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TiUnite – a unique biomaterial

by: Peter Schüpbach / Roland Glauser

A remarkable set of images displays the process of osseointegration as it’s never been revealed before.

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.

Nobel Biocare first introduced TiUnite to the market in 2000 on its Brånemark System implants, and then applied it to Replace Select in 2001. Today, TiUnite is available on all Nobel Biocare implants, including those with machined collars.

Unlike implants with machined surfaces, TiUnite has clinically demonstrated the ability to increase the predictability and speed at which dental implants osseointegrate through osteoconductive bone formation.1

TiUnite is formed by spark anodization in an electrolytic solution containing phosphoric acid. This results in a thickened titanium oxide layer (up to 10 microns) and a moderately rough porous surface topography (Ra 1.2). TiUnite contains anatase and rutile, the most important titanium oxides, and is thereby a highly crystalline biomaterial. Studies have also shown the presence of phosphorus in the oxide layer.2, 3 Thus, TiUnite may have both a topography-related as well as a chemistry-related effect on osseointegration.

This article explains how TiUnite interacts with living tissue and accelerates wound healing.

An inevitable chronology

Wound healing comprises a cascade of events that the body brings into play to resolve injury. Nature’s first priorities are to stop bleeding, restore function and to prevent infection. Generally, the wound-healing events are grouped into four phases: hemostasis, inflammatory, proliferative/ 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 negatively 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 transforming growth factor beta (TGF-b).

These factors play a crucial role in the regulation of the wound-healing cascade.4, 5 During the first ten minutes, 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 phase

The inflammatory phase begins minutes following the implant insertion and continues for approximately two days.

Neutrophils are the first cells attracted by chemical signals released by the platelets, followed by macrophages.

Both cell types will phagocytize small bone debris. The fibrin will be broken down by the enzyme plasmin and the debris will also be removed by the leukocytes. Fibrinolysis starts already during hemostasis but is slower and thereby contributes 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 provisional matrix.6

Day 3 to 5: The proliferative/repair phase

The proliferative phase is characterized by granulation tissue formation, angiogenesis, collagen deposition, and wound contraction. In granulation tissue formation, fibroblasts invade the wound and form a 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 contract themselves.

Now the benefit of the TiUnite topography comes into play as the moderately rough surface diminishes the ECM retraction from the surface— when compared to smooth surfaces—and inhibits its retraction from the surface. This is a prerequisite for osteoconductive bone formation as osteogenic cells, again attracted 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 migrate 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 osteogenesis already has reached the surface. At the front of bone formation they will become differentiated to osteoblasts. The latter will form the bone collagenous bone matrix, whichventually becomes mineralized, and woven bone is formed.

The strength of TiUnite in this phase of the wound healing is obvious: the porous surface is an ideal substrate for the migration of osteogenic cells along the surface3 and the surface properties (with Ra < 2 μm and Rm > 5 μm) are optimal for the differentiation of stem cells into osteogenic cells.7 According 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 matrix only perpendicularly to the surface— and thereby directly into the open TiUnite pores.3 A kinetic study about early bone formation with TiUnite showed initial bone formation and its direct anchorage already around day 7, thereby maintaining the primary stability.6

Conclusions

Taken together, the unique TiUnite properties allow teamplay between topography-related as well as chemistry- related factors to accelerate osseointegration.

Therefore, it’s not surprising that a variety of animal and human studies have demonstrated enhanced osseointegration, both in terms of speed and amount of bone-to-implant contact on par with that of hydroxyapatite surfaces, which many still consider the gold standard for osteoconductivity.8

From a clinical perspective, Ti-Unite has enabled the predictable application 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 immediate function solutions to a very high and very reliable level of success.9

More to explore:

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References

1 Glauser R, Portmann M, Ruhstaller P, Lundgren AK, Hammerle CH, and Gottlow J. Stability measurements of immediately loaded machined and oxidized implants in the posterior maxilla. A comparative clinical study using resonance frequency analysis. Appl Osseointegration Res 2001, 2:27-29

2 Hall J, Lausmaa J. Properties of a new porous oxide surface on titanium implants. Appl Osseointegration Res 2000, 1:5-8

3 Schupbach P, Glauser R, Rocci A, Martignoni M, Sennerby L, Lundgren A, Gottlow J. The human bone-oxidized titanium implant interface: A light microscopic, scanning electron microscopic, back-scatter scanning electron microscopic, and energy-dispersive x-ray study of clinically retrieved dental implants. Clin Implant Dent Relat Res 2005;7 Suppl 1:S36-43

4 Park JY, Gemmell CH, Davies JE. Platelet interactions with titanium: modulation of platelet activity by surface topography. Biomaterials 2001;22:2671-2682

5 Marx RE, Platelet concentrate: a strategy for accelerating and improving bone regeneration. In: Davies JE, ed. Bone engineering. Toronto: em squared Inc., 2000:447-53

6 Schupbach P, Dickinson DP, Lee J, Susin C, Wikesjoe U. Cellular cascades of bone formation to anodized titanium implant surfaces: a histologic study in dogs. Clin Oral Implants Res (in preparation)

7 Boyan BD and Schwartz Z. Modulation of osteogenesis via implant surface design. In: Davies JE, ed. Bone engineering. Toronto: em squared Inc., 2000:232-239

8 Zechner W, Tangl S, Furst G, Tepper G, Thams U, Mailath G, and Watzek G. Osseous healing characteristics of three different implant types. Clin Oral Implants Res 2003, 14:150-157

9 Glauser R. Implants with an oxidized surface placed predominantly in soft bone quality and subjected to immediate occlusal loading: results from a 7-year clinical follow-up. Clin Implant Dent Relat Res. 2011 May 25. doi: 10.1111/j.1708-8208.2011.00352.x. [Epub ahead of print]