Thrombospondins (TSPs) 1 and 2 are extracellular modular glycoproteins that are best known for their anti-angiogenic properties and their ability to modulate cell-matrix interactions. However, these proteins, and in particular TSP2, are pleiotropic in function and affect processes as disparate as bone growth and hemostasis. In recognition of their ability to influence a wide variety of cell functions, and in the absence of convincing evidence for their participation as integral components of extracellular structures, the term 'matricellular' has been applied to these and a small group of functionally related proteins. In this review, we focus on the role of TSP1 and 2 in two forms of injury in mice, excisional skin wounds and subcutaneously implanted biomaterials, and take advantage of mice with targeted disruptions of one or both genes to identify likely biochemical mechanisms that could account for the characteristics of the injury response in these knockout mice. In work that stems largely from our own laboratory, we show that pericellular levels of the matrix metalloproteinase, MMP2, are controlled to a large extent by TSP2 (and potentially also by TSP1), and that elevated levels of MMP2 are likely to account in part for defects as diverse as reduced cellular adhesion, abnormal collagen fibril structure, and increased endothelial cell and vascular proliferation.