Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Matrix metalloproteinases (MMPs), also called matrixins, function in the extracellular environment of cells and degrade both matrix and non-matrix proteins. They play central roles in morphogenesis, wound healing, tissue repair and remodelling in response to injury, e.g. after myocardial infarction, and in progression of diseases such as atheroma, arthritis, cancer and chronic tissue ulcers. They are multi-domain proteins and their activities are regulated by tissue inhibitors of metalloproteinases (TIMPs). This review introduces the members of the MMP family and discusses their domain structure and function, proenyme activation, the mechanism of inhibition by TIMPs and their significance in physiology and pathology.

Wound healing is a complex process that can be divided into at least 3 continuous and overlapping processes: an inflammatory reaction, a proliferative process leading to tissue restoration, and, eventually, tissue remodeling. Wound healing processes are strictly regulated by multiple growth factors and cytokines released at the wound site. Although the desirable final result of coordinated healing would be the formation of tissue with a similar structure and comparable functions as with intact skin, regeneration is uncommon (with notable exceptions such as early fetal healing); healing however results in a structurally and functionally satisfactory but not identical outcome. Alterations that disrupt controlled healing processes would extend tissue damage and repair. The pathobiologic states may lead to chronic or nonhealing wounds or excessive fibrosis.