Clinical use of mass spectrometry (imaging) for hard tissue analysis in abnormal fracture healing

Abstract

<jats:title>Abstract</jats:title><jats:p>Common traumas to the skeletal system are bone fractures and injury-related articular cartilage damage. The healing process can be impaired resulting in non-unions in 5–10% of the bone fractures and in post-traumatic osteoarthritis (PTOA) in up to 75% of the cases of cartilage damage. Despite the amount of research performed in the areas of fracture healing and cartilage repair as well as non-unions and PTOA, still, the outcome of a bone fracture or articular cartilage damage cannot be predicted. Here, we discuss known risk factors and key molecules involved in the repair process, together with the main challenges associated with the prediction of outcome of these injuries. Furthermore, we review and discuss the opportunities for mass spectrometry (MS) – an analytical tool capable of detecting a wide variety of molecules in tissues – to contribute to extending molecular understanding of impaired healing and the discovery of predictive biomarkers. Therefore, the current knowledge and challenges concerning MS imaging of bone and cartilage tissue as well as <jats:italic>in vivo</jats:italic> MS are discussed. Finally, we explore the possibilities of <jats:italic>in situ</jats:italic>, real-time MS for the prediction of outcome during surgery of bone fractures and injury-related articular cartilage damage.</jats:p>

Sample preparation of bone tissue for MALDI-MSI for forensic and (pre)clinical applications

“…In the clinical field, the application of MALDI-MSI related to skeletal diseases can have a great potential, as the current molecular understanding of the underlying processes of, for example, bone fracture healing and non-union development is very limited [16][17][18]. The application of MALDI-MSI on undecalcified bone tissue can be of additional value for improved understanding of molecular pathways involved in different bone diseases.…”

Advances and Emerging Medical Applications of Direct Mass Spectrometry Technologies for Tissue Analysis

“…Recent advances in direct MS technologies have further improved chemical analysis of histologically and molecularly heterogeneous bone tissues. Applications have focused on providing new biological insights and treatment strategies for musculoskeletal disorders including osteoporosis and osteoarthritis (81)(82)(83)(84) and bone fracture healing (85). For example, Rocha et al (82) applied MALDI MSI to identify alterations in lipid profiles of human knee synovium from normal and osteoarthritis-affected patients as well as psoriatic and rheumatoid arthritis tissues.…”

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“…Recent advances in direct MS technologies have further improved chemical analysis of histologically and molecularly heterogeneous bone tissues. Applications have focused on providing new biological insights and treatment strategies for musculoskeletal disorders including osteoporosis and osteoarthritis (81)(82)(83)(84) and bone fracture healing (85). For example, Rocha et al (82) applied MALDI MSI to identify alterations in lipid profiles of human knee synovium from normal and osteoarthritis-affected patients as well as psoriatic and rheumatoid arthritis tissues.…”