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Titanium screws and stem cells for dental implants

How are we supposed to chew and smile when the tooth fairy comes to fetch our second set of teeth? When it’s difficult to tell the difference between modern tooth implants and real teeth in both technical and aesthetical terms, people who lose their teeth due to accidents or age very quickly regain their smile. However, there needs to be enough bone to hold and support the implant. Prof. Dr. Dr. Ralf Gutwald and his team in the Department of Oral and Maxillofacial Surgery at the Freiburg University Medical Centre have developed several methods of bone regeneration that involve bone replacement materials as well as stem cells.

The X-ray image shows the jawbone with titanium screws on which artificial teeth have been mounted. © Prof. Dr. Dr. Ralf Gutwald

Does our smile reveal a perfect row of white teeth? The state of our teeth reveals our oral hygiene habits; however, we are powerless to prevent the loss of teeth as a result of accidents or age. Modern dental implants can replace missing teeth to the extent that even a completely toothless jaw can be restored with artificial teeth. Artificial teeth can tolerate the same loading from chewing as natural teeth and they can also look and feel similar to natural teeth. However, for a dental implant procedure to work, the prosthesis needs to be firmly anchored in the jawbone. Biocompatible and corrosion-resistant titanium screws are used to fix dental implants in place in the jawbone, which requires enough bone to be present. What can a dental surgeon do when the bone has degenerated, for example due to the lack of loading? “Before we insert an implant, we frequently need to increase the amount of bone in a patient’s jaw,” said Prof. Dr. Dr. Ralf Gutwald, senior physician in the Department of Oral and Maxillofacial Surgery at the School of Dentistry at the University of Freiburg.

Can bone tissue be grown in vitro?

One of the methods used to prepare a jawbone for a dental implant is known as sinus lift: the dental surgeon makes an incision in the patient’s gum on the cheek side of the upper jaw, thereby exposing the bone where the implant is to be placed. The exposed bone is cut in such a way as to create a hollow space into which bone-graft material is then packed. But how is it possible to increase the quantity of bone? By using different bone-graft materials. One possibility is to harvest bone from another location in the patient’s mouth and another is to use bone from the hip, thus creating enough new bone to accommodate the implant. However, many patients who undergo this type of surgery complain about complications arising at the site where the bone-graft material is harvested. Time is another crucial factor. The bone graft tends to degenerate rapidly during the time it takes the wound to heal, usually around three months, which has the effect of reducing the quantity of bone available to accommodate the implant. In order to counteract this, an alternative approach involves either blending the patient’s bone with bone replacement material, or simply using bone replacement material on its own. Such materials can be prepared from powder extracted from animal bone, which then forms a pore matrix into which new bone tissue can grow. However, this process takes up to six months. Both of the two aforementioned methods are too time-consuming and the bone substance does not reach the required density and volume. “This is why we considered cultivating bone tissue in vitro. We first had the idea around ten years ago,” said Gutwald. Surgeons initially remove a small amount of bone tissue from the patient requiring a dental implant. The bone tissue is placed into a Petri dish where osteoblasts, i.e. bone-producing cells, develop. After around eight weeks, the tissue can be inserted into the jawbone where it integrates and becomes bone. This method has since been licensed to the Freiburg-based company BioTissue Technologies AG. It is still frequently used, but no longer regarded as state-of-the-art. “We have found out that this construct does not completely develop into bone, thus leaving us with insufficient bone-graft material,” said Gutwald. “The ideal situation is when patients still have enough of their own jawbone. However, patients with reduced quantities of jawbone can now benefit from an idea Gutwald and his team came up with a few years ago: using the patient’s own stem cells to generate new bone.

Using a patient’s own stem cells for the regeneration of jawbone

Over the last five years, the Freiburg researchers have carried out clinical studies in cooperation with the university hospitals in Mainz and Groningen to test the efficiency of this state-of-the-art stem cell method. Gutwald and his team came up with the possibility of using a patient’s own stem cells for the regeneration of jawbone during an experiment involving the evaluation of the effect of a specific molecular growth factor on the in vitro growth of osteoblasts. This growth factor, which is known as bone morphogenetic protein (BMP), induces stem cells to differentiate into osteoblasts and produce bone substance. When BMP is injected into muscles, it attracts stem cells and induces them to differentiate into bone – de novo bone generation so to speak. BMP does the same in a Petri dish as it does in a jawbone: Gutwald and his team found that the addition of BMP led to the rapid generation of bone that was of much greater density and volume than bone generated with other methods. However, BMP has still not been approved in Germany for the production of dental implants. This is why around five years ago dental surgeons decided to do things the opposite way round: “We thought that if we were not allowed to use BMP to attract stem cells to the desired location in the jawbone, then the only option was to bring stem cells into the jawbone,” said Gutwald.

The method devised by Gutwald and his team is now well established and has many advantages. The procedure is as follows: the operating surgeon removes a small amount of stem cell-containing bone marrow from the hip. The stem cells are isolated by centrifuging the bone marrow and subsequently mixed with bone replacement material, which forms a pore matrix for the stem cells to optimally differentiate into osteoblasts. The mixture can be implanted “chair-side”, which means that it is not necessary to wait the eight weeks that it takes to culture osteoblasts in vitro. Bone forms directly in the patient’s body, completely de novo. The results are fairly promising: in contrast to in vitro bone cultivation, the use of stem cells leads to a much larger quantity of bone, which is also denser. Around 30% of new bone usually develops in a patient’s jaw within around four months. In addition, the newly generated bone adapts far more organically into the surrounding tissue. The stem cells are even able to grow new blood vessels, which considerably optimizes the supply of the tissue with nutrients.

Two histological pictures next to each other; the picture on the left contains a larger number of blue and red tissue structures than the one on the right.
The histological pictures of the jaw show that stem cell therapy combined with bone replacement tissue (left) leads to the generation of larger quantities of bone (red) than is possible using osteoblasts that have been grown in culture dishes (right). © Prof. Dr. Dr. Ralf Gutwald

The use of stem cells in combination with bone replacement material has now become the most frequently used method at the Dental Hospital in Freiburg for treating patients with insufficient amounts of jawbone. Gutwald’s team is already working on applying their method to the lower jaw, and it has already been tested for leg and vertebral body surgery. One of Gutwald’s staff is currently visiting all the German dental hospitals to present the stem cell-based method. The method has already become fairly popular and it can be safely assumed that it will soon become the gold standard in dental implant surgery in Germany.

Further information:

Prof. Dr. Dr. Ralf Gutwald
Department of Oral and Maxillofacial Surgery
Freiburg University Medical Centre
Hugstetterstr. 55
D-79106 Freiburg
Tel.: +49 (0)761/ 270 - 47 010
Fax: +49 (0)761/ 270 - 48 000
E-mail: ralf.gutwald(at)uniklinik-freiburg.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/titanium-screws-and-stem-cells-for-dental-implants