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Fracture hematoma proteomics: surgical invasiveness characterizes the early fracture healing cascade after multiple trauma

ABSTRACT: Purpose The aim of this study was to determine the fracture hematoma (fxH) proteome after multiple trauma using label free proteomics, comparing two different established surgical treatment strategies. Basic procedures A large animal (sus scrofa), multiple trauma animal model was used in which two different trauma surgical treatment methods were compared: Early Total Care (ETC) versus Damage Control Orthopedics (DCO). fxH was harvested after 72 hours and analyzed using liquid chromatography-tandem mass spectrometry. Protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Main findings The proteome of the early fxH was characterized by immunomodulatory and osteogenic proteins, as well as proteins involved in the coagulation cascade. Distinct, 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 remodeling. On the other hand, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodeling, as well as proteins related to anti-inflammatory and osteogenic processes. Principal conclusions 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 severe multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regenerative capabilities, and gained insights into regulatory mechanisms of fracture healing after severe trauma.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Sus Scrofa Domesticus (domestic Pig)

TISSUE(S): Blood

SUBMITTER: Christel Kuik

LAB HEAD: Martijn van Griensven

PROVIDER: PXD049002 | Pride | 2024-05-24

REPOSITORIES: Pride

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Fracture haematoma proteomics.

Groven Rald V M RVM Kuik Christel C Greven Johannes J Mert Ümit Ü Bouwman Freek G FG Poeze Martijn M Blokhuis Taco J TJ Huber-Lang Markus M Hildebrand Frank F Cillero-Pastor Berta B van Griensven Martijn M

Bone & joint research 20240503 5

<h4>Aims</h4>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.<h4>Methods</h4>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 ide ...[more]

PMID: 38699779

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