Use of in vitro bone models to screen for altered bone metabolism, osteopathies, and fracture healing: challenges of com
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REVIEW ARTICLE
Use of in vitro bone models to screen for altered bone metabolism, osteopathies, and fracture healing: challenges of complex models Sabrina Ehnert1 · Helen Rinderknecht1 · Romina H. Aspera‑Werz1 · Victor Häussling1 · Andreas K. Nussler1 Received: 6 May 2020 / Accepted: 3 September 2020 © The Author(s) 2020
Abstract Approx. every third hospitalized patient in Europe suffers from musculoskeletal injuries or diseases. Up to 20% of these patients need costly surgical revisions after delayed or impaired fracture healing. Reasons for this are the severity of the trauma, individual factors, e.g, the patients’ age, individual lifestyle, chronic diseases, medication, and, over 70 diseases that negatively affect the bone quality. To investigate the various disease constellations and/or develop new treatment strategies, many in vivo, ex vivo, and in vitro models can be applied. Analyzing these various models more closely, it is obvious that many of them have limits and/or restrictions. Undoubtedly, in vivo models most completely represent the biological situation. Besides possible species-specific differences, ethical concerns may question the use of in vivo models especially for large screening approaches. Challenging whether ex vivo or in vitro bone models can be used as an adequate replacement for such screenings, we here summarize the advantages and challenges of frequently used ex vivo and in vitro bone models to study disturbed bone metabolism and fracture healing. Using own examples, we discuss the common challenge of cell-specific normalization of data obtained from more complex in vitro models as one example of the analytical limits which lower the full potential of these complex model systems. Keywords Ex vivo bone cultures · Osteoblast/osteocyte · Osteoclast · Endothelial cells · Co-culture · 2D/3D
Introduction Bones of the skeleton are more than the supporting framework for the human body Based on recent statistical investigations, approx. every third hospitalized patient in Europe suffers from musculoskeletal injuries or diseases. Their treatment makes up to 15% of all therapeutic costs (Eurostat), of which most costs being caused by surgical revisions after delayed or impaired fracture healing. A large British study with almost 3000 patients showed delayed or impaired fracture healing in 20% of these patients (Hernandez et al. 2012). Besides the type and severity of the trauma, individual factors including the patients’ age and individual lifestyle (e.g., reduced physical activity, * Sabrina Ehnert [email protected]‑tuebingen.des; [email protected] 1
Siegfried Weller Research Institute at the BG Trauma Center Tübingen, Department of Trauma and Reconstructive Surgery, University of Tübingen, Tübingen, Germany
imbalanced diet, alcohol, or cigarette consumption), as well as emerging chronic diseases and their medication strongly affected fracture risk and fracture healing (Hernandez et al. 2012; Ihle et al. 2017; Schlundt et al. 2018; Sheu and Diamond 2016). Indeed, today, over
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