Mechanical stimulation of the pro-angiogenic capacity of human fracture haematoma: Involvement of VEGF mechano-regulation

Groothuis, Aline, Duda, Georg N., Wilson, Cameron J., Thompson, Mark S., Hunter, Morgan R., Simon, Paul, Bail, Hermann J., van Scherpenzeel, Karine M., & Kasper, Grit (2010) Mechanical stimulation of the pro-angiogenic capacity of human fracture haematoma: Involvement of VEGF mechano-regulation. Bone, 47(2), pp. 438-444.

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Compromised angiogenesis appears to be a major limitation in various suboptimal bone healing situations. Appropriate mechanical stimuli support blood vessel formation in vivo and improve healing outcomes. However, the mechanisms responsible for this association are unclear. To address this question, the paracrine angiogenic potential of early human fracture haematoma and its responsiveness to mechanical loading, as well as angiogenic growth factors involved, were investigated in vitro.

Human haematomas were collected from healthy patients undergoing surgery within 72. h after bone fracture. The haematomas were embedded in a fibrin matrix, and cultured in a bioreactor resembling the in vivo conditions of the early phase of bone healing (20 compression, 1. Hz) over 3. days. Conditioned medium (CM) from the bioreactor was then analyzed. The matrices were also incubated in fresh medium for a further 24. h to evaluate the persistence of the effects. Growth factor (GF) concentrations were measured in the CM by ELISAs. In vitro tube formation assays were conducted on Matrigel with the HMEC-1 cell line, with or without inhibition of vascular endothelial growth factor receptor 2 (VEGFR2). Cell numbers were quantified using an MTS test.

In vitro endothelial tube formation was enhanced by CM from haematomas, compared to fibrin controls. The angiogenesis regulators, vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1), were released into the haematoma CM, but not angiopoietins 1 or 2 (Ang1, 2), basic fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF). Mechanical stimulation of haematomas, but not fibrin controls, further increased the induction of tube formation by their CM. The mechanically stimulated haematoma matrices retained their elevated pro-angiogenic capacity for 24. h. The pro-angiogenic effect was cancelled by inhibition of VEGFR2 signalling. VEGF concentrations in CM tended to be elevated by mechanical stimulation; this was significant in haematomas from younger, but not from older patients. Other GFs were not mechanically regulated.

In conclusion, the paracrine pro-angiogenic capacity of early human haematomas is enhanced by mechanical stimulation. This effect lasts even after removing the mechanical stimulus and appears to be VEGFR2-dependent.

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ID Code: 67010
Item Type: Journal Article
Refereed: Yes
Additional Information: cited By (since 1996)12
Additional URLs:
Keywords: Angiogenesis, Bone healing, Haematoma, Mechanoregulation, VEGF
DOI: 10.1016/j.bone.2010.05.026
ISSN: 8756-3282
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Biochemistry and Cell Biology not elsewhere classified (060199)
Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > BIOMEDICAL ENGINEERING (090300) > Biomechanical Engineering (090302)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > CLINICAL SCIENCES (110300) > Orthopaedics (110314)
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: Copyright 2010 Elsevier Inc.
Deposited On: 10 Feb 2014 23:35
Last Modified: 27 Sep 2015 23:57

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