Nowadays, implant surgery is commonly performed as a standard procedure; however, there are still potential risks associated with impaired wound healing. Such complications could pose challenges during treatment and adversely impact the patient's overall recovery process. To overcome this problem, researchers are looking at ways to improve implant integration and reduce the risk of infection.
Curious to learn more about this field of research and how QSense QCM-D analysis is used to advance understanding, I reached out to Hanna Tiainen, associate professor at the Department of Biomaterials, University of Oslo. Prof Tiainen’s research focus is on biomaterial coatings and how they affect the biological response of living tissue. In her team, they are particularly interested in how to tackle inflammation and bacterial infections on implant surfaces using plant polyphenols. Recently, they conducted a study1 to examine how these coatings influence protein adsorption and modulate cell behaviour on the surfaces of implants. In this post, I share what I learned from the interview with Prof. Tiainen.
Impaired wound healing around implants can cause problems for the patient
Although placing implants to restore function or aesthetics has become a commonplace surgical procedure, impaired wound healing around implants can cause a lot of trouble for the patient, Prof. Tiainen says. Poor integration of the implant in the surrounding tissues often results in persistent infections that are notoriously difficult to treat and typically leave removal of the infected implant as the only effective treatment option.
The challenge of designing a surface that does not trigger the immune system
Poor implant integration is often connected to how the body reacts to the implant as a foreign body. Prof. Tiainen explains. This so-called foreign body reaction that is initiated by our immune system is unique to every material and depends on how biomolecules adsorb on the surface of the implanted material. This process is very similar to how our immune system flags bacteria and viruses with antigens for immune cells to neutralise and get rid of them. The challenge is to create a surface that is not triggering the immune system to fight against it and does not cause inflammation and encapsulation of the implant, Prof. Tiainen says.
Developing biomaterials that reduce the risk of infection
The response of the immune system is highly dependent on how cells ‘see’ the surface of the implant material, Prof. Tiainen continues. This is mostly defined by the initial adsorption of biomolecules. If we understand the underlying adsorption mechanisms on a particular surface, we could attempt to orchestrate the adsorption process to favour specific proteins over others or change their conformation to display or hide important receptor areas that influence wound healing and the acceptance of an implant within your body, Prof. Tiainen says.
Our research focuses on understanding how the physical and chemical surface properties of material govern the biological response towards biomaterials that are in direct contact with living tissues, Prof. Tiainen says. A lot of our current research efforts focus on developing multifunctional biomaterials and surfaces that improve tissue integration and reduce the risk of infection, especially in situation where natural wound healing around the implanted biomaterial may be hampered for example by underlying chronic inflammatory diseases or cancer treatments.
This specific study1 was part of a research project funded by the Research Council of Norway in which we focus on tackling inflammation and bacterial infections on implant surfaces using plant polyphenols, a group of antioxidant and antibacterial compounds that are found in several plant-based foods. We are particularly interested in understanding how these polyphenolic coatings change the way proteins adsorb and alter cell behaviour on implant surfaces, so we are keeping our QSense E4 very busy with this project, Prof. Tiainen says.
Analysis to understand the foreign body reaction towards a coated implant surface
In our published study,1 we investigated how the foreign body reaction towards titanium implants alters when we modify their surface with antioxidant polyphenolic molecules, Prof. Tiainen says. The overall effect of the interaction of the immune system and soft tissue can be studied with blood and cell cultures. By studying coagulation and complement activation markers in blood that has been in contact with the modified implant material, we can compare the response to an unmodified control surface. Similarly, in vitro cell studies can answer whether the modification exerts any unwanted effect on cells that are involved in wound healing. However, neither method can directly answer why cells react to the material surface the way they do. Therefore, we needed another method that tells us more about how biomolecules adsorb on the surface and define further interactions with cells in the surrounding environment, Prof. Tiainen explains.
Understanding why cells react to the material surface the way they do
QCM-D allowed us to probe how the surface modification with polyphenolic molecules alters protein adsorption compared to our titanium control surface, Prof. Tiainen says. We were particularly interested in seeing how firmly proteins bind to the surface and whether they can be replaced by adsorption of other proteins that have a higher affinity to the surface. This remodelling process is typically known as the Vroman effect in literature. The QCM-D results we obtained also allowed us to make assumptions regarding the conformation of the adsorbed proteins based on their characteristic adsorption behaviour and layer properties.
Using QSense QCM-D analysis to characterize protein interaction with a functional implant coating
The QCM-D technology was particularly helpful for gaining insight into the interaction of the proteins with the polyphenolic layer in liquid environment in real-time, Prof Tiainen says.
In brief, the experiments were executed as follows:
A few nanometres thin polyphenolic film was deposited directly on a titanium sensor mounted in our QSense E4 instrument before a solution containing proteins was introduced.
Between coating deposition and studying the adsorption of biomolecules, the sensor was thoroughly flushed with buffer solution until a stable baseline could be recorded.
After monitoring the adsorption of proteins, we checked how much of the adsorbed molecules were desorbed during rinsing the sensor with buffer solution.
The QCM-D measurements revealed that a higher amount of proteins adhere to the polyphenolic surface modifications compared to unmodified titanium. In particular, the advanced modelling capability of the QSense DFind analysis software allowed us to find differences in the viscoelastic behaviour of the protein layers, indicating changes in the structure of the adsorbed protein pellicle on our modified titanium surfaces.
A key result of the QCM-D analysis was that the implant surfaces modified with polyphenolic molecules showed release of antioxidant polyphenolic molecules that protected adherent cells against oxidative stress, while changes in the adsorption of blood plasma proteins on the modified surfaces resulted in slightly reduced complement activation in blood, Prof. Tiainen says.
Outcome - an approach to dampen the immune reaction towards implant materials and reduce the risk of impaired wound healing
Surface modifications are a potent tool to influence the complex cascade of biological interactions that occur when a material comes in contact with living tissues in the body, Prof. Tiainen says. In this study,1 we saw that polyphenolic coatings alter the adsorbed protein layer and reduce the innate immune response towards titanium, which itself is a highly biocompatible material that typically induces low foreign body reaction when implanted in the body. Since we can deposit a thin layer of polyphenolic molecules on the surface of virtually any material, we could use our surface modification method to dampen the initial immune reaction towards implant materials that are known for causing a much stronger foreign body reaction than titanium, Prof. Tiainen concludes.
Weber, F., et al., J. Biomed. Mater. Res. A, 2022, 110(7):1341-1355
Malin graduated in engineering physics in 2006, where her research focused on the QCM-D technology. Since then, she has been scrutinizing the how’s and why’s of the world in general, and the world of QCM-D in particular.