Minh Khai Le Thieu has studied using a synthetic scaffold to promote bone growth after tooth loss in his doctoral thesis. Perhaps this could contribute to the use of a new type of biomaterial? Today, animal bone is widely used to promote bone growth around implants.
Ph.d. graduate Minh Khai Le Thieu in The Oral Research Lab. Foto: Marie Lindeman Johansen, OD/UiO
- When a tooth is lost, the supporting tissue surrounding the tooth also shrinks. To place an implant in the jawbone, we often need to increase the bone volume to make the area around the implant more stable, says Minh Khai Le Thieu.
- You can harvest the patient's bone to insert, but this requires an additional procedure and a limited amount of bone can be harvested. Alternatives include using bone from other humans or animals, but this requires thorough pretreatment of the material. Animal bone is often used today, but it is desirable to replace this with synthetic materials.
- I have looked at titanium dioxide (TiO2) scaffolds developed at The Oral Research Lab at The Faculty of Dentistry. There has been considerable research on titanium dioxide scaffolds, which is valuable to continue building upon, Minh says.
Titanium dioxide scaffolds
Can you describe what you have done?
- These are studies in clinically relevant and more difficult preclinical models than previously conducted. We have previously looked at using the material in extraction sockets/alveolar bone right after tooth extraction. Extraction sockets are the cavities in the jawbone after a tooth is pulled. In those cases, we know that bone grows regardless, because the conditions are favorable, Minh explains.
- We used two models in the study: We tried to build on bone after tooth extraction that had already healed, meaning the bone volume was reduced. We also used the scaffold around implants to simulate cases where bone is missing after the implant is placed.
- The purpose was for the scaffold to hold space for new bone to grow into it, both when bone is missing after tooth extraction and in cases where bone is missing around an existing implant, Minh explains.
Creating a foundation for bone growth
What findings did you make?
- As shown previously, the bone readily grows into the scaffold, and new bone grows on the materials. Bone grows into the scaffold, but it doesn't grow much more compared to the control groups we have compared with. There was also less bone growth compared to the negative control group, where no materials were used. This may be explained by the fact that the bone must grow around a material instead of having a free path. However, it doesn't grow more bone than comparable materials used today. Today, we often use bone from animals. Titanium dioxide scaffolds are synthetic, so there is potential here to replace animal materials with artificial materials, says Minh.
Were you satisfied with the results?
- The initial results showed a limited amount of new bone, so we investigated whether there is potential for further bone growth. We have only studied the material for twelve weeks, but we wanted to check if there were indications that more bone could grow later. We performed immunohistochemistry, i.e., we took tissue sections of the scaffold, which indicated that there might be potential for further growth. The results suggest slower growth with both bovine bone and our material, so there is a chance that more bone might grow over time. If we had waited longer than the twelve weeks the experiment lasted, there might have been more bone growth.
Ceramic is a hard and porous material
What materials did you test?
- The titanium dioxide scaffold is a synthetic
ceramic material. It is made quite simply in the lab by taking titanium dioxide powder and water to create a solution which we use to coat a foam plate. The foam plate is then heated so that the foam burns away, and the powder hardens into a ceramic. Titanium dioxide powder and water are burned like clay, and in that process, it hardens into a solid substance, a ceramic, a hard material. It is meant to hold the place where the tooth was so that bone can grow into the scaffold, Minh explains.
- The ceramic is as strong as bone and quite porous, so there's space for the bone to grow into the scaffold. The process is fundamentally simple, and synthetic materials can be produced on a large scale, unlike using bone tissue from animal products, which is largely done today.
- In the clinic, we usually use bovine bone for the same purpose as scaffolds. It is the same type of material but with a different origin. We wish to cut the use of animal products, so it would be good if a synthetic material could replace it, says Minh.
- The findings are positive, and we also see in these models that the scaffold retains its shape. It creates space that could be filled with bone. The idea is for new bone to grow into the scaffold so that it becomes part of the jawbone. The purpose is for it to integrate into the bone. This has previously been studied at the faculty, and my studies are developed from these models, says Minh.
A new and time-saving method in immunohistochemistry
- The fact that the material is a ceramic posed challenges regarding lab testing. To perform immunohistochemistry, we had to use a different method than usual. We used a newer method in immunohistochemistry developed at the University of Giessen in Germany. Immunohistochemistry is an immunological technique used on tissue sections, and we wanted to look for markers that could indicate the potential for further bone growth.
- Typically, when staining markers in immunohistochemistry, you need to pre-treat large tissue blocks. You then cut the large tissue blocks with a microtome into thin sections, which we couldn't do in this case since we had a ceramic scaffold that was too hard for regular cutting. If everything else is soft and it is hard, we wouldn't be able to cut it.
- With the new method, first, we fix the tissue sample and then embed it in plastic so that everything is hard. Then we can cut the blocks into thin sections. Once we have these sections, we can remove the plastic from each section individually, which is faster than removing the plastic from the entire block. Instead of spending half a year decalcifying a block, we spend a couple of days on the process. It's a significant time-saver.
- We could also use this method in standard histology. This way, we could obtain many more sections from a sample compared to cutting thick slices that are ground down to the desired thickness, which is the usual method previously used for implants and scaffolds. When cutting a fairly thick slice, we lose quite a bit of the tissue we need to test. As a result, we get significantly less data from the same type of sample than we get with the new method. The result of this new method is that we get much more information from the same amount of tissue samples.
- It is a method that, as far as we know, has not been used much in dentistry, says Minh.
Opportunities for further exploration?
What is the significance of the work you have done - what are its benefits?
- The tissue sections from the immunohistochemistry showed that there is potential for more bone to grow into the scaffold. This indicates that the material has potential.
- Maybe it can be modified by adding substances that promote bone growth because now, the bone only grows from the original bone and outward. Perhaps we could get bone to grow from the inside of the ceramic and outward? That would be even better.
- It is possible to explore this further, or perhaps other models may be more suitable. Maybe we could test whether it can maintain the space after a tooth is lost, so it doesn't close up after tooth extraction. The opportunities pertain to the development of the material and are suitable for both laboratory work and clinical studies, concludes Minh.
