Recent Advances in Implant Surface Science


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Recent Advances in Implant Surface Science

  1. 1. 2. Recent Advances in Implant Surface Science Takahiro Ogawa DDS, PhD Ichiro Nishimura DDS, PhD John Beumer III DDS, MSDivision 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. 2. Titanium implant surfaces 1st GenerationTitanium machined surfaceTitanium plasma spray surfaceSand blasted surfacesHydroxyl apatite coated titanium surfaces Machined Titanium plasma Sand blasted surface spray surface surface
  3. 3. Titanium SurfacesProblems 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. 4. Hydroxyl Apatite - CaP CoatingsCoatings of hydroxyl apatite, because oftheir chemical similarity to bone, werethought to be advantageous.The HA – CaP surface is moreosteoinductive than titanium and thisleads to more rapid bone depositionfollowing implant placement.However the original so-called HAsurfaced implants were mostlycomposed of tri-calcium phosphate,
  5. 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. 6. HA-CaP CoatingsHA 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. 7. HA-CaP Coatings Clinical Problemsl 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. 8. HA-CaP Coatingsv 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. 9. Ideal Implant Surface Propertiesv Promote adsorption of proteinsv Promote adhesion and differentiation of bone producing cellsv Tissue integration
  10. 10. Implant Surface Sciencev 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. 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. 12. Uncovering the secrets ofl Discover insights into the molecular basis of osseointegrationl Develop the next generation of implant surfacesl Objectives l Earlierloading l Immediate loading l Predictability in compromised sites*Ichiro Nishimura DDS, PhD and Takahiro Ogawa DDS, PhD
  13. 13. Titanium Implants - Surface Modifications 2nd Generation 1st break through The micro-rough surface implantsTi Grit blasted Electrolytically Sand blast- Acid etched enhanced acid etched
  14. 14. Titanium Implants – 2nd GenerationSurface roughness (Micro-topography) Electrolytically modified Acid etched surfaces Combination acid etched and sand blasted surfaces 1 micron
  15. 15. Titanium Implants - Surface Modifications 2nd Generation 1st break through The micro-rough surface implantsHow are the new surfaces different from the old surfaces?Why do we get better bone anchorage with these newsurfaces?Are these surfaces more bioreactive? Do they accelerate theprocess of osseointegration?If so, what has been the impact on implant biomechanics, earlyand immediate loading and treatment planning?
  16. 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 MachinedTorque 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. 17. Initial anchorage -Torque removal studiesv 10 New Zealand White Rabbitsv 2 Custom-designed implants (distal femur) v Machined v Double acid etched (Osseotite) Klokkevold et al, 1997, 2001)
  18. 18. Initial anchorage -Torque removal studies Reverse torque rotation to removal (failure) Klokkevold et al,1997; 2001)
  19. 19. Initial anchorage -Torque removal studies Results – 2 months data Machined = 4.95 ± 1.61 Ncm Double acid etched = 20.50 ± 6.59 NcmKlokkevold et al, 1997
  20. 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. 21. Titanium Implants - Surface Modification Surface roughness and the bone contact areaAnimal studies have shown that the bone contactarea achieved is 50% greater with micro -roughsurfaces as compared to machined surfaces(Buser et al, 1991, Weinlander, 1993, Hamada, 1995,Nishimura and Ogawa, 2000, 2003).
  22. 22. 50 µm HistomorphometryAcid 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. 23. Bone contact area Microrough surfaces (Weinlander et al, 2004)Electrolytically Titanium Double acid Sandblast acid Modified plasma spray etched etched
  24. 24. Implant anchorage dataShear Strength obtained with a push out test StudiesAcid etched Machined surface surface Experimental Rat implant
  25. 25. Implant anchorage data obtained with a push out test This test measures the strength of implant tissue interface rather thanPush-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. 26. Current Implant SurfacesMicro-rough surfaces and osseointegration What biologic phenomenon are affected by the changes in surface micro topography?
  27. 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. 28. Rate of plasma protein absorptionv Rate of plasma protein absorption v Enhanced by hydrophilic surfaces v Enhanced by micro-rough surfaces v Reduced as the surface agesv Promotes cell adhesionv Promotes cell differentiation
  29. 29. Fibrin Clot Retention Micro-rough surfacesvDavies (1998) showed that micro-roughsurfaces captured and retained the fibrinclot initially deposited on the implantsurface more effectively than machinedsurfacesv As a result the initial crticial events(plasma protein adsorption, clot formation,angiogenesis, mesenchymal stem cellmigration etc.) associated withosseointegration were facilitated.
  30. 30. Differentiation of mesenchymal stem cells (MSC) into functioning osteoblasts Functioning osteoblastvStem cells migrate to the implant surface and into the osteotomy site via the fibrin networkvThe micro-rough facilitates this process
  31. 31. Micro – rough Implant SurfacesOgawa and Nishimura set out to determine whether ornot the double acid etched surface result in: Earlier osseointegration? Better bone anchorage? Determine what factors are responsible for the different boneprofiles seen on different surface textures of titanium implants.They were particularly interested in the gene expression of thedifferentiating osteoblasts Osseotite- Double Acid Etched
  32. 32. Gene expression data obtained with a T-cell model developed by DaviesT-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. 33. Why was the double acid etched surfacesuperior to the machined surface?Why was the bone different?Nishimura and Ogawa suggestedseveral 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. 34. Purpose of the studyIdentify the genes that are expressed around implantsbut 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. 35. Testing the candidate DD-PCR products From 1853 DD-PCR products, 19 implant-specific (- + +) 2 acid-etched-specific (- - +) 42 different clones3 Osseointegration-specific genes (TO1, TO2, TO3)
  36. 36. mRNA expression of TO1 Day 3 Week 1 Week 2 Week 4 Non-implant defect Turned implant Etched implant Untreated control TO1GAPDH 0.2 Etched implant Turned implant 0.1 Non-implant defect Day 3 Week 1 Week 2 Week 4
  37. 37. mRNA expression of TO2 Day 3 Week 1 Week 2 Week 4 Non-implant defect Turned implant Etched implant Untreated control TO2GAPDH 0.6 0.4 Turned implant Etched implant 0.2 Non-implant defect Day 3 Week 1 Week 2 Week 4
  38. 38. mRNA expression of TO3 Day 3 Week 1 Week 2 Week 4 Non-implant defect Turned implant Etched implant Untreated control TO3GAPDH 1.2 Etched implant 0.8 Turned implant 0.4 Non-implant defect Day 3 Week 1 Week 2 Week 4
  39. 39. TO genes showedOsseointegration-specific expressionUpregulation in early stages of implantationAccelerated expression for the double acid etched surface
  40. 40. TO3 happens to be P4H Enhanced gene expression of prolyl 4-hydroxylase (P4H) Collagen synthesis considerably higher
  41. 41. Collagen and P4H -P4H
  42. 42. Why was the accelerated expression of P4H on micro- rough surfaces significant?Collagen density and orientation, as well as thedegree of mineralization are contributingfactors relative to the microhardness and elasticmodulus of bone
  43. 43. Bone Implant Interface Double Acid Etched SurfacesA different combination of collagenous andnoncollagenous proteins make up the bone depositedon the dual acid etched surface as compared to amachined surface.Resorption and remodeling of bone deposited on acidetched surfaces appeared to be different than boneon machined surfaces.
  44. 44. Nano Indentation Test 3 times stiffer bone on dual acid etched 2000nm indentation depth P=0.0252Elastic modulus P=0.0339 (GPa) 0.2 0.1 0 Bone on Bone on Bone on Polystyrene Machined Ti DAE
  45. 45. Nano indentation test 2 times harder bone on dual acid etched 200mN maximum load P=.0005 P=0.0153 P=0.0130Nanohardness (GPa)0.8 0.6 0.4 0.2 0 Bone on Bone on Bone on Polystyrene Machined Ti DAE
  46. 46. Nanoindentation: in vivo boneBone around machined surfaces is as hard as the trabecularbone, while the bone around the DAE surfaces is as hard asthe cortical bone. Ogawa et al, 2005
  47. 47. Day 28 Day 14 7 Day 21 0 3Distinct pattern of osteogenesis on DAE Osteoblast Non-collagenous matrix Mineral deposition Collagen matrix
  48. 48. Current Implant SurfacesMicro-rough surface textures – Why are they a significant improvementShape of the cell affects its gene expressionand the micro-environment affects cell behavior. Improved adsorption of plasma proteins
  49. 49. Micro-rough surfaces – Why are they superior?vImproved clot retention (Davies, 1998)vInitial absorption of plasma proteins isenhanced (fibronectin, vitronectin etc) (Kohavi(2010)vMSC differentiate much faster on micro-rough surfaces as compared to smoothsurfaces (Ogawa et al, 2003)vMicro-rough surfaces changes geneexpression of the differentiating osteoblasts(Ogawa and Nishimura (2000,2003 and 2004, 2006)vBone deposited on micro-rough surfaces isharder and stiffer than bone deposited onmachined surfaces (Butz,2006; Takeuchi et al,2005)
  50. 50. Impact of Strengthened Peri-implant Bone Trabecular bone Cortical boneCortical bone: l Very dense l Less subject to resorption or remodeling
  51. 51. Enhancement of current titanium surfacesSLA 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. 52. Other means of increasing wetability of the implant surfacev 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. 53. Enhancement of titanium surfacesFluoride 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. 54. Biological aging andphotofunctionalization of TiO2 UV-treatment Tak Ogawa DDS, PhD Weintraub LA, UCLA
  55. 55. Biological aging and photofunctionalization of TiO2v Present day implants are packaged in plasticv They are then sterilized with gamma radiationv 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. 56. Impact of UV-treatment on biomechanical strength *p<0.0001 Original Light-treated **p<0.05Push-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. 57. Week 4 peri-implant bone morphogenesis Bone contact area *p<0.0001Light-treated acid-etched surface Original Light N=4 100 * 80 * 60 40 20 0 Day 14 Day 28 Bone–implant contact
  58. 58. Control UV-Effects (6 h)v UV Enhanced protein absorptionvUV Enhanced migration of MSC to Ti surfacev UV Promotes more rapid differentiation of MSC into functioning osteoblastsv UV Enhanced adhesion, spreading behavior and cytoskeleton arrangement of osteoblasts Light treated
  59. 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+ OTitanium Oxide is photocatalytic. Following UV exposurefree radicals are formed which absorb the hydrocarbons onthe implant surface.
  60. 60. Benefits of UV Lightv Improved wetabilityv Changes the surface charge from negative to positivev 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. 61. Benefits of UV Light Possible future clinical applicationsTreatment of the failing implant v Decontaminating implant surfaces in vivo with UV light Courtesy G Perri
  62. 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. 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. 64. Application of TO genes: Non-viral Plasmid DNA Gene Transfer TO2
  65. 65. Impact of TO2 gene delivery (1 week) P=.0055Push-in value (N) 16 14 DAE 12 Machined 10 8 6 4 2 0 Untreated Matrix control TO2
  66. 66. Genetically Engineered Implant SurfacesPotential advantages of gene delivery Doesn’t degrade Low doses Associated with the ! normal cell cascadeDisadvantages Regulatory issues Time to market Cost/Benefit ratio
  67. 67. Surfaces enhanced with recombinant peptidesRecombinant 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. 68. Nano-enhancement of the implant surfacev Increased surface areav Enhanced wetability and adsorption of plasma proteinsv More favorable surface chemistry with HA- CaP coatings and TiO2 pico-nanometer coatings
  69. 69. Nanotechnology Current  Defini6on 1. Size:  1  to  100  nanometer  range 2. Novel  proper6es  due  to  its  small  size 3. Incorporated  into  large  material  componentsl 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. 70. Effect of Nano-Structure: Cell response Overwhelming numbers of studies report significant effect of nano-structure on cellular behaviorsHuman  corneal  epithelial  cells  with   Fibroblast  growth  was  70nm  groove  (A)  or  flat  surface  (B) prohibited  on  nano-­‐structured   surface
  71. 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. 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 proteinSabirianov  et  al,  Enhanced  iniJal  protein  adsorpJon  on  engineered  nanostructured  cubic  zirconia  
  73. 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 adsorptionScopelliJ  et  al,  The  effect  of  surface  nanometre-­‐scale  morphology  on  protein  adsorpJon,  PlosOne,  2010  
  74. 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. 75. Conclusionv 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. 76. Nano-coating of HA-CaP Crystalsapplied to the surface of the implant
  77. 77. Changes Nano-Surface Topography and Chemistry Before After
  78. 78. HA-CaP CoatingsMechanism 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. 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. 80. Synergistic effect of DAE topography and HA – CaP nano-crystal deposition Nishimura and Butz et al, 2004When nano-HA coating was added to conventional smooth andDAE implants, bone anchorage was increased over 100%. In factDAE Ti-nanoHA implant showed the accelerated bone-implantintegration at the level that has never been reported.
  81. 81. Bone-implant integration Machined DAE+HA-nano-topography boneWeak Link – Cement Line Smooth implant was almost naked because surrounding bonedid not stay on implant. DAE plus nano-HA was covered by the surrounding boneindicating that bonding was so strong the push-in forcefractured the bone.
  82. 82. Bone-implant integration Machined DAE+HA-nano-topography boneThe bond between the bone andimplant surface was greater thanbetween the new bone and old bone. No cement line?
  83. 83. HA – CaP Enhanced Surfaces HA-Ca P crystal depositionAdditional advantages for potential futureapplications v Gene delivery v Growth factors, osteogenic protein, antibiotic delivery etc.
  84. 84. Titanium Implants - Surface ModificationsNano-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. 85. Pico-super-thin surface modification of Tiv 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. 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. 87. No surface thin as 300 pm change before and after As topography The coating is as thin as 300 pmControl Ti Liquid TiO2 - 15 minThe micro-rough topgraphy is unchanged by the coating Sugita et al, 2011
  88. 88. Effects of pico-nanometer TiO2 CoatingImpact on osteoblasts v Improves cell attachment v Enhances spreading behavior v Increased proliferation v Accelerates differentiation
  89. 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. 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 50µmUncoated surface 15 minute TiO2 coated surface Sugita et al, 2011
  91. 91. Increased osteoblast proliferation (Day 2) P<0.05BrdU incorporation/ cell 0.3 0.2 0.1 0 Untreated Liquid TiO2 coated N=3 Sugita et al, 2011
  92. 92. Rate of Osteoblastic Differentiation Enhanced bone cell function (Day 5) P<0.05ALP activity 0.15 0.1 0.05 0 Untreated Liquid TiO2 coated N=3 Sugita et al, 2011
  93. 93. Bone-related gene expression (Days 7 and 14) Sugita et al, 2011
  94. 94. Mineral deposition (Day 14) Sugita et al, 2011
  95. 95. Control Liquid TiO2 coatedMineralized nodule area at day 14 (arizarin red) Control Liquid TiO2 coated Sugita et al, 2011
  96. 96. Significance:vFor the first time, pico-super-thincoating of TiO2 was applied, whichdid not to alter the existing micro -topography of Ti.vSurface chemistry of TiO2 is animportant factor determining thebioreactivity of the implant surface.vThis technology may have openeda new avenue of surfaceenhancement for endosseousimplants. Sugita et al, 2011
  97. 97. Clinical Impact of advances in implant surface science?The biologic events leading toosseointegration have been acceleratedBetter bone anchorage
  98. 98. Implants in Compromised Sites Can we use shorter implants?Posterior maxillaPosterior mandible over theinferior alveolar nerve in partiallyedentulous patientsCraniofacial application Theoretically perhaps. However we need well designed clinical outcome studies to determine predictability
  99. 99. Coming soonvEdentulous Mandible – Overlay DenturesvEdentulous Maxilla – Overlay Dentures
  100. 100. v Visit 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