GENERAL PRINCIPLES OF WOUND HEALING

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Injury triggers an organized and complex cascade of cellular and biochemical events that result in a healed wound. For didactic purposes, the wound healing response can be divided into three distinct but overlapping phases: (1) hemostasis and inflammation, (2) proliferation, and (3) maturation or remodeling.116 Failure or prolongation in one phase may result in delay of healing or nonclosure of the wound. Wound healing failures remain a significant clinical problem with large impact on health care costs. A better grasp of the fundamental physiology of healing results in a clearer understanding of the pathophysiologic processes that impair healing.

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HEMOSTASIS AND INFLAMMATION

The inflammatory phase is an essential phase of healing, characterized by increased vascular permeability, chemotaxis of cells from the circulation into the wound milieu, local release of cytokines and growth factors, and activation of migrating cells.

Hemostasis precedes inflammation. The accompanying obligatory rupture of vessels exposes the subendothelial collagen to platelets and results in aggregation of platelets and activation of the intrinsic part of the coagulation cascade. The contact

PROLIFERATIVE PHASE

Fibroblasts and endothelial cells are the primary cells proliferating during this phase. Fibroblasts migrate into the wound site from the surrounding tissue. Endothelial cells proliferate from intact venules close to the wound and form new capillaries by the process of angiogenesis. The growth factors and cytokines responsible for the proliferation of these two cell types derive mainly from platelets and activated macrophages. Some of them are stored in the fibrin clot, which is invaded by the

MATURATION AND REMODELING PHASE

The main feature of the maturation phase is the deposition of collagen in the wound. From a clinical viewpoint this is the most important phase of healing because the rate, quality, and total amount of matrix deposition determine the strength of the scar. Many healing deficiencies become clinically manifest secondary to poor collagen deposition, although the underlying cause may vary. The poor matrix deposition in diabetes, for instance, is in part due to reduced inflammation. On the other

WOUND CONTRACTION

Wound contraction is the approximation of the wound edges, and wound contracture is the shortening of the scar itself. Healing by primary or secondary intention determines the role of wound contraction in the healing process. Several theories have been proposed for the mechanisms of wound contraction.112 One proposes that a special cell—the myofibroblast—is responsible for contraction, whereas another theory suggests that the locomotion of all fibroblasts leads to a reorganization of the matrix

ANALYSIS OF THE WOUND FLUID

The wound fluid is believed to reflect the wound environment at any time during the healing process. Therefore, wound fluid has been subjected to many investigations for analysis of growth substances, amino acid composition, and functional effects. It is noteworthy that wound fluid reflects the sum of all specific activities at the time of harvest. Nevertheless, very few comprehensive data are available about the composition of the wound fluid, partially because of different approaches to

SUMMARY

Wound healing is a complex process involving different biologic and immunologic systems. Despite improvements in diagnostics and therapy, wound failures remain a clinical problem. The approach to a nonhealed wound is an interdisciplinary challenge that should not be underestimated. Better understanding of the complex wound-healing cascade helps our approach to wound healing and its possible failure. Manipulations of the involved immunologic features offer future therapeutic strategies.

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    Address reprint requests to Adrian Barbul, MD, FACS Sinai Hospital Baltimore Department of Surgery 2401 West Belvedere Avenue Baltimore, MD 21215

    This article was supported by a grant from the Deutsche Forschungsgemeinschaft (Wi 1499/1-1).

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