Table 1. Role and consequence of dysregulation of key matrix proteins during tissue repair.

Matrix protein	Role during tissue repair	Consequences of dysregulation
Collagen type I	protects healing wound forms scar matrix mechano-signalling	deficiency results in impaired wound healing, defective fibroblast proliferation, slow wound closure accumulated in fibrosis
Collagen type III	regulates early stages of repair and fibroblast phenotype	deletion leads to increased myofbroblast differentiation, accelerated wound closure, and increased scar formation
Collagen type IV	basement membrane integrity, regulates neo-vascularization and growth factor release	deletion results in a weaker basement membrane
Collagen type VI	regulates fibroblast apoptosis affects cell spreading and migration involved in collagen fibril organisation	deletion leads to weak basement membrane, altered collagen fibril architecture, less total collagen, and a thinner matrix deficiency affects organization of fibronectin
Collagen type VII	supports fibroblast migration connects basement membrane to interstitial matrix involved in laminin organization	deletion leads to absence of anchoring fibrils and therefore constant wound burden, and perturbed laminin organisation
Collagen type XIV	connects basement membrane to interstitial matrix regulates fibrillogenesis	deficiency results in altered matrix biomechanics (tissue-dependent)
Plasma fibronectin	stabilises fibrin clot substrate for platelet adhesion, spreading and aggregation essential for post-traumatic opsonization	cellular fibronectin can compensate deleted plasma fibronectin where applicable
Cellular fibronectin	enables wound gap closure via fibroblast polarisation and migration required for collagen network formation growth factor activation and mechanosignalling	splicing errors lead to abnormal wound healing accumulated in fibrosis
Laminin	critical for basement membrane assembly, re-epithelialization and angiogenesis involved in regulation of MMPs	deletion results in the lack of a basement membrane
Tenascin	interacts with fibronectin critical for cell-matrix crosstalk	depletion leads to reduced collagen and fibronectin deposition and impaired wound closure due to alterations in fibroblast focal adhesions
Vitronectin	regulates plasminogen activation initiates platelet aggregation regulates growth factor activity	depletion results in delayed coagulation
Glycosaminoglycans	growth factor reservoir regulate fibroblast phenotypes involved in angiogenesis modulate matrix biomechanics and hydophobicity	deletion of syndecan leads to delayed wound healing and impaired angiogenesis loss of heparan sulfate results in impaired wound healing
SPARC	modulates matrix organisation activates TGFβ	deficiency leads to delayed granulation tissue formation and diminished matrix production
CCN proteins	promote matrix protein expression interact with TGFβ signalling involved in neutrophil clearance promote fibroblast adhesion modulate myofibroblast senescence	CCN2 and CCN4 overexpressed in fibrosis
Thrombospondin	facilitates matrix organisation and re-epithelialisation regulate latent TGFβ critical for collagen fibrillogenesis critical for platelet aggregation regulates angiogenesis	depletion results in prolonged inflammatory response and delayed wound healing
Osteopontin	regulates fibroblast phenotype important for collagen organisation	deletion leads to altered collagen fibrillogenesis and matrix organisation
Fibulin	regulates TGFβ and fibroblast migration important for long-term tissue repair	accumulation associated with abnormal tissue repair