Table 1.

Selected examples of dynamic reciprocity between ECM and cells during wound healing

	Cells →	ECM →	Cells →	ECM →	Cells →
Hemostasis
	Platelets	Bind to exposed collagen via vWF	Platelets degranulate, release growth factors and bioactive lipids, and shift to functional fibrinogen receptors 128 (αIIbβ3 integrins)	Bind to fibrinogen	Platelet aggregation
Inflammation
	Neutrophils and monocytes bind to endothelium (selectins), integrins change from low to high affinity state, tight binding to endothelial cells, release of chemokines	Chemokines bind to heparan sulfate proteoglycans on endothelial cells	Bound chemokines stimulate expression of β1 and/or β2 integrins by neutrophils and monocytes 129	Bind to fibronectin, collagen	Facilitates chemotaxis along cytokine gradient
	Monocytes	Bind to fibronectin	Increases phagocytic capacity 34	Increased degradation of ECM components and other debris	Transition from an inflammatory phenotype (M1) to constructive phenotype (M2)
Migration and Proliferation
	Fibroblasts	Bind to fibronectin	Stimulates production of MMPs 53	MMPs degrade certain ECM components	Enhances cell migration
	Endothelial cells	Bind to ECM via integrins	Integrins connected to cytoskeleton exert tension, maintain cell shape	Disruptions in ECM (e.g., degradation, increased density) alter tension and cell shape	Differentiation, proliferation, or migration (in presence of growth factors) 75
	Keratinocytes	MMPs dissolve hemidesmosomes (ECM attachments), cells detach from basement membrane	Cell shape changes, migration initiated, expression of specific integrins, 109, 130 phagocytosis of ECM debris, release of MMPs 130, 131	Deposition of fibronectin, tenascin-C, laminin-5; cells bind via integrins 130	Guide cell migration
Contraction and Maturation
	Fibroblasts	Bind to fibronectin via αvβ5 orαvβ3 integrins 79	Differentiate into myofibroblasts in presence of TGF-β1 (possibly from self-generated ECM) 80	Interact with collagen via β1 integrins to contract and remodel the wound; Collagen and MMP expression modulated by mechanical tension	Myofibroblast and fibroblast levels decline in response to declining levels of growth factors and induction of CXCL2 cytokines132

ECM=extracellular matrix, MMPs=matrix metalloproteases, vWF=von Willebrand factor