Fracture haematoma proteomics

Bone and Joint Research, vol. 13, pp. 214–225

Abstract

Aims: The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. Methods: A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Results: The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes. Conclusion: The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma.

Authors 11

1. Rald V. M. Groven

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands

   Division of Trauma Surgery, Department of Surgery, Maastricht University Medical Center+, Maastricht, Netherlands

2. Christel Kuik

   Maastricht University

   Affiliation as printed

   Maastricht Multimodal Molecular Imaging (M4i) Institute, Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, Netherlands

3. Johannes Greven Aachen Experimental Orthopaedics and Trauma Surgery Department of Orthopaedics, Trauma and Reconstructive Surgery

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Experimental Orthopaedics and Trauma Surgery, Department of Orthopaedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Aachen, Germany

4. Ümit Mert Aachen Department of Orthopaedics, Trauma and Reconstructive Surgery

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Orthopaedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Aachen, Germany

5. Freek G. Bouwman

   Maastricht University

   Affiliation as printed

   NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands

6. Martijn Poeze

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   Division of Trauma Surgery, Department of Surgery, Maastricht University Medical Center+, Maastricht, Netherlands

7. Taco Johan Blokhuis

   Maastricht University Medical Centre · Maastricht University

   Affiliation as printed

   Division of Trauma Surgery, Department of Surgery, Maastricht University Medical Center+, Maastricht, Netherlands

8. Markus Stefan Huber-Lang

   Universität Ulm · University Hospital Ulm

   Affiliation as printed

   Institute of Clinical and Experimental Trauma Immunology, University Hospital Ulm, Ulm, Germany

9. Frank Hildebrand Aachen Department of Orthopaedics, Trauma and Reconstructive Surgery

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Orthopaedics, Trauma and Reconstructive Surgery, University Hospital RWTH Aachen, Aachen, Germany

10. Berta Cillero‐Pastor

    Maastricht University

    Affiliation as printed

    Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands

    Maastricht Multimodal Molecular Imaging (M4i) Institute, Division of Imaging Mass Spectrometry, Maastricht University, Maastricht, Netherlands

11. Martijn van Griensven

    Maastricht University

    Affiliation as printed

    Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands