Smart Bone: from in vitro modelling of IVD damage to in vivo monitoring using implanted sensors

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Ledroit, Diane
Disser, Jérémy
Along with demographic change and age-linked conditions, low back pain and osteoporosis or related fragility fractures are overloading healthcare systems. On one hand, low back pain appears in the top five causes of disability-adjusted life year worldwide [1], reducing the ability to work and perform daily tasks. Whereas progress has been made regarding potential therapeutics that could have restorative actions targeting intervertebral discs (IVDs), such developments are impeded by the lack of an in vitro model for drug assessment, which can mimic typical motions occurring in the human body while maintaining IVD viability. On the other hand, current clinical practice for the treatment of large bone defects leading to bone regeneration are often associated with complication and lack monitoring tools. To address the need for in vitro modelling of IVD damage, we have developed a unique automated micro-physiological system (MPS) that enables six degrees of freedom (DOF) actuation on an ex vivo bovine IVD organ model in a controlled environment. This MPS efficiently transfers forces to the IVD, mimicking flexion, extension, lateral bending, torsion, tension, and compression in confined and sterile conditions. It consists of a biochamber accommodating the IVD specimen, which are preliminarily machined to fit customized sample holders [2]; fluidic ports to enable automated medium exchange; a hexapod as the actuation platform with an integrated force sensor; and software enabling the control of the entire platform. By replicating specific spine motions, this advanced MPS enables the development of complex in vitro organ degeneration models for musculoskeletal research and drug and treatment studies. This platform can also be used to generate data, providing a deeper understanding of the tissue behaviour. Aiming at improving treatment options for patients with large bone defects, the EU research project “Smart Bone Regeneration” (SBR) [3] combines smart implant with innovative tissue-engineering methods to develop a minimally invasive monitoring technique, thereby offering a valuable alternative to current clinical practices relying on autografts or allografts. While autografts provide ideal compatibility, they are often unsuitable for large bone defects, whereas allografts may face rejection by the patient's immune system. The SBR project's solution involves 3D-printed polymer components, which can be customized according to the individual patient's physiology, pathology, and gender. This adaptable framework design ensures easy implant placement and incorporates adjustable sensors for post-operative monitoring of factors such as pressure, pH value, and temperature. As a result, the smart implant can deliver crucial information regarding implant performance in terms of bone growth and infection or inflammation detection. An in vivo proof of concept will be examined in preclinical studies, demonstrating its potential as a ground-breaking innovation in the field of orthopaedics. In the long term, the SBR project holds promise as a platform technology for various bone conditions at multiple anatomical sites, including the jaw, spine, and pelvis. By enabling the use of a customizable, minimally invasive implant in isolation during fracture fixation, the SBR project seeks to revolutionize the treatment landscape for large bone defects, reducing the risk of post-operative complications, and ultimately enhancing patient outcomes and reducing healthcare costs. CSEM is an internationally recognized Swiss innovation center that develops and transfers disruptive technologies from precision manufacturing to digital technologies with a high societal impact and multiple industry applications. In CSEM Tools for Life Sciences (TLS) activities, we combine engineering skills, biological understanding, and cutting-edge infrastructure to push the boundaries of life sciences technologies. Our solutions bring together emerging micro-technologies, digitalization and the biotech/pharma industries and narrow the gap between applied sciences and industrialization. Our technologies aim at serving personalized medicine, drug discovery, preclinical drug testing, regenerative medicine, and diagnostics. [1]: GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet. 17.10.2020. [2]: Šećerović, A. et al. (2022), ACS Biomaterials Science & Engineering, 8, 3969−3976 [3]: Acknowledgement: - AO Research Institute Davos, Switzerland: Sibylle Grad, Mauro Alini, Amra Šećerović - Institute for Biomechanics, ETH Zürich, Zürich, Switzerland: Stephen J Ferguson - SNSF / Sinergia - The SBR project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 874896.
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ORTHOMANUFACTURE, April 26 to 27, 2023, Beaulieu congress center Lausanne, Switzerland