Until now, doctors had to rely on X-ray images and CT scans to obtain occasional snapshots of the fracture site. Ganse and his team have published their findings in the journals "Biosensors and Bioelectronics" and "Journal of Functional Biomaterials.".
Imagine taking a small device out of your pocket, placing it on the skin over the fractured area, and, in a matter of seconds, knowing how the fracture is healing. If a cast has been applied, there would be a small opening to allow contact with the skin. This intriguing idea could soon become part of standard postoperative monitoring worldwide. The new method allows for precise monitoring of blood flow and oxygen levels in the blood of the fractured tissue without the need for harmful short-wavelength radiation. “Commercially available devices for examining blood flow and oxygen saturation in the skin and muscles use non-harmful LED and laser light, bright enough to penetrate to the underlying bone tissue,” explains Bergita Ganse. In collaboration with her team at Saarland University, Ganse has discovered that these devices can also be used to monitor the healing process of bone fractures. The team recently demonstrated the success of this approach by applying the methodology to a study of patients with tibial fractures.
“Our method is not intended to replace X-rays. We consider it a useful complement, a rapid monitoring method that provides additional information in areas where existing techniques have gaps,” explains Bergita Ganse, holder of the Werner Siemens Foundation Endowed Professorship in Innovative Implant Development at the Saarland University Medical Campus in Homburg. Until now, bone fractures were monitored using X-rays or CT scans, which exposed the patient to high-energy radiation, something that cannot be repeated too frequently. “Another drawback of using X-rays and CT scans is their delayed detection of early healing activity in bones.” As a fracture heals, soft bone tissue forms in the fracture area, but the bone density is not yet high enough to be detected by X-rays. Increased bone density occurs when calcium salts are deposited at the fracture site (mineralization), but this only happens at a later stage of the healing process,” explains trauma surgeon and physiologist Bergita Ganse. Before mineralization occurs, the healing process is virtually invisible, making it difficult to determine whether the fracture is healing properly. “CT scans and X-rays only provide snapshots, but what happens between two scans or two images is largely invisible,” says Ganse.
The new technique developed in Saarland allows for continuous, non-invasive monitoring of bone healing directly through the skin. As a result, patients gain a better understanding of how the healing process is progressing. This additional monitoring of the fracture site allows for earlier detection of potential complications. “We know from studying lower leg fractures that complications arise in 14 out of every 100 cases, but they are often only detected at an advanced stage,” explains Professor Ganse. “The sooner we detect that something isn’t progressing as it should, the sooner we can intervene, and early intervention can significantly improve outcomes for the patient. We have a whole range of tools for targeted corrective treatment, such as pulsed ultrasound, shockwave therapy, and magnetic field therapy,” says Ganse. Sometimes the problem is mechanical: “There may simply be too much movement in the fracture area, which can disrupt the repair process and require better fixation.”
Professor Ganse sees great potential in the dissemination of this monitoring technology: "Small and affordable monitoring devices could improve the treatment of fractures in settings that do not have access to large and expensive equipment, such as X-ray machines, especially in resource-poor countries or remote areas."
Fracture repair is a complex process consisting of several phases. Bergita Ganse explains the bone regeneration process: “Initially, a thin connective tissue structure made of fibrous tissue begins to bind the fracture. Over time, new bone tissue forms and is gradually supplied with blood as new blood vessels develop.” The team at Saarland University has studied the details of the fracture healing process and measured how blood flow and oxygen saturation change as bone repair progresses. In two separate studies, Ganse and her doctoral students Oana Scholz and Cedric Nowicki monitored the healing process in 55 patients with tibial fractures over several months and compared their data with a control group of 51 healthy individuals. The results were striking: “Blood flow and oxygen saturation follow a very characteristic pattern during bone regeneration,” says Ganse. This is the first time such detailed observations of the fracture healing process have been made in human patients.
“Initially, blood flow increases sharply and reaches a peak. After about two or three weeks, the levels begin to decline again.” Oxygen saturation in the tissue surrounding the fracture site also follows a characteristic pattern: it initially drops to a minimum before rising again after two or three weeks, when new blood vessels begin to form. “We can monitor both processes with relatively simple, non-invasive measurements,” explains Professor Ganse. “We use a commercially available device that combines laser Doppler technology to monitor blood flow with white light spectroscopy to detect oxygen saturation in the tissue. If the values don’t return to normal after a few weeks, it’s usually an early sign that something isn’t progressing as it should.”.
The team's initial results suggest that blood flow patterns and oxygen saturation vary depending on the underlying cause of delayed healing. "Since we've only seen a few cases where the fracture hasn't healed so far, further research is needed before we can draw definitive conclusions about these differences," says Bergita Ganse. There are many reasons why a fracture might not heal properly. "The patient may have moved too much and not sufficiently immobilized the fractured limb, or there may be associated risk factors, such as smoking or cancer, that hinder healing," explains Ganse. "With X-rays, these problems only become visible at a relatively late stage. But our method seems able to detect them earlier." However, a current limitation of the light-based monitoring method is the depth of measurement. "At the moment, we can't probe fractures that are more than five centimeters below the skin," explains Bergita Ganse.
Ganse's team is also working on other innovative ways to monitor the healing of bone fractures, such as using self-sensitive shape-memory materials that can provide data on changes in stiffness and elasticity at the fracture site as the bone heals.
The research is part of the "Smart Implants" project, coordinated by Professor Ganse and funded with €8 million by the Werner Siemens Foundation. The five-year-long project involves interdisciplinary collaboration between research groups at Saarland University working in the fields of medicine, engineering, and computer science. The teams have already developed several prototypes and patents for smart fracture plates. These customized implants are designed not only to monitor healing from the moment of surgery but also to actively promote it, for example, by providing micromechanical stimulation to the fracture site or dynamically adjusting the implant's stiffness. Data from the new research on monitoring using laser Doppler spectroscopy and white light are now being integrated into the next generation of these smart implants. Currently, the teams are working on miniaturizing the technology so that it can be incorporated into intramedullary nails, which are only a few millimeters wide. Additional EU funding has been obtained under the Horizon Europe programme, as part of the SmILE (Smart Implants for Life Enrichment) research project.
Ganse and her team are now looking to expand beyond tibial fractures and are working to apply their new method to other types of fractures and bone defects. “I’m excited to see how quickly this technology will find application in both research and routine clinical care,” says Professor Ganse, who brings a unique perspective thanks to her experience in space medicine. Ganse collaborates with the European Space Agency (ESA), the German Aerospace Center (DLR), and NASA in the United States, where she studies, among other things, how bones and muscles degrade in space. Her research has contributed to the development of training programs that help astronauts counteract this type of musculoskeletal degeneration during long-duration missions.
