Thanks to advances in medicine, people today live longer than ever. Understandably, we also want to remain healthy and mobile well into old age. Implants and prosthetics can replace worn joints and teeth, relieve pain and greatly improve our quality of life. Modern medical implants are small marvels of biomaterials science and bioengineering. Yet, despite their sophistication, implants do occasionally fail, which can have serious consequences for patients.

Why do these failures occur – and why have they been occurring more frequently in recent years? Empa researcher Martina Cihova from the Joining Technology and Corrosion laboratory aims to find out. To do so, she is taking a close look at the behavior of implants inside the body. The scientist has received a four-year Ambizione Grant from the Swiss National Science Foundation for her research project.

Many commonly used implants – including artificial joints, dental implants and pacemakers – are made of titanium. This transition metal is lightweight and strong, highly durable inside the body, and particularly good in allowing bone tissue to attach to it. These favorable properties are due to a thin oxide layer that forms naturally on the surface of titanium when exposed to air. Ultimately, it is not the titanium itself, but this protective surface layer that comes into contact with the body. “As this native passive layer is less than ten nanometers thick, it often receives too little attention in medical technology and research,” says Martina Cihova.

In addition, some manufacturers modify the oxide layer, for example, by thickening it to color-code implant types and sizes. Others roughen the surface of the implants to encourage bone integration – or laser-engrave the serial number to ensure traceability. Thanks to laser-based processes, even 3D printing of patient-specific implants is now possible. These are all useful applications, but: “Any treatment can change the titanium oxides on the implant surface,” says Cihova, “and there has been far too little research into how these changes affect the interaction of the implant with the body and its corrosion resistance.”

With her project, the Empa researcher aims to close this knowledge gap. Her fascination with materials science began during her studies in bioengineering, which inspired her to shift focus and pursue a PhD in metallurgy to dive deeper into the world of materials. Today, she combines both fields of expertise, focusing on where metal, or metal oxides, and biology meet: the interface between implants and the human body.

“Such biointerfaces are incredibly complex, but also extremely fascinating,” says the young researcher. “When we think of corrosion, we usually think of salty seawater, humid air, maybe a rusty bicycle – but not the human body.” Yet our body can be a surprisingly aggressive environment to materials, especially when immune reactions take place. Immune cells release various substances that can, for instance, lower the pH value and attack the implant. So, what effect does the body's environment have on materials that we consider stable? This is the question at heart of biocorrosion research.

These processes are very complex on both the (electro)chemical and the biological level. In addition, not all titanium oxide is the same. Although its chemical composition, TiO2, remains the same, titanium oxide can exist in three different crystalline forms or in an amorphous, “undefined” structural state. Each of these forms has different electronic and electrochemical properties, which may also affect how the material interacts with the body.

The surface treatment of implants can alter the crystalline structure of these oxides, either across the entire implant or only in selected areas. To understand how this local heterogeneity affects the already complex biointerface, Cihova and her team are taking a systematic step-by-step approach. In collaboration with experts for laser processing of metals at Empa in Thun, they create sample substrates with differently structured titanium oxide layers that vary systematically in their heterogeneity. These substrates are then exposed to increasingly complex body fluids to investigate the fundamental relationships between oxide structure, properties and reactivity.

“We start with simulated physiological fluids that contain only water and ions,” explains Cihova. The next step involves adding proteins such as fibrinogen, which is involved in immune responses and wound healing. Finally, the researchers plan to investigate how the biointerface behaves in contact with living macrophage cells – the body's police force. For this, they are collaborating with Empa researchers in St. Gallen. "I am very pleased that we were able to get colleagues from all three Empa sites on board for this project," says Cihova. "The complex questions we are addressing are inherently interdisciplinary, and tackling them requires expertise from across multiple fields."

Optimized therapy instead of unnecessary surgery: The shoulder joint is particularly mobile and equally complex. 4D X-ray analyses should now improve the diagnosis of joint problems. Image: Empa

Shoulder instabilities, for example, are difficult to diagnose as they usually only occur when the shoulder joint is in motion. A time-resolved 3D analysis now makes it possible for the first time to precisely capture these dynamics. Empa researcher Ameet Aiyangar combines X-ray videos with virtual 3D models of the joints to detect these instabilities with millimeter precision.