Integrin - ICAM Monocyte Actin Integrin - matrix Collagen Collagen - I Collagen - I Basement membrane

Observations regarding the repair of wounds (i.e., wound healing) date to physicians in ancient Egypt and battle surgeons in classic Greece. The liver’s ability to regenerate forms the basis of the Greek myth involving Prometheus. The clotting of blood to prevent exsanguination was recognized as the first necessary event in wound healing. At the time of the American Civil War, the development of “laudable pus” in wounds was thought to be necessary, and its emergence was not appreciated as a symptom of infection but considered a positive sign in the healing process. Later studies of wound infection led to the discovery that inflammatory cells are primary actors in the repair process. Although scurvy (see Chapter 8) was described in the 16th century by the British navy, it was not until the 20th century that vitamin C (ascorbic acid) was found to be necessary for the function of prolyl hydroxylase, an enzyme required for proper folding and stabilization of collagen into a triple helix. The study of wound healing now encompasses a complex environment containing many cell types, matrix proteins, growth factors, and cytokines, which regulate and modulate the repair process. Nearly every stage in the repair process is redundantly controlled, and there is no single rate-limiting step, with the possible exception of the ingress of inflammatory cells. Successful healing maintains tissue function and repairs tissue barriers, preventing blood loss and infection, but is usually accomplished through collagen deposition or scarring (fibrosis). Advances in our understanding of growth factors, extracellular matrix and stem cell biology are improving healing, and offer the possibility of regenerating tissues to their normal architecture and of engineering replacement tissues. Successful repair relies upon a crucial balance between the yin of matrix deposition and the yang of matrix degradation. Regenerative processes are favored when the matrix composition and architecture are unaltered. Thus, wounds that do not heal may reflect excess proteinase activity, decreased matrix accumulation, or altered matrix assembly. Conversely, fibrosis and scarring may result from reduced proteinase activity or increased matrix accumulation. Whereas the formation of new collagen during repair is required for increased strength of the healing site, chronic fibrosis is a major component of diseases that involve chronic injury.