Wound Healing and Principles of Wound Care

Introduction

Wound healing involves a broad range of overlapping cellular and metabolic processes that are orchestrated as a fundamental homeostatic response to injury. An understanding of these concepts is essential to care for wounds in all disciplines of surgery. Plastic surgeons are often consulted by other practitioners to deal with difficult, nonhealing, compromised wounds. Therefore, an understanding of the basic science of wound healing allows one to identify the variables involved in a given wound, and ultimately modulate the process to restore the structure and function of the injured tissue.

Classically, wound healing is divided into three distinct phases: inflammatory, proliferative and remodeling (Table 1.1). Even though each phase is described as a separate event, there is a large degree of temporal overlap and variability in these phases. Factors that influence the timing and length of these events include ischemia, age of the host, nutrition, radiation, smoking, systemic diseases such as diabetes, contamination or infection, desiccation, and the amount of devitalized or necrotic tissue in the wound. This chapter outlines the cellular, vascular and physiologic events underlying wound healing, focusing on the clinically relevant aspects.

Inflammatory Phase

Immediately after injury, bleeding occurs as a result of disruption of the blood vessels. Hemostasis is obtained by initial transient vasoconstriction and subsequent platelet plug and clot formation. Platelet degranulation of alpha and dense granules releases various substances, including platelet-derived growth factor (PDGF) and transforming growth factor-β (TGF-β), which ignite the chemotaxis and proliferation of inflammatory cells that characterize this phase of wound healing. Following the period of vasoconstriction, the migration of cells to the site of injury is aided by vasodilation and increased endothelial permeability (mediated by histamine, prostacyclin and other substances).

The first cells to arrive are the polymorphonuclear leukocytes (PMNs), which increase in numbers over the first 24 hours. These cells aid in the process of clearing the wound of debris and bacteria. Over the next 2-3 days, macrophages replace the PMNs as the predominant cell type. Macrophages have several critical roles in healing wound, including phagocytosis, release of multiple growth factors and cytokines, and recruitment of additional inflammatory cells. The importance of macrophages is exemplified by studies that have shown that wound healing is significantly impaired without their participation. In contrast, blocking or destroying PMNs during the inflammatory phase still results in a normally healing wound in the absence of bacteria. Finally, lymphocytes populate the wound, although their direct role in wound healing requires further investigation.

Table 1.1. The phases of wound healing

Cellular Vascular Time Phase Response Response Course

Inflammatory PMNs, macrophages, Vasconstriction, followed Injury to lymphocytes by vasodilation 7 days Proliferative Fibroblasts, Angiogenesis, 5 days to endothelium collagen deposition 3 weeks Remodeling Fibroblasts Collagen crosslinking and 3 weeks to increasing tensile strength 1 year

Note: these are overlapping processes and the time course varies depending on local and systemic factors.

Proliferative Phase

The clot formed during the inflammatory phase provides the provisional matrix and scaffolding for the proliferation of the dominant cell type during this phase— the fibroblast. In addition, growth factors stimulate angiogenesis and capillary ingrowth by endothelial cells. The capillaries and fibroblasts form a substrate recognized clinically and histologically as granulation tissue. Fibroblasts produce collagen, which is the principal structural molecule in the final scar. Initially, type III collagen is produced in relative abundance in the healing wound; the normal adult 4:1 ratio of type I to type III collagen is gradually restored during the remodeling phase. The formation of collagen is a multi-step, dynamic process with both intracellular and extracellular components. Procollagen is synthesized and arranges as a triple-helix. After the secretion of procollagen from the intracellular space, peptidases trim residues from the terminal ends, allowing the collagen molecule to associate with other secreted fibrils. Ultimately, hydroxylation and cross-linking of collagen is required for the strength and stability of this protein.

Remodeling Phase

Approximately 2-3 weeks after the initial injury, collagen accumulation reaches a steady-state, where there is no change in total collagen content. During this time, there is replacement of the random collagen fibrils with organized, cross-linked fibrils. This process of remodeling persists for up to a year. Scars continue to gain strength over this phase; however, the tensile strength of scars never reaches that found in unwounded skin, approaching approximately 70% of normal strength.

Epithelialization

The skin is composed of the epidermis and dermis. Among the many important functions of the epidermis is to provide a barrier against bacteria and other pathogens and to maintain an aqueous body environment. When the skin is wounded, epithelialization begins to reconstitute the surface of the wound soon after the initial injury. In partial-thickness wounds, the epithelium derives from dermal appendages, hair follicles and sweat glands. In contrast, in full-thickness wounds, the epithelium migrates from the edges of the wound at a rate of 1 to 2 millimeters per day. A delay of epithelialization leads to a prolonged inflammatory phase, compromising the body’s ability to restore the structure and function of the skin.

Wound Contraction

Myofibroblasts are fibroblasts that contain actin microfilaments, and allow wound contraction to occur. Under certain circumstances, wound contraction is advantageous, because it creates a smaller wound area. However, wound contraction that occurs across a joint, such as the elbow, knee or neck, may create functional limitations.

Pearls and Pitfalls

Understanding the basic science of wound healing has important clinical implications. Hemostasis, adequate debridement of dirty or contaminated wounds, and gentle handling of tissues reduces the inflammatory phase of wound healing. Allowing patients to cleanse their wounds with nonirritating solutions such as water further decreases inflammation. In addition, minimizing tension and dead space during wound closure increases the chance for creating an acceptable scar. Moist wound healing is superior to the healing in a desiccated wound; therefore, dressings should be tailored to create a moist local environment. Finally, an often overlooked facet of wound healing is to optimize nutrition. Patients with chronic or poorly healing wounds often require supplementation to provide the substrates necessary for collagen formation and epithelialization.

Suggested Reading

1. Fine NA, Mustoe TA. Wound healing. In: Greenfield LJ et al, eds. Surgery: Scientific Principles and Practice. 3rd ed. 2001:69.
2. Winter GD, Scales JT. Effect of air drying and dressings on the surface of a wound. Nature 1963; 197:91.
3. Mustoe TA, Pierce GF, Thomason A et al. Accelerated healing of incisional wounds in rats induced by transforming growth factor-β. Science 1987; 237:1333.
4. Burns JL, Mancoll JS, Philips LG. Impairments to wound healing. Clin Plast Surg 2003; 30(1):47-56.
5. Leibovich SJ, Ross R. The role of the macrophage in wound repair: A study with hydrocortisone and antimacrophage serum. Am J Pathology 1975; 78:71.