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MetAlive® on tutkittu tieteellisesti, materiaalin ominaisuuksien ja solujen käyttäytymisen osalta, sekä kliinisissä sovelluksissa. Miksi ja miten MetAlive® toimii ja mitä kliinisiä etuja nopeammasta paranemisesta voi odottaa... (in english)

MetAlive® - solution for non-problematic wound healing

Look at the wound healing steps and then the evidence how MetAlive® effects them, to understand why the attachment is important to achieving a proper healing and a long term sustainable biological width. 

Wound healing steps

wound healing steps

 

Blood clotting

Within minutes post-injury, platelets (thrombocytes) aggregate at the injury site to form a fibrin clot. This clot acts to control active bleeding

Inflammatory

In the inflammatory phase, bacteria and debris are phagocytosed (eaten by cells) and removed, and factors are released that cause the migration and division of cells involved in the proliferative phase.

Proliferative

Proliferative The proliferative phase is characterized by angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction. angiogenesis, new blood vessels are formed by vascular endothelial cells.fibroplasia and granulation tissue formation, fibroblasts grow and form a new, provisional extracellular matrix (ECM) by excreting collagen and fibronectin. Concurrently, re-epithelialization of the epidermis occurs, in which epithelial cells proliferate and 'crawl' atop the wound bed, providing cover for the new tissue (in case of skin and mucosal tissue).
In contraction, the wound is made smaller by the action of myofibroblasts, which establish a grip on the wound edges and contract themselves using a mechanism similar to that in smooth muscle cells. When the cells' roles are close to complete, unneeded cells undergo apoptosis (cell death).

Maturation and Remodeling

In the maturation and remodeling phase, collagen is remodeled and realigned along tension lines and cells that are no longer needed are removed by apoptosisthem.

 

Every wound is an open gateway for bacteria to enter the body and attack the living tissues.

The cells natural defense system, or what we call an immune system, is triggered in response to the onslaught. If the microbial colony can invade the tissue and reach a critical mass, an infection has become reality. A number of treatments has been developed to prevent the infection from occurring and spreading in the body beyond control, including from simple procedures like cleaning and airing the wound to highly sophisticated systemic methods, like the use of antibiotics. The only certain way to prevent the wound from infecting, is to let it close and heal completely. As long as the wound is open, the bacteria can, and will, attack through it.

Some surgical wounds are by nature such that they are not allowed to close via natural course. For example, long term catheter wounds remain open because the tube inserted through the skin keep the tissue from closing, until the catheter is removed. Dental implant abutment is clinically speaking nearly an equivalent situation. The purpose of the abutment surface is to create a sustainable biological seal between oral cavity and the rest of the body. In the ideal situation the gingival tissue will heal and create an intimate contact with the abutment surface of sufficient width able to widthstand the continuous bacterial attack. The weak point in the system is the lack of attachment between the material surface and cells.

MetAlive® surface modification has for the first time created a bond between living cells and inorganic materials, metals and ceramics.

MetAlive® solves the problem of wound healing

Clinical implications of using MetAlive® surface modification 

 Wound healing process is the natures way of dealing with the trauma of implantation. Clinically, the advantages provided by MetAlive® surfaces improved wound healing are manifested in many ways. Some clinical effects have already been proven in clinical studies, such as faster healing, less bone resorption under the attached gingival tissue, smaller sulcus and greater biological width. These effects were observed in dental implant abutment study and in a skin penetrating implant study.

It is expected that many other clinical benefits of MetAlive® are still uncovered, even though for some of which, there exists already indicative evidence. Reduction of infections is one of the most prominent effects to be studied in the next clincal trial.

How does MetAlive® work

In the following are listed the main, observable differences at ultrahistological, histological, clinical and mechanical level. In short, MetAlive function can be summarised by stating that MetAlive® enhances wound healing by allowing cells to attach onto itself and therby improving the healing process steps at every level and timespan. 

This chain of clinical events can be simplified to consist of:

clinical scheme

Comparison between traditional and MetAlive dental implant abutments

Time 

MetAlive 

Ordinary titanium 

Immidiately after implantation

Specific protein adsorption

Non specific protein adsorption

0-3 days

 

Cell attachment, faster spreading and proliferation, low inflammatory response, loose connective tissue with round cells at the interface.

Poor attachment, slow spreading and proliferation, moderate inflammatory response, loose connective tissue with densely packed flat fibrous tissue around the material.

3-11 days 

Cell and tissue attachment on MetAlive. No encapsulation.

No attachment of tissue. Encapsulation with dense fibrous tissue layer. 

11 days – 12 weeks

 

Measurable mechanical attachment of tissue on MetAlive. Histologically higher level of tissue contact. Clinically faster healing. Significantly reduced bone resorption during healing. Smaller depth of sulcus.

 Thin tissue remnants obwervable on removed healing abutments. 

No attachment. No tissue remnants observable on removed abutments.

 

Beyond 12 weeks

 

New attachment on permanent abutment with MetAlive.

 Histologically greater biological width or amount of contact between the abutment and the tissue. 

No attachment 



Healing phases

MetAlive 

Ordinary titanium

Blood clotting

Selective proteins are adsorbed onto MetAlive surface from the blood. This happens within seconds after the implantation action. The nanotexture of MetAlive offers specific binding sites for the proteins.

Proteins also adsorp on the traditional polished surfaces which however have no binding sites to offer, nor are selectively adsorbed.Tissues natural inflammatory defence mechanisms take action agains bacteria and debris. 

Inflammatory

Inflammatory cells also identify if the foreign body present is friendly or hostile. MetAliveÒ surface is considered a friendly material as it is made of pure titanium oxide, the most biocompatible synthetic material on earth, and it has the extra advantage of having the adsorbed protein layer on it. 

Titanium, its alloys and Zirconium ceramics as such are highly biocompatible materials. The lack of attachment however leaves the cells experiencin. 

Proliferative

Cells begin to proliferate directly onto the MetAliveÒ surface, which has binding proteins attached to it. In cell culture studies fibroblasts and epithelial cells spread and attach faster to MetAliveÒ surface than to ordinary polished titanium material. This process begins within minutes from the implantation action.(REF) An intact, thin, new fibrous tissue layer is formed creating the next level of defence against microbial attacks. In other words, MetAliveÒ helps the cells to close the wound and prevent further attack by microbes. Within three days a markedly improved wound healing has occurred. (REF)

Cells are not able to spread and attach to ordinary abutmen surfaces properly. Thus the blood clot is replaced by new intact tissue slower and the inflammatory reaction remains stronger. The movement between the abutment surface and the cells further irritate the tissue and increase the inflammatory and foreign body reaction against the abutment. Tissues are not in proper contact with the abutment, the gap stays open and microbes have an open passageway to the wound. The tissues react by starting to form a dense fibrous encapsulation against the foreign body present.

Remodeling

At this point MetAliveÒ offers a continuous improved attachment for the connective tissue and epithelium. Significantly reduced bone resorption and increased contact surface area together with a mechanically measurable attachment level keep the gingival tissue healthy and biological width at its maximum level.

With the help of chlorhexidine, proper cleaning and continuous monitoring for most abutments all goes well and the tissue wins the battle against microbia, regardless of the surface that does not achieve proper closure. With any luck, the abutment has now healed without any complications.

In long term however 10-40% of all implants are reported to develop peri-implantitis and other complications.

 

 

MetAlive® - bioactive nanonotechnology

2 millimeters             2millimeters

MetAlive® surface improves the spreading of cells over the surface of the abutment. Each light point on the two pictures is in fact a single cell seen under the fluorescent light microscope. MetAlive® surface on the left shows a much more rapid and even spreading of cells over the entire surface than the ordinary medical grade titanium, where the cells have not spread anywhere from the seeded area (on the right picture).

 

 

 
0,1 mm                      01 mm 

(0,1 mm = 100 micrometers)

Right after the implantation the cells have come to contact with MetAlive® surface and will start dividing, spreading and covering the complete surface of the abutment. This image shows how individual cells have formed a continuous layer of cells on MetAlive® surface after just 1 day after seeding. In other words the beginnings of intact healed tissue have been formed.

 

 0,07 mm                   007 mm

(0,07 mm = 70 micrometers)

Cellular structures on MetAlive®surface seen under scanning electron microscope at a magnification of 5000x. Each cell sits on the surface and is    connected via tenticles and other organels to it, which forms the basis for closing the wound at the abutment interface. The length bar at the top of the picture is approximately equal to the size of a single cell. The sample is from an animal experiment in subcutaneous tissue. Even after removal of the sample from the tissue, cells remain in abundant quantity on the surface of the implant.

 

0,05 mm                   005 mm 

(0,05 mm = 50 micrometers)

Scanning electron microscopic images showing how cells can sit on the MetAlive surface, spread and flatten on it at different stages of a wound healing process. This process is faster and more widespread on Neoption surface than on other medically used materials.

 

0,002 mm                 0002 mm

(0,002mm = 2 micrometers)

This is a transmission electron microscopic image of the internal structure of a single human skin cell, called fibroblast, sitting on MetAlive® surface (black material on top). The thin lines right next to the MetAlive® surface are cell membranes. This type of close contact with attachment mechanisms visible can only be seen with MetAlive® while other abutment materials are not attached with the cells, leading to a clear gap between the two. The magnification of the image is showing an area of some 10 square micrometers which is equivalent to about 1/100.000 of mm2.

0,00002 mm                000002 mm

(0,00002mm = 29 nanometers)

MetAlive® surface seen under Atomic Force Microscopy. The unique patented nanotopography of MetAlive® improves the protein adsorbtion from tissue fluids in seconds after the implantation has taken place. This difference leads to cells ability to recognise MetAlive® surface as a friendly surface and come into intimate contact with it. The drawn image represent a protein sitting on the pores on MetAlive® surface. The magnification of this image is showing an area of approximately 2 square micrometers which is equivalent to 1/500.000 of a mm2.