Keywords: mass spectrometry imaging, skeletal trauma, bone healing, methodological developments

"Clinical application of mass spectrometry imaging for analysis of bone and cartilage. Towards improved molecular understanding of impaired skeletal healing."

Different developments necessary for the application of different mass spectrometry imaging techniques on skeletal tissue are presented in this thesis. Sample preparation protocols for undecalcified bone and fracture hematoma were optimized for analysis with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Time-dependent changes in the lipid profiles were observed during fracture healing in human fracture hematoma. In addition, different lipid profiles were seen between the citrulline supplementation and control group during different fracture healing phases in a rat model. Protein and pathway analyses showed an enhancement of fracture healing in the citrulline supplementation group in comparison to the control group. An automated setup for laser-assisted rapid evaporative ionisation mass spectrometry (LA-REIMS) was developed for the analysis of sample surfaces with height variations. This setup allowed for the visualization of molecular distributions for a wide variety of samples, including human femoral heads. The different methodological developments and the applications shown in this thesis can be used for future research in skeletal tissue and its healing processes to improve molecular understanding and outcome prediction.

Language: Dutch and English

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