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Microvascular invasion during endochondral ossification in experimental fractures in rats.

Journal article
Authors Hans Mark
Anthony Penington
Ulf Nannmark
Wayne Morrison
Aurora Messina
Published in Bone
Volume 35
Issue 2
Pages 535-42
ISSN 8756-3282
Publication year 2004
Published at Institute of Surgical Sciences, Department of Plastic Surgery
Institute of Surgical Sciences, Department of Orthopaedics
Institute of Anatomy and Cell Biology
Pages 535-42
Language en
Keywords Animals, Fractures, Bone, physiopathology, Immunohistochemistry, Male, Microscopy, Electron, Transmission, Osteogenesis, Rats, Rats, Sprague-Dawley, Reproducibility of Results
Subject categories Medical and Health Sciences


In this study morphologic techniques have been used to detail the angiogenic response that accompanies endochondral fracture healing in a clinically relevant, reproducible rat model. In this displaced fracture, the gap fills with cartilage that later is replaced by bone, via endochondral ossification. A transient periosteal circulation, followed by a permanent medullary circulation accompany this progression. From 2 to 6 weeks, vessels grow out from the periosteal tissue and give rise to vascular buds, which abut directly onto the avascular zone corresponding to the fracture defect. From 3 weeks onwards, a second wave of vessels grows out from the marrow to the cartilage-filled fracture defect, terminating as vascular buds and loops lined by endothelial and perivascular cells. The loops and buds stain strongly for laminin but transmission electron microscopy does not demonstrate an identifiable basement membrane, pointing to a region of active extracellular matrix turnover. These vessels are intimately associated with osteoblasts and newly formed woven bone forming finger-like composite structures that protrude into the mineralized cartilage matrix with which they form a clearly demarcated interface. Invading vessels and woven bone successively replace the cartilage matrix to mediate repair. Both the vascular structures and progression of endochondral ossification observed, closely resemble those described in the normal epiphyseal growth plate, indicating that the fundamental processes are similar. However, there is a difference in the spatial orientation of cells such that the healing front in the fracture model is relatively disorganized, compared to the orderly linear array of cells at the epiphyseal growth plate.

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