The healing of a wound is perhaps the most common, normal regenerative process occurring in living organisms. In warm-blooded animals, the healing process is complex and highly orchestrated. A fundamental requirement for the healing regenerative process is the rapid and effective re-establishment of microcirculation through angiogenesis. Initially, a wound site develops more vasculature (hypervascularization) than the normal tissue that is undergoing repair. The pool of differentiated endothelial cells that participates in wound angiogenesis derives from the local proliferation of endothelial cells of the ruptured microvasculature and from the recruitment of adjacent and circulating hematopoietic stem cells functionally designated as endothelial precursor cells (EPC) or angioblasts. At the wound site the conditions of low oxygen (acute hypoxia) and nutrients triggers the synthesis of key soluble angiogenic vascular growth factors and their receptor. The balanced combination of proliferating endothelial cell and stimulating growth factors ensues the revascularization necessary for tissue regeneration. The healing process is highly efficient. In small injuries, repair occurs mostly unnoticed and without requiring therapeutic intervention. Large injuries with considerable lose of tissue mass such as burns or mechanical force trauma, need intervention and medical/surgical therapies often cannot repair the lost tissues. Very frequently tissues experience gradual and persistent pathological and degenerative changes leading to chronic hypoxia and tissue damage that results in chronic non-healing wounds or ulcers. Given the crucial role of angiogenesis for normal wound healing progression, we have attempted to characterize the key events that regulate wound angiogenesis. To this end, we have used various methods for quantitative assessment of angiogenesis progression in experimental wounds. Our studies include traditional molecular and cellular studies as well as well as more novel quantitative morphometric measurements of the wound vasculature. In particular, we have developed a new method for quantitative analysis of
the angiogenesis response using computer-assisted morphometry based of several algorithms MATLAB?. The method allows for the measurement of vessel length, diameter, tortuousity, and branching complexity. We have also utilized micro Computerized Tomography (uCT) by developing radio-opaque silicon molds of the wound vasculature in experimental models. Using uCT we are able to generate, for the first time, 3D images of the wound vascular bed at various stages of healing. Together, these two methods are powerful, sensitive and yield quantitative morphological information of the wound vasculature. Results from these studies will be presented and compared with other, more traditional methods to study angiogenesis.
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