Wound Healing Schwartz 73s3

Wound Healing

PHASES OF WOUND HEALING • Normal wound healing follows a predictable pattern that can be divided into overlapping phases defined by characteristic cellular populations and biochemical activities: (a) hemostasis and inflammation, (b) proliferation, and (c) maturation and remodeling.

• All wounds need to progress through this series of cellular and biochemical events that characterizes the phases of healing in order to successfully re-establish tissue integrity

• Hemostasis precedes and initiates inflammation with the ensuing release of chemotactic factors from the wound site. • Wounding by definition disrupts tissue integrity, leading to division of blood vessels and direct exposure of extracellular matrix to platelets. • Exposure of subendothelial collagen to platelets results in platelet aggregation, degranulation, and activation of the coagulation cascade.

• Platelet α granules release a number of woundactive substances, such as platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), platelet activating factor (PAF), fibronectin, and serotonin. • In addition to achieving hemostasis, the fibrin clot serves as scaffolding for the migration into the wound of inflammatory cells such as polymorphonuclear leukocytes (PMNs, neutrophils) and monocytes.

• PMNs are the first infiltrating cells to enter the wound site, peaking at 24 to 48 hours. • Increased vascular permeability, local prostaglandin release, and the presence of chemotactic substances such as complement factors, – – – –

interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), TGF-β, platelet factor 4, or bacterial products all stimulate neutrophil migration.

• PMNs are also a major source of cytokines early during inflammation, especially TNF-α3 which may have a significant influence on subsequent angiogenesis and collagen synthesis. • Also release proteases such as collagenases, which participate in matrix and ground substance degradation in the early phase of wound healing.

• The second population of inflammatory cells that invades the wound consists of macrophages, which are recognized as being essential to successful healing. • 5 Derived from circulating monocytes, macrophages achieve significant numbers in the wound by 48 to 96 hours postinjury and remain present until wound healing is complete.

• Macrophages, like neutrophils, participate in wound debridement via phagocytosis and contribute to microbial stasis via oxygen radical and nitric oxide synthesis. • The macrophage’s most pivotal function is activation and recruitment of other cells via mediators such as cytokines and growth factors, as well as directly by cell-cell interaction and intercellular adhesion molecules (ICAM).

• T lymphocytes comprise another population of inflammatory/immune cells that routinely invades the wound. • T-lymphocyte numbers peak at about 1 week postinjury and truly bridge the transition from the inflammatory to the proliferative phase of healing.

• Lymphocytes also exert a downregulating effect on fibroblast collagen synthesis by cellassociated interferon (IFN)-γ, TNF-α, and IL-1. • This effect is lost if the cells are physically separated, suggesting that extracellular matrix synthesis is regulated not only via soluble factors but also by direct cell-cell between lymphocytes and fibroblasts.

Proliferation • The proliferative phase is the second phase of wound healing and roughly spans days 4 through 12. • It is during this phase that tissue continuity is reestablished. Fibroblasts and endothelial cells are the last cell populations to infiltrate the healing wound, and the strongest chemotactic factor for fibroblasts is PDGF. • Upon entering the wound environment,recruited fibroblasts first need to proliferate, and then become activated, to carry out their primary function of matrix synthesis remodeling. This activation is mediated mainly by the cytokines and growth factors released from wound macrophages.

• Fibroblasts isolated from wounds synthesize more collagen than nonwound fibroblasts, they proliferate less, and they actively carry out matrix contraction • Endothelial cells also proliferate extensively during this phase of healing. These cells participate in the formation of new capillaries (angiogenesis), a process essential to successful wound healing. Endothelial cells migrate from intact venules close to the wound. Their migration, replication, and new capillary tubule formation is under the influence of such cytokines and growth factors as TNF-α, TGF-β, and VEGF.

Matrix Synthesis • Biochemistry of Collagen • Collagen, the most abundant protein in the body, plays a critical role in the successful completion of adult wound healing. Its deposition, maturation, and subsequent remodeling are essential to the functional integrity of the wound. Although there are at least 18 types of collagen described, the main ones of interest to wound repair are types I and III. Type I collagen is the major component of extracellular matrix in skin.

• Collagen synthesis, as well as posttranslational modifications, are highly dependent on systemic factors such as an adequate oxygen supply; the presence of sufficient nutrients (amino acids and carbohydrates) and cofactors (vitamins and trace metals); and the local wound environment (vascular supply and lack of infection).

• Proteoglycan Synthesis • Glycosaminoglycans comprise a large portion of the “ground substance” that makes up granulation tissue. Rarely found free, they couple with proteins to form proteoglycans. The polysaccharide chain is made up of repeating disaccharide units composed of glucuronic or iduronic acid and a hexosamine, which is usually sulfated.

• The major glycosaminoglycans present in wounds are dermatan and chondroitin sulfate. Fibroblasts synthesize these compounds, increasing their concentration greatly during the first 3 weeks of healing. • As scar collagen is deposited, the proteoglycans are incorporated into the collagen scaffolding. However, with scar maturation and collagen remodeling, the content of proteoglycans gradually diminishes

TREATMENT OF WOUNDS

Local Care • Management of acute wounds begins with obtaining a careful history of the events surrounding the injury. The history is followed by a meticulous examination of the wound. • Examination should assess the depth and configuration of the wound, the extent of nonviable tissue, and the presence of foreign bodies and other contaminants.

• Examination of the wound may require irrigation and débridement of the edges of the wound and is facilitated by use of local anesthesia. • Antibiotic istration and tetanus prophylaxis may be needed, and planning the type and timing of wound repair should take place

Management of acute wound 1. a. b. c.

Examination depth? Underlying structures injury Configuration? Nonviable tissue?

2. Preparation a. Anasthetic b. Exploration c. Cleansing d. Hemostatis e. Debride nonviable tissue f. Betadine g. Antibiotics h. tetanus

3. Approximation a. Deep layers a. Fascial layers only b. Absorbable suture b. Superficial layers a. Meticulous alignment b. Nonabsorbable sutures in skin c. Monofilament d. Dermal glues

4. follow-up a. cellulitis/drainage? b. Suture removal a. 4-5 days for face b. 7-10 days other skin

Antibiotics • Antibiotics should be used only when there is an obvious wound infection. Most wounds are contaminated or colonized with bacteria. • The presence of a host response constitutes an infection and justifies the use of antibiotics. Signs of infection to look for include erythema, cellulitis, swelling, and purulent discharge. • Indiscriminate use of antibiotics should be avoided to prevent emergence of multidrugresistant bacteria.

Dressing • The main purpose of wound dressings is to provide the ideal environment for wound healing. The dressing should facilitate the major changes taking place during healing to produce an optimally healed wound. Although the ideal dressing still is not a clinical reality, technological advances are promising. • Dressings can be classified as primary or secondary. A primary dressing is placed directly on the wound and may provide absorption of fluids and prevent desiccation, infection, and adhesion of a secondary dressing. A secondary dressing is one that is placed on the primary dressing for further protection, absorption, compression, and occlusion. Many types of dressings exist and are designed to achieve certain clinically desired endpoints.

• Absorbent Dressings. Accumulation of wound fluid can lead to maceration and bacterial overgrowth. Ideally, the dressing should absorb without getting soaked through, as this would permit bacteria from the outside to enter the wound. The dressing must be designed to match the exudative properties of the wound and may include cotton, wool, and sponge. • Nonadherent Dressings. Nonadherent dressings are impregnated with paraffin, petroleum jelly, or water-soluble jelly for use as nonadherent coverage. A secondary dressing must be placed on top to seal the edges and prevent desiccation and infection. • Occlusive and Semiocclusive Dressings. Occlusive and semiocclusive dressings provide a good environment for clean, minimally exudative wounds. These film dressings are waterproof and impervious to microbes but permeable to water vapor and oxygen.

• Hydrophilic and Hydrophobic Dressings. These dressings are components of a composite dressing. Hydrophilic dressing aids in absorption, whereas a hydrophobic dressing is waterproof and prevents absorption. • Hydrocolloid and Hydrogel Dressings. Hydrocolloid and hydrogel dressings attempt to combine the benefits of occlusion and absorbency. Hydrocolloids and hydrogels form complex structures with water, and fluid absorption occurs with particle swelling, which aids in atraumatic removal of the dressing. Absorption of exudates by the hydrocolloid dressing leaves a yellowish-brown gelatinous mass after dressing removal that can be washed off. Hydrogel is a cross-linked polymer that has high water content. Hydrogels allow a high rate of evaporation without compromising wound hydration, which makes them useful in burn wound treatment.

• Alginates. Alginates are derived from brown algae and contain long chains of polysaccharides containing mannuronic and glucuronic acid. The ratios of these sugars vary with the species of algae used, as well as the season of harvest. Processed as the calcium form, alginates turn into soluble sodium alginate through ion exchange in the presence of wound exudates. The polymers gel, swell, and absorb a great deal of fluid. Alginates are being used when there is skin loss, in open surgical wounds with medium exudation, and on full-thickness chronic wounds.

• Absorbable Materials. Absorbable materials are mainly used within wounds as hemostats and include collagen, gelatin, oxidized cellulose, and oxidized regenerated cellulose. • Medicated Dressings. Medicated dressings have long been used as a drug-delivery system. Agents delivered in the dressings include benzoyl peroxide, zinc oxide, neomycin, and bacitracinzinc. These agents have been shown to increase epithelialization by 28%.

Skin Replacements • All wounds require coverage in order to prevent evaporative losses and infection and to provide an environment that promotes healing. Both acute and chronic wounds may demand use of skin replacement, and several options are available.

• Conventional Skin Grafts. Skin grafts have long been used to treat both acute and chronic wounds. Split- (partial-) thickness grafts consist of the epidermis plus part of the dermis, whereas fullthickness grafts retain the entire epidermis and dermis. Autologous grafts (autografts) are transplants from one site on the body to another; allogeneic grafts (allografts, homografts are transplants from a living nonidentical donor or cadaver to the host; and xenogeneic grafts (heterografts) are taken from another species (e.g., porcine). Split-thickness grafts require less blood supply to restore skin function. The dermal component of full-thickness grafts lends mechanical strength and resists wound contraction better, resulting in improved cosmesis. Allogeneic and xenogeneic grafts require the availability of tissue, are subject to rejection, and may contain pathogens.

• Skin Substitutes. Originally devised to provide coverage of extensive wounds with limited availability of autografts, skin substitutes also have gained acceptance as natural dressings. Manufactured by tissue engineering, they combine novel materialswith living cells to provide functional skin substitutes, providing a bridge between dressings and skin grafts

• Gene or Cell Therapy. Given the disappointing results from the application of purified growth factors onto wounds, the possible therapeutic potential of gene therapy has been recognized and studied. Direct access to the open wound bed, which characterizes almost all chronic wounds, has facilitated this therapy. Gene delivery to wounds includes traditional approaches such as viral vectors and plasmid delivery or, more recently, electroporation and microseeding.

CLASSIFICATION OF WOUNDS • Wounds are classified as either acute or chronic. Acute wounds heal in a predictable manner and time frame. • An incised wound that is clean and closed by sutures is said to heal by primary intention. Often, because of bacterial contamination or tissue loss, a wound will be left open to heal by granulation tissue formation and contraction; this constitutes healing by secondary intention

• Delayed primary closure, or healing by tertiary intention, represents a combination of the first two, consisting of the placement of sutures, allowing the wound to stay open for a few days, and the subsequent closure of the sutures

Factors Affecting Wound Healing