Interactions of the Extracellular Matrix and Progenitor Cells in Cutaneous Wound Healing

Significance: Both chronic wounds and excessive scar formation after cutaneous injury create a formidable clinical problem resulting in considerable morbidity and healthcare expenditure. The deposition and remodeling of extracellular matrix (ECM) components are critical processes in cutaneous healing. Understanding the role of the ECM in directing progenitor and reparative cell fate and activities during wound repair is required to improve wound-care strategies. Recent Advances: In addition to providing structural integrity, the ECM is recognized to play critical roles in regulating progenitor and reparative cell behaviors such as migration, differentiation, proliferation, and survival. The ECM dictates these activities through its binding of adhesion receptors as well as its ability to regulate growth factor bioavailability and signaling. More recently, a key role for mechanical control of cell fate through interaction with the ECM has emerged. Critical Issues: Despite significant advances in understanding the pathophysiology of cutaneous wound repair, problematic wounds remain a significant healthcare challenge. Regenerative medical strategies that either target endogenous stem cells or utilize applications of exogenous stem cell populations have emerged as promising approaches to pathologic wounds. However, the identification of smart biomaterials and matrices may allow for further optimization of such therapies. Future Directions: An efficient and appropriate healing response in the skin postinjury is regulated by a fine balance of the quantity and quality of ECM proteins. A more complete understanding of ECM regulation of the cell fate and activities during cutaneous wound repair is vital for the development of novel treatment strategies for improvement of cutaneous healing.