Is Human Fracture Hematoma Inherently Angiogenic?

Street, John; Winter, Desmond C.; Wang, Jiang; Wakai, Abel; McGuinness, A.; Redmond, H. P.

doi:10.1097/00003086-200009000-00033

Cited by 184 publications

(121 citation statements)

References 16 publications

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“…Given that significant cell death occurs in the first 24 h after fracture (21) and that shorter treatments with VEGF protein in vivo were less effective (data not shown), a slow-release formulation (such as that used in the mouse studies) may be necessary to promote optimal healing by VEGF. Such a VEGF formulation could also prove useful in additional indications such as spinal fusion, non-unions, and maxillo-facial surgeries.…”

Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover

Street

Bao

Deguzman

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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1,245

954

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Several growth factors are expressed in distinct temporal and spatial patterns during fracture repair. Of these, vascular endothelial growth factor, VEGF, is of particular interest because of its ability to induce neovascularization (angiogenesis). To determine whether VEGF is required for bone repair, we inhibited VEGF activity during secondary bone healing via a cartilage intermediate (endochondral ossification) and during direct bone repair (intramembranous ossification) in a novel mouse model. Treatment of mice with a soluble, neutralizing VEGF receptor decreased angiogenesis, bone formation, and callus mineralization in femoral fractures. Inhibition of VEGF also dramatically inhibited healing of a tibial cortical bone defect, consistent with our discovery of a direct autocrine role for VEGF in osteoblast differentiation. In separate experiments, exogenous VEGF enhanced blood vessel formation, ossification, and new bone (callus) maturation in mouse femur fractures, and promoted bony bridging of a rabbit radius segmental gap defect. Our results at specific time points during the course of healing underscore the role of VEGF in endochondral vs. intramembranous ossification, as well as skeletal development vs. bone repair. The responses to exogenous VEGF observed in two distinct model systems and species indicate that a slow-release formulation of VEGF, applied locally at the site of bone damage, may prove to be an effective therapy to promote human bone repair.

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Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover

Street

Bao

Deguzman

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

1,245

954

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“…Therefore, the mode of action of the different volume solution agents might have influenced the outcome of the fracture healing process. It is known that, especially in the early stages of fracture healing characterised by haematoma and the inflammation stage, a fast regeneration of blood supply is essential for a successful healing process and the induction of the cascade of cellular activities [6,7,27,28,29,31,31]. An interesting fact was that the blood flow in the soft tissue was unaffected by the shock followed by resuscitation.…”

Section: Discussionmentioning

confidence: 99%

Influence of haemorrhagic shock on fracture healing

Bumann

Henke

Gerngroß

et al. 2003

Langenbeck's Archives of Surgery

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In the shock group the restoration of vascularity in the distal region and in the soft tissue in the early healing stages, provoked by the isovolumic resuscitation, led to enhanced fracture healing. In addition, the results indicate that a fast blood supply may generate an improved initial healing process that results in an increased mechanical outcome of bone healing. In general, our findings underline the close interrelation between blood supply and successful fracture healing.

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“…Increased cytokine and growth factor levels can be detected within the regenerating tissue surrounding fracture, as well as in the peripheral blood of these patients [7,16,30]. Various studies have evaluated the circulating levels of VEGF in patients with fractures of long bones and have uniformly demonstrated that peripheral blood VEGF levels in fracture patients are significantly increased as compared to healthy controls [13,16,30]. Weiss et al also evaluated the serum levels of angiogenin (ANG), angiopoietin-2 (Ang-2), bFGF, and PDGF-AB in patients with successful union of long bone fractures, versus patients with non-union.…”

Section: Inflammatory Phasementioning

confidence: 99%

Vascular Endothelial Growth Factor: An Essential Component of Angiogenesis and Fracture Healing

Beamer

Hettrich

Lane

2010

HSS Journal®: The Musculoskeletal Journal of Hospital for Speci

139

114

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Fractures require adequate stability and blood supply to heal. The vascular supply to long bones is compromised in a fracture, and the ability to heal hinges on the ability of new blood vessels to proliferate from surrounding vessels in a process known as angiogenesis. This process is largely driven by the growth factor, vascular endothelial growth factor (VEGF), whose levels are increased locally and systemically during fracture healing. VEGF is involved in many steps throughout the fracture healing cascade, from initially being concentrated in fracture hematoma, to the promotion of bone turnover during the final remodeling phase. This article reviews the current literature surrounding the role of VEGF and other growth factors in reestablishing vascular supply to fractured bone, as well as medications and surgical techniques that may inhibit this process.

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Is Human Fracture Hematoma Inherently Angiogenic?

Cited by 184 publications

References 16 publications

Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover

Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover

Influence of haemorrhagic shock on fracture healing

Vascular Endothelial Growth Factor: An Essential Component of Angiogenesis and Fracture Healing

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