Being able to research various treatment options without the need to use animals or expose humans to unnecessary treatments is an important goal in medical research. In Maria Schröder's doctoral work at the Faculty of Dentistry, she developed tissue-like 3D models of oral tissues which can help to study the gum disease periodontitis.
Maria Schröder. Photo: Marie Lindeman Johansen, OD/UiO
Being able to research various treatment options without the need to use animals or expose humans to unnecessary treatments is an important goal in medical research. In Maria Schröder's doctoral work at the Faculty of Dentistry, she developed tissue-like 3D models of oral tissues which can help to study the gum disease periodontitis.
When cells in the body build or repair tissue, they grow in three dimensions (3D), making it crucial to develop models that allow human cells to grow in the same way in the lab.
"The goal of my doctoral work was to develop tissue-like 3D cell models based on cells from oral tissues, such as periodontal ligament and bone, to better understand how cells are affected by various stimuli," explains Maria Schröder.
Bioreactors and Perfusion Reactors in cell models
The 3D cell model was created using rotating bioreactors and perfusion reactors. A bioreactor is a technical device used in laboratories and industrial production for cultivating and maintaining living cells or microorganisms under controlled and optimal conditions. In a bioreactor, you can control key factors like temperature, pH value, nutrients, and oxygen content, as well as other stimulating factors such as mechanical forces. When cells rotate in the solution within the bioreactor, they bind to each other and build tissue-like structures on their own.
A perfusion reactor is a special type of bioreactor where the organ or cells being cultivated are affected by fluid flows. Such fluid flows ensure that the cells receive a continuous supply of nutrients and oxygen and that waste products are removed, similar to how blood and lymph fluid work in the body.
"In summary, we can say that both bioreactors and perfusion reactors allow us to simulate the natural environment in which cells live," explains Schröder. These models give us the opportunity to study and identify, for example, disease mechanisms and treatment effects in a more accurate and detailed way.
Periodontitis
Periodontitis manifests as an inflammation of the periodontal tissue encircling the tooth. If left unattended, the inflammation can cause the tooth to become detached from the jawbone following the destruction of the surrounding tissue and loss of bone mass, ultimately resulting in tooth mobility and loss.
"Furthermore, besides the risk of tooth loss, research indicates that periodontitis can adversely affect overall health," Maria Schröder adds.
Can you explain that further?
"Inflammation of the gums is painful for patients, and in addition to potential leading to tooth loss, it can also trigger an immune response in the body as the inflammatory signals in the gums can spread to the rest of the body through the bloodstream," explains Maria Schröder.
The purpose of the doctoral work was thus to develop tissue-like 3D models that can contribute to building knowledge about how tissues affected by periodontitis can be repaired.
"And my goal was to see if I could create conditions that allow cells to grow the way they do in the body," Maria Schröder explains.
Vitamins
There are vitamins known to affect bone growth, and vitamins D and K2 are among these. These are vitamins that patients are often recommended to take as dietary supplements. The effect these vitamins had on tissue formation was examined in the 3D models.
"Further in the work, I looked at how the cells reacted to exposure to vitamins D and K2, and whether just one of these vitamins or both together are most beneficial for the repair and growth of lost tissue," says Maria Schröder.
Alone, the two vitamins had slightly different effects. In periodontal cells, vitamin K2 affected collagen production and the structures that hold the cells together, while vitamin D increased protein factors that stimulate cells to form bone.
"In the 3D cell-based bone model, it was found that vitamin D increased the mechanical stiffness of bone-like tissue, while K2 increased the mechanical flexibility. This indicates that supplementation with both vitamin D and K2 can help strengthen the bone structure," says Schröder.
Mechanical influence
But there were also other factors studied in the models.
"When we chew food, not only the teeth but all the surrounding tissue are affected by mechanical forces," explains Maria. In addition to the vitamins, we could also study mechanical influences, such as movement and pressure, in our models. The aim was to investigate how these stimuli affected the cells and their functions.
Overall, this dissertation provides valuable insights into how laboratory models can be developed to study disease mechanisms, the effects of drugs, or how cells/tissue can be stimulated to grow. It is an important contribution to further research on periodontitis and can be used in the development of more effective treatments in the future.
