actions of proteases on ECM components play a key role in regulating angiogenesis and many other aspects of normal wound healing, including the migration of cells into the wound. The process of angiogenesis is stimulated by local factors in the wound microenvironment, including low oxygen tension, low pH and high lactate levels [14] . Several growth factors, including bFGF, TGF-? and vascular endothelial growth factor (VEGF), are also potent angiogenic signals for endothelial cells. It is now recognised that oxygen levels in the tissues directly regulate angiogenesis by interacting with oxygen-sensing proteins that regulate the transcription of angiogenic and anti-angiogenic genes. For example, the synthesis of VEGF by capillary endothelial cells is increased by hypoxia through the activation of the recently identified transcription factor hypoxia-inducible factor (HIF), which binds oxygen [15] . When oxygen levels surrounding capillary endothelial cells drop, levels of HIF increase inside the cells. HIF-1 binds to specific DNA sequences and stimulates the transcription of specific genes, such as that encoding VEGF, that promote angiogenesis. The regulation of angiogenesis involves both stimulatory factors, such as VEGF, and anti-angiogenic factors, such as angiostatin, endostatin, thrombospondin and pigment epithelium-derived factor. The cells that form the new capillaries were assumed to arise from pre-existing capillary endothelial cells, but it is clear from animal experiments that angiogenic factors cause endothelial cells adjacent to an ischaemic site to begin to migrate into the matrix and proliferate, forming new buds or sprouts. However, recent data suggest that some of the cells that form