Every year, millions of people around the world receive medical implants as a treatment. In most patients, the function of damaged tissues or organs is successfully restored, but in some patients, complications occur, such as pain due to excessive fibrosis. RIVM invests in the improvement of the current safety testing strategies.
Before an implant reaches the clinic, it is thoroughly tested for safety. This is mainly done in tests based on the chemical nature of the material. More recently, it has become clear that mechanical forces also have a significant role in the host response. That is why RIVM is developing new testing strategies by including these mechanical forces, resembling the interface between the biomaterial and the patient better and in an animal-free manner.
Short video about RIVM's activities researching in vitro medical implant safety
Short video about RIVM's activities researching in vitro medical implant safety
In vitro medical implant safety
Speaker: Nick Beijer, scientific officer MedTech
NICK BEIJER: At RIVM we develop new methods to assess implant safety. We do this based on the complaints patients get and in a human relevant In vitro model.
VISUAL: In vitro medical implant safety
VOICE OVER: Every year, millions of people around the world receive medical implants as a treatment. Implants greatly differ, such as large joint replacements, silicone breast implants and mesh-materials. In most patients, the function of damaged tissues or organs is successfully restored. But in some patients, complications such as pain due to excessive fibrosis, do occur.
NICK BEIJER: Before an implant reaches the clinic, it is thoroughly tested on safety. This is mainly done in tests based on the chemical nature of the material. But more recently we have learned that also the mechanical forces play a significant role in the host response. That is why we want to update the current testing strategies by also including these mechanical forces and by this resembling the interface between the biomaterial and the patient better. And have an animal-free method to mimic the host response.
VOICE OVER: RIVM is working on two parallel lines of research to achieve this. Which involve both studying human tissues and setting up cell-based systems.
NICK BEIJER: Firstly, we want to understand what causes the adverse effects in patients. For this, we examine explanted materials from patients who developed complaints. This is a bit of the biomaterial with the surrounding tissue together and we analyse this using histopathology, transcriptomics or proteomics for example. Secondly, we have developed an in vitro model of direct cell-biomaterial interaction in which cells are exposed to chemical as well as mechanical forces at the same time. By doing this, the cells cannot only experience the chemical nature of the material but at the same time also its surface structure, its stiffness, as well as its shape and size. In this way we can assess more relevant biomaterial properties at the same time and check their influence on the host response.
VOICE OVER: By combining insights from implant-tissue histopathology with current knowledge from the literature an Adverse Outcome Pathway or AOP network will be constructed.
NICK BEIJER: We use the AOP as a guide to highlight mechanisms to be targeted in the direct-interaction in vitro model. By looking at these key events in the in the in vitro model, we will be able to describe the host response more accurately and in this way improve implant safety on the long term.
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Mechanotoxicity testing
In one line of research, RIVM examines explanted materials from patients who developed complaints to find out what caused the adverse effect. Explants consist of biomaterial and the surrounding tissue. These samples are analysed using, e.g., histopathology, transcriptomics or proteomics.
Another line of research focuses on the development of an in vitro model of direct cell-biomaterial interaction in which cells are exposed to chemicals as well as mechanical forces at the same time. This model causes cells to interact with not only the chemical nature of the material but also its surface structure, stiffness, shape and size. In this way, more relevant biomaterial properties and their influence on the host response can be studied simultaneously.
Adverse Outcome Pathways
By combining insights from implant-tissue histopathology with current knowledge from the literature, an Adverse Outcome Pathway (AOP) network will be constructed. The AOP can guide to highlight mechanisms to be targeted in the direct-interaction in vitro model. By looking at key events in the test systems, the host response can be studied more accurately towards the improvement of implant safety in the long term.
Safe-by-Design
In addition, RIVM is developing a Safe-by-Design (SbD) approach for innovative antimicrobial implants, focusing on hip implants. SbD aims to take both functionality and safety into account at an early stage of product development, thereby increasing implant safety and preventing patient complaints. To this end, RIVM develops in vitro assays that can be used in a hazard testing strategy for implants that focuses on both toxicity parameters and functional parameters such as bone integration. Finally, insights into implant properties, functionality and toxicity will be used to guide innovators on how to develop implants that are functional and safe by changing the design properties.
Projects
Currently running
Key publications
| The summary of the most important cell-biomaterial interactions that need to be considered during in vitro biocompatibility testing of bone scaffolds for tissue engineering applications. | Przekora, A. | Materials Science and Engineering: C, 97, 1036–1051 |
| Biological responses to physicochemical properties of biomaterial surface. | Rahmati, M., Silva, E. A., Reseland, J. E., A. Heyward, C., & Haugen, H. J. | Chemical Society Reviews, 49(15), 5178–5224. |
| Assessing the triad of biocompatibility, medical device functionality and biological safety. | Williams, D. F. | Medical Devices & Sensors, 4(1), e10150 |
| Future challenges in the in vitro and in vivo evaluation of biomaterial biocompatibility. | Anderson, J. M. | Regenerative Biomaterials, 3(2), 73–77 |