaces
Sand-blasted surface
v HA- CaP crystal
TPS Sand-blasted,
deposition
HA coated surface acid-etched vTitanium particle
(plasma spray) surface
Genetically
Dual acid-etched engineered
surface
Recombinant
Electrolytically proteins-BMP
enhanced

63. 3rd Generation of Implant Surfaces
Genetically engineered implant surfaces
Adding recombinant peptides to the surface
(BMP’s etc)
Nano-enhanced surface topography
Coatings to enhance surface chemistry
HA-CaP crystal deposition
Pico to nanometer thin TiO2 coating

64. Application of TO genes:
Non-viral Plasmid DNA
Gene Transfer
TO2

65. Impact of TO2 gene delivery (1 week)
P=.0055
Push-in value
(N) 16
14 DAE
12 Machined
10
8
6
4
2
0
Untreated Matrix
control TO2

66. Genetically Engineered Implant Surfaces
Potential advantages of
gene delivery
Doesn’t degrade
Low doses
Associated with the
! normal cell cascade
Disadvantages
Regulatory issues
Time to market
Cost/Benefit ratio

67. Surfaces enhanced with recombinant peptides
Recombinant peptide delivery (BMP-2) has not proven
to be effecticve. Why?
Production issues
During sterilization much of BMP may be deactivated
They require high doses which may be toxic
They are not associated with the normal ! cellular
cascade
Retention and release difficult to control
High cost
Schliephake et al, 2005

68. Nano-enhancement of the implant
surface
v Increased surface area
v Enhanced wetability and adsorption of
plasma proteins
v More favorable surface chemistry with HA-
CaP coatings and TiO2 pico-nanometer
coatings

69. Nanotechnology
Current
Defini6on
1. Size:
1
to
100
nanometer
range
2. Novel
proper6es
due
to
its
small
size
3. Incorporated
into
large
material
components
l Research and technology development at the atomic, molecular or macromolecular levels,
in the length scale of approximately 1 - 100 nanometer range, to provide a fundamental
understanding of phenomena and materials at the nanoscale and to create and use
structures, devices and systems that have novel properties and functions because of their
small and/or intermediate size. The novel and differentiating properties and functions are
developed at a critical length scale of matter typically under 100 nm.
l Nanotechnology research and development includes manipulation under control of the
nanoscale structures and their integration into larger material components, systems and
architectures. Within these larger scale assemblies, the control and construction of their
structures and components remains at the nanometer scale. In some particular cases, the
critical length scale for novel properties and phenomena may be under 1 nm (e.g.,
manipulation of atoms at ~0.1 nm) or be larger than 100 nm (e.g., nanoparticle reinforced
polymers have the unique feature at ~ 200-300 nm as a function of the local bridges or
bonds between the nano particles and the polymer).
l DEFINITION of NANOTECHNOLOGY by NSET, 2002: Subcommittee on Nanoscale
Science, Engineering and Technology for the U.S. National Science and Technology
Council under President G.W. Bush

70. Effect of Nano-Structure: Cell response
Overwhelming numbers of studies report significant
effect of nano-structure on cellular behaviors
Human
corneal
epithelial
cells
with
Fibroblast
growth
was
70nm
groove
(A)
or
flat
surface
(B) prohibited
on
nano-­‐structured
surface

71. Effect of Nano-Structure: Cell response
On nanometer particle size ceramics such as alumina,
titania and hydroxyapatite, osteoblast adhesion
increased while fibroblast adhesion decreased.
Osteoblast Fibroblast
Webster
et
al,
Biomaterials,
1999 Richert
et
al,
Orthoped
Res
Soc
abstract,
2006

72. Effect of Nano-Structure:
Controlled protein adsorption
v Protein adsorption to
nano-structured
surfaces requires
less energy than to
flat surface
v Nano-structure
orients the direction
of adsorbed protein
Sabirianov
et
al,
Enhanced
iniJal
protein
adsorpJon
on
engineered
nanostructured
cubic
zirconia

73. Effect of Nano-Structure:
Controlled protein adsorption
v Protein adsorption
increased
significantly on
~30nm structured
TiOx surface.
v Surface nano-
structure determines
the protein
adsorption
ScopelliJ
et
al,
The
effect
of
surface
nanometre-­‐scale
morphology
on
protein
adsorpJon,
PlosOne,
2010

74. Effect of Nano-Structure:
Long-term stability of osseointegration
v Recent theoretical
models indicates
increased
mechanical
interlocking of bone
with nano-structured
surfaces.
Loberg
et
al,
Open
Biomater
J,
2010
Hansson
et
al,
Open
Biomater
J,
2010

75. Conclusion
v In the advent of Nanotechnology development,
dental implant surface modifications now employ a
variety of new processing methods at nano-scales.
v While micro-structured implants entered in the
discount, generic manufacturing, nano-structured
implant surfaces present the new generation of
dental implants.
v Advantages of nano-structured implants include
selective cellular behaviors and controlled protein
adsorption leading to a “tailored” biological
regulation.
v Once osseointegration is established, bone-implant
mechanical interlocking may be better maintained
on the nano-structured implant, potentially
contributing to the long-term stability.

76. Nano-coating of HA-CaP Crystals
applied to the surface of the implant

77. Changes Nano-Surface Topography
and Chemistry
Before After

78. HA-CaP Coatings
Mechanism of Action
v During healing Calcium and Phosphate ions are released
from the HA-CaP coating in the peri-implant region
v This leads to the precipitation of a biological apatite with
various proteins incorporated which serves as a substrate
for osteoblastic cells producing bone
v The biological apatite substrate promotes cell adhesion,
cell differentiation and the synthesis of mineralized
collagen
v The CaP coatings promote direct bone bonding as
compared to noncoated surfaces

79. Shear Strength (MPa) DAE Ti-nanoHA
Chemical Bonding?
Machined Ti
DAE Ti
DAE Ti-nanoHA
Shear strength at 2 wk
S=F/A [N/mm2]

80. Synergistic effect of DAE topography and HA –
CaP nano-crystal deposition
Nishimura and
Butz et al, 2004
When nano-HA coating was added to conventional smooth and
DAE implants, bone anchorage was increased over 100%. In fact
DAE Ti-nanoHA implant showed the accelerated bone-implant
integration at the level that has never been reported.

81. Bone-implant integration
Machined DAE+HA-nano-topography
bone
Weak Link – Cement Line
Smooth implant was almost naked because surrounding bone
did not stay on implant.
DAE plus nano-HA was covered by the surrounding bone
indicating that bonding was so strong the push-in force
fractured the bone.

82. Bone-implant integration
Machined DAE+HA-nano-topography
bone
The bond between the bone and
implant surface was greater than
between the new bone and old bone.
No cement line?

83. HA – CaP Enhanced Surfaces
HA-Ca P crystal deposition
Additional advantages for potential future
applications
v Gene delivery
v Growth factors, osteogenic protein, antibiotic
delivery etc.

84. Titanium Implants - Surface Modifications
Nano-surface modification of titanium surface
Further enhancement of the surface topography by physical
vapor deposition (Ogawa et al, 2007; Sugita et al, 2011)
l Increased surface area for bone deposition
l Surface topography created similar to mineralized bone matrix
l Enhanced osteoblast adhesion, proliferation and differentiation
l Promotion of osteoblast function
l Greater strength of osseointegration

85. Pico-super-thin surface
modification of Ti
v Ogawa and associates have shown that a pico-
meter thin TiO2 coating improves the
bioreactivity of microrough implant surfaces by
modulating its surface chemistry while
preserving the existing surface morphology
Sugita et al, 2011

86. Pico-super-thin surface modification of TiO2
Method
Slow-rate sputter coating of liquidified nanoscale
TiO2 particles
Optimal exposure time – 15 min
Liquidified TiO2-
Control Ti coated Ti
Sugita et al, 2011

87. No surface thin as 300 pm change before and after
As topography
The coating is as thin as 300 pm
Control Ti Liquid TiO2 - 15 min
The micro-rough topgraphy is unchanged by the coating
Sugita et al, 2011

88. Effects of pico-nanometer TiO2 Coating
Impact on osteoblasts
v Improves cell attachment
v Enhances spreading behavior
v Increased proliferation
v Accelerates differentiation

89. Enhanced bone cell attachment (6 h)
P<0.05
WST-1/cell
0.2
0.1
0
Control Ti Liquid TiO2 coated
N=3
Sugita et al, 2011

90. Expedited and enhanced
Enhanced Cell spreading and
cellular settlement and spread
cytoskeleton arrangement of osteoblasts
Control Ti Liquid TiO2 coated
Overlay Overlay min
15
50µm 50µm
Uncoated surface 15 minute TiO2 coated surface
Sugita et al, 2011

91. Increased osteoblast
proliferation (Day 2)
P<0.05
BrdU incorporation
/ cell
0.3
0.2
0.1
0
Untreated Liquid TiO2 coated
N=3 Sugita et al, 2011

92. Rate of Osteoblastic
Differentiation Enhanced bone cell
function (Day 5)
P<0.05
ALP activity
0.15
0.1
0.05
0
Untreated Liquid TiO2 coated N=3
Sugita et al, 2011

93. Bone-related gene expression (Days 7 and 14)
Sugita et
al, 2011

94. Mineral deposition (Day 14)
Sugita et al, 2011

95. Control Liquid TiO2 coated
Mineralized nodule
area at day 14
(arizarin red)
Control Liquid TiO2 coated
Sugita et al, 2011

96. Significance:
vFor the first time, pico-super-thin
coating of TiO2 was applied, which
did not to alter the existing micro -
topography of Ti.
vSurface chemistry of TiO2 is an
important factor determining the
bioreactivity of the implant surface.
vThis technology may have opened
a new avenue of surface
enhancement for endosseous
implants. Sugita et al, 2011

97. Clinical Impact of advances in
implant surface science?
The biologic events leading to
osseointegration have been accelerated
Better bone anchorage

98. Implants in Compromised Sites
Can we use shorter implants?
Posterior maxilla
Posterior mandible over the
inferior alveolar nerve in partially
edentulous patients
Craniofacial application Theoretically perhaps.
However we need well
designed clinical
outcome studies to
determine predictability

99. Coming soon
vEdentulous Mandible – Overlay Dentures
vEdentulous Maxilla – Overlay Dentures

100. v Visit ffofr.org for hundreds of additional lectures
on Complete Dentures, Implant Dentistry,
Removable Partial Dentures, Esthetic Dentistry
and Maxillofacial Prosthetics.
v The lectures are free.
v Our objective is to create the best and most
comprehensive online programs of instruction in
Prosthodontics