Nobel Biocare NEWS Issue 1/20128

Implant surface properties are of key importance for initial tissue interactions, the acceleration of bone healing and osseointegration. TiUnite is titanium oxide rendered into an osteoconductive biomaterial through spark anodization. New insights explain how TiUnite interacts with tissue and why it remains the osteoconductive surface of choice.

By Drs. Peter Schüpbach and Roland Glauser

Nobel Biocare first introduced TiUnite to the market in on its Brånemark Sys-

tem implants, and then applied it to Replace Select in . Today, TiUnite is available on all Nobel Biocare implants, including those with machined collars.

Unlike implants with machined surfaces, TiUnite has clinically dem-onstrated the ability to increase the predictability and speed at which dental implants osseointegrate through osteoconductive bone for-mation (Glauser et al, ).

TiUnite is formed by spark anod-ization in an electrolytic solution containing phosphoric acid. This re-sults in a thickened titanium oxide layer (up to microns) and a mod-erately rough porous surface topog-raphy (Ra .). TiUnite contains ana-tase and rutile, the most important

Platelet activation: Immediately following implant insertion, blood proteins and platelets are attracted by the negatively charged TiUnite surface. The activated platelets form pseudopodia and clump together to form aggregates.

Hemostasis: Blood clot formation will be accomplished by the formation of the fibrin matrix. Activated platelets (arrows) become embedded in the matrix. Eventually, the platelets start to release granules containing full batteries of enzymes and growth factors needed for the wound healing.

TiUnite® – A Unique BiomaterialA remarkable set of images displays the process of osseointegration as it’s never been revealed before.

titanium oxides, and is thereby a highly crystalline biomaterial. Stud-ies have also shown the presence of phosphorus in the oxide layer (Laus-maa & Hall, ; Schüpbach et al, ). Thus, TiUnite may have both a topography-related as well as a chemistry-related effect on osseoin-tegration.

This article explains how TiUnite interacts with living tissue and ac-celerates wound healing.

An inevitable chronologyWound healing comprises a cascade of events that the body brings into play to resolve injury. Nature’s first

priorities are to stop bleeding, re-store function and to prevent infec-tion. Generally, the wound-healing events are grouped into four phases: hemostasis, inflammatory, prolifer-ative/repair, and remodeling.

Hemostasis (0 to 10 minutes following implant placement)TiUnite shows its strength already at the time of placement of an implant: Within seconds, blood proteins and platelets are attracted to the nega-tively charged TiUnite surface and become immediately activated.

This first step is crucial for the wound healing. Their activation is followed by the release of growth factors, such as platelet-derived growth factor (PDGF) and trans-forming growth factor beta (TGF-b).

These factors play a crucial role in the regulation of the wound-healing

cascade (Park JY et al, ; Marx RE, ). During the first ten min-utes, fibrin—the reaction product of thrombin and fibrinogen—will be released at the wound site.

The resulting stabilized blood clot reveals improved adherence to the moderately rough TiUnite surface when compared to smooth surface implants.

Day 1 to 2 The inflammatory phaseThe inflammatory phase begins minutes following the implant in-sertion and continues for approxi-mately two days.

Neutrophils are the first cells at-tracted by chemical signals released by the platelets, followed by macro-phages. Both cell types will phago-cytize small bone debris. The fibrin will be broken down by the enzyme

plasmin and the debris will also be removed by the leukocytes. Fibrino-lysis starts already during hemosta-sis but is slower and thereby con-tributes to its regulation.

The breakdown of the fibrin clot creates the room in the wound site needed for the invasion of fibroblast and thereby the forming of the pro-visional matrix (Schüpbach et al, in preparation).

Day 3 to 5The proliferative/repair phaseThe proliferative phase is character-ized by granulation tissue forma-tion, angiogenesis, collagen deposi-tion, and wound contraction. In granulation tissue formation, fibro-blasts invade the wound and form a

S&ESafety and Efficacy

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Nobel Biocare NEWSIssue 1/2012 9

Recent Findings

TiUnite® 10-year, Immediate Loading Already available as an ePub ahead of publication, an article in “Clinical Implant Dentistry and Related Research” documents the 10-year outcome of immediately loaded implants with the TiUnite surface.

“10-Year Follow-Up of Immediately Loaded Implants with TiUnite Porous Anodized Surface,“ by Drs. Marco Degidi, Diego Nardi and Adriano Piattelli reports on a prospective study the authors carried out to assess the 10-year performance of TiUnite implants supporting fixed prostheses placed with an immediate loading approach in both postextractive and healed sites.

All the patients in this study received a fixed provisional restoration supported by parallel design, self-tapping implants with a TiUnite sur-face, and an external hexagonal connection.

Success and survival rate for restorations and implants, changes in marginal peri-implant bone level, probing depth measurements, biologi-cal or technical complications, and any other adverse event were recorded at yearly follow-ups.

The implants placed in healed and post-extractive sites, respectively, achieved a 98.05% and a 96.52% cumulative survival rate and the authors conclude that positive results—in terms of bone maintenance in the long-term perspective—are to be expected using immediately loaded implants with a TiUnite surface in both post-extractive and healed sites when adequate levels of oral hygiene are maintained.

www.nobelbiocare.com/tiunite-10-year-abstract

7-year TiUnite® Overdenture StudyAlso available as an ePub, another study to be published in “Clinical Implant Dentistry and Related Research” follows up seven years of experience with the implant-supported mandibular overdentures that have become a popular treatment alternative for edentulous patients desiring increased retention of complete dentures.

“Seven-year Follow-up Results of TiUnite Implants Supporting Mandib-ular Overdentures: Early versus Delayed Loading,” by Drs. Ilser Tur-kyilmaz, Tolga F. Tozum, Dana M. Fuhrmann and Celal Tumer, evaluates and presents treatment outcomes of mandibular overdentures retained by two unsplinted, early-loaded implants and compares these results with those for delayed-loaded implants.

No implant was lost in this clinical trial, and the results show that there is no significant difference in the clinical and radiographic outcomes of patients treated with mandibular overdentures supported by TiUnite implants that are either early or delayed loaded.

www.nobelbiocare.com/overdenture-abstract

Over 11 million TiUnite® Implants Sold to Date!Scientific studies on TiUnite have demonstrated over and over again this surface’s ability to increase the predict-ability and speed of dental implant osseointegration. Help us celebrate a decade of success by reading all about it:

More to explore: nobelbiocare.com/resources

Early wound healing: The fibrin matrix will be broken down by the enzyme plasmin and their debris will be removed by neutrophils (green, left) and later macrophages. The healing site will be invaded by fibroblasts and the blood clot replaced by the provisional extracellular matrix. Eventually, osteogenic cells (red arrows) stream to the implant surface. Once they reach it, they migrate by active locomotion using their pseudopodia and the open pores as attachment points (yellow arrow) to the front of bone formation.

Osteoconductive bone formation: Human histology six months following insertion shows bone anchored in the TiUnite pores (left). In extraction sockets, newly formed bone crosses the gap between local bone (LB) and the implant surface by distance osteogenesis (middle, yellow arrow). As soon as the implant surface is reached, new bone spreads over the surface by contact osteogenesis (middle, red arrow) characterized by woven bone deposited directly on and along the surface (right).

provisional extracellular matrix (ECM) by secreting collagen and fibronectin. In angiogenesis, new blood vessels are formed by vascular endothelial cells. In contraction, the wound is made smaller by the action of myofibroblasts, which establish a grip on the wound edges and con-tract themselves.

Now the benefit of the TiUnite topography comes into play as the moderately rough surface diminish-es the ECM retraction from the sur-face—when compared to smooth surfaces—and inhibits its retraction from the surface. This is a prerequi-site for osteoconductive bone forma-tion as osteogenic cells, again attract-ed by the chemical signals of the platelets, may reach the surface only if the ECM remains attached.

Day 5 to 7 – Osteoconductive bone formation Once the osteogenic cells have reached the TiUnite surface, they mi-grate to the front of bone formation, i.e. where wound edges of the local bone of the osteotomy are in contact with the implant surface or where bone newly formed by distance os-teogenesis already has reached the surface. At the front of bone forma-tion they will become differentiated to osteoblasts. The latter will form

the bone collagenous bone matrix, which eventually becomes mineral-ized, and woven bone is formed.

The strength of TiUnite in this phase of the wound healing is obvi-ous: the porous surface is an ideal substrate for the migration of osteo-genic cells along the surface (Schüp-bach et al, ) and the surface properties (with Ra < μm and Rm

>  μm) are optimal for the differen-tiation of stem cells into osteogenic cells (Schwartz et al, ). Accord-ing to these characteristics, TiUnite is highly osteoconductive and new bone formation occurs rapidly and directly on and along the implant surface.

Moreover, the osteoblasts, being polarized cells, secrete collagen ma-trix only perpendicularly to the sur-face—and thereby directly into the open TiUnite pores (Schüpbach et al, ). A kinetic study about early bone formation with TiUnite showed initial bone formation and its direct anchorage already around day , thereby maintaining the primary sta-bility (Schüpbach et al, in prep.).

“The TiUnite surface has improved our results, especially in grafted bone and in bone of low density. It has, without question, significantly reduced our early failure rate as well.”

— Professor Bertil Friberg, Sweden

ConclusionsTaken together, the unique TiUnite properties allow teamplay between topography-related as well as chem-istry-related factors to accelerate osseointegration.

Therefore, it’s not surprising that a variety of animal and human studies have demonstrated enhanced osseo-integration, both in terms of speed

and amount of bone-to-implant contact on par with that of hydroxy-apatite surfaces, which many still consider the gold standard for osteo-conductivity (Zechner et al, ).

From a clinical perspective, Ti-Unite has enabled the predictable ap-plication of very short implants and implants placed in very demanding bone conditions. Moreover, TiUnite has both reduced the healing time necessary before functional implant loading can take place, and lifted im-mediate function solutions to a very high and very reliable level of success (Glauser ). <

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