Wound healing occurs in three stages and is characterized by changes in cellularity as different cell types migrate into and out of the wound bed.
Recent advances in the bioregulation of normal wound repair include means for decreasing adhesion formation, the use of growth factors as a strategy for increasing early repair strength, and tissue engineering for the creation of replacement tissues.
Wounds are evaluated in terms of risk factors for altered healing, the presence or absence of infection, physical location, size, appearance, and the stage of healing.
The key issue in wound management is understanding the physiologic effect of such treatment steps as debridement, cleansing, disinfection, dressing, or the use of modalities of motion on the natural response of wound healing.
Comprehensive treatment of the patient with an upper extremity injury is often initiated within days following injury or surgery. Knowledge of the biology of the wound-healing process is an integral component of successful hand therapy practice. The purpose of this chapter is to review both seminal literature that has stood the test of time and offer current evidence as a means of advancing therapeutic intervention in the treatment of the healing wound.
Stages of Wound Healing
Knowledge of wound biology and the physiology of tissue repair is the basis of clinical decision making in the treatment of the simple, complex, or multilayered wound.
Wound healing is a cellular event. Each phase of wound healing is characterized by changes in cellularity as different cell types, primarily neutrophils, monocytes, macrophages, fibroblasts, and endothelial cells, migrate into and out of the wound bed ( Fig. 18-1 ). This cellular activity, initiated by tissue and platelet disruption, is regulated by a complex interaction of biochemical exchanges that orchestrate the events of phagocytosis, neovascularization, and biosynthesis of reparative collagen.
The dramatic changes in wound-healing activity usually are divided into three overlapping stages. In the first stage of repair, the inflammatory or exudative stage, the neutrophil and macrophage are responsible for clearing the wound of debris to set the stage for subsequent repair. The macrophage is the most important regulatory cell in the inflammatory stage because it is critical to bactericidal control and is chemotactic to the fibroblast. Secretory products of the macrophage can enhance fibroblast proliferation and collagen synthesis. The macrophage also may be important in the normal process of angiogenesis—the formation of new blood vessels in granulation tissue. A nonmitogenic chemoattractant for endothelial cells, possibly derived from macrophages, has been isolated from wound fluid.
The migration of epithelial cells, the process known as epithelialization, is initiated within hours of injury, sealing the cleanly incised and sutured wound within 6 to 48 hours. Epithelial cell movement is stimulated by an apparent loss of cellular contact that occurs with wounding and is stimulated by the process of contact guidance. This cellular migration is terminated when advancing cells meet similar advancing cells by the phenomenon known as contact inhibition. Epidermal cells migrate toward the area of cell deficit, following the predictable pattern of mobilization, migration, mitosis, and cellular differentiation. The cells maintain their numbers by mitosis, both in fixed basal cells away from the wound edges, and in migrating cells, with the net result being a resurfacing of the wound and thickening of the new epithelial layer. This reepithelialization process is influenced and possibly directed by a bath of cytokines arising from cells in the wound environment and in distant tissues.
In the second stage of healing, the fibroblastic or reparative stage, the fibroblast begins the process of collagen synthesis. The fibroblast, signaled by the macrophage, growth factors, or other mononuclear cells, initially secretes the elements of ground substance, protein polysaccharides, and various glycoproteins, and at approximately the fourth to fifth day after wounding, collagen synthesis begins.
The myofibroblast, a highly specialized form of fibroblast, is thought to be responsible for the phenomenon of wound contraction. This contractile fibroblast has the characteristics of both the smooth muscle cell and the fibroblast and is found in open granulating wounds, whereas fibroblasts are found in closed incised wounds. Researchers have suggested that the histologic existence of myofibroblasts is related to a transitional state of fibroblasts in granulation tissue, wherein they prepare to migrate from a healed wound.
Endothelial cells form the new blood vessels in granulation tissue, which provide oxygen and nutrients to the wound site. These nutrients are necessary for the synthesis, deposition, and organization of the extracellular matrix. Angiogenesis is thought to be directed chemically by growth factors and macrophage-secreted angiogenic peptides.
The third stage of wound healing is characterized by the maturation and remodeling of scar tissue or extracellular matrix manufactured during the second or reparative stage. This phase is typically observed after the 21st day, terminating months and perhaps years after the wound has occurred. As the healing tissues demonstrate decreased elasticity, a heightened awareness to stress at the wound site reduces the risk of skin breakdown during the reparative stage.
Age is an important factor to consider in the analysis and management of the healing wound. Increased elasticity and strength of connective tissue facilitates both resilience and healing in the young patient. As aging occurs, a decrease in collagen elasticity and fat deposition hinder protective capabilities, resulting in skin that is more easily damaged. Chronic diseases, such as diabetes mellitus and renal failure, can confound the wound-healing process, leading to an increased risk for infection and amputation.
Inasmuch as evidence of the cellular sequence of wound healing is abundant and consistent, histologic research has progressed to analyses of molecular events during the healing process. In the specialty of hand surgery, basic science research in the past two decades has focused on modulation of wound healing and adhesion formation, primarily in the healing flexor tendon.
Advances in Basic Science
Histologic research in wound healing has significantly evolved over the past three decades. Early studies manipulated the microenvironment of the wound and attempted to enhance cellular activity. Experimental modalities were pursued for the control or stimulation of wound healing and included peptides, cytokines, growth factors, and wound fluids. More recent advances in the bioregulation of normal wound repair include means for decreasing adhesion formation, the use of growth factors as a strategy for increasing early repair strength, and tissue engineering for the creation of replacement tissues.
Modulation of Adhesion Formation
Collagen is the most abundant protein in the human body, significantly contributing to the integrity of connective tissue structures. Despite the integral role of collagen synthesis in wound healing, excessive proliferation of collagen can limit excursion and, ultimately, the function of healing tissues in the upper extremity. Collagen synthesis has been associated with fibroblastic activity, and, as such, the chemical modulation of fibroblasts has been experimentally pursued.
Decreased synovial thickening and adhesion formation were observed following intraoperative application of 5-fluorouracil (5FU) in a chicken model. In a subsequent study, adhesion reduction did not result in significant differences in excursion, maximal load, or work of flexion compared with results in normal controls. 5FU has been suggested to have a preferential effect on fibro-osseous fibroblasts, and these cells have been specifically targeted as highly responsible for adhesion formation. Other chemical inhibitors, including those targeting proteinase and prostaglandin, have been noted to decrease adhesions in animal models.
Hyaluronic acid is a glycosaminoglycan found in the extracellular matrix of skin, cartilage, and synovial fluid. Noted to decrease scar formation and promote healing this carbohydrate has also been found in human amniotic fluid. Injection of human amniotic fluid coupled with tendon sheath repair resulted in fewer adhesions and a higher tensile strength in a rabbit model.
Human amniotic fluid also contains growth factors, naturally occurring proteins that stimulate growth. Because research in adhesion modulation has offered limited clinically observable results, the tensile strength as afforded by growth factors has facilitated a transition toward the cellular repair processes that might accelerate tendon healing.
Acceleration of Healing
Vital to the process of wound healing, the differentiation of cell types in the intrasynovial flexor tendon has increased comprehension of both adhesions and tensile strength. Previously differentiated as extrinsic versus intrinsic, the analysis has expanded to consider the catalysts for collagen production at three distinct sites: the tendon sheath, epitenon, and endotenon. The delicate balance of scar tissue necessary for tendon integrity as opposed to adhesion formation has guided the careful analysis of growth factors and cell regulation.
The healing process of the intrasynovial flexor tendon has been studied using both in vitro and in vivo animal models. Using a rat model in vivo, Oshiro and colleagues demarcated the following sequence: superficial repair, initiation of collagen degradation at day 7, near completion of collagen degradation at day 21, synthesis of new collagen with remodeling, and neovascularization. In this study, preexisting endotenon fibroblasts were observed as the primary reparative cells when no gapping occurred. This concurred with seminal work by Gelberman and coworkers, who contrasted the role of epitenon fibroblasts in gapped tendons with endotenon fibroblasts in those tendons in which gapping had not occurred. In their study, Oshiro and colleagues also identified matrix metalloproteinases (MMPs) involved in collagen degradation and remodeling.
An in vitro study of normal rabbit tendons addressed the role of lactate in collagen production. Lactate was noted to stimulate both collagen and growth factors and to affect all cell types. Tendon sheath fibroblasts, however, exhibited the greatest proliferation and collagen production. Tendon sheath cells were also analyzed in a rat model to determine their presence in the healing flexor tendon. These cells were observed at 24 hours, increased in number through the fifth postoperative day, and decreased by day seven.
The influence of vanadate added to drinking water was studied in two rat models. Following medial collateral ligament repair, vanadate yielded a significant increase in collagen fiber diameter, promoted collagen organization, and significantly increased biomechanical stiffness and ultimate force.
Basic fibroblast growth factor (bFGF) has been detected in both normal and injured intrasynovial tendons with increased levels in the epitenon and tendon sheath cells during the first eight weeks of healing. This growth factor has been extensively studied, with implications toward increased proliferation of tenocytes for collagen production. Using a normal rabbit model in vivo, bFGF was observed to increase expression of nuclear factor κB (NF-κB), a cell proliferation regulator. NF-κB has been suggested as a possible signaling pathway among growth factors, cell proliferation, and collagen synthesis, yet clear cause and effect has not been established. The delivery of bFGF to the healing tendon has also been studied. Adeno-associated viral vectors (AAV2) significantly increased expression of bFGF in vitro, and bFGF-coated nylon suture increased strength and epitenon thickening in vivo.
Transforming growth factor beta (TGF-β) has been noted to increase fibroblast recruitment and collagen production, producing significant increases in collagen observed in epitenon, endotenon, and tendon sheath cells in response to all isoforms. These proliferative characteristics spurred the research of TGF-β antibodies, found to decrease adhesions and increase range of motion after repair and generally reduce the profibrotic effects in all three types of cells.
In vitro animal models have established the presence of vascular endothelial growth factor (VEGF) in the healing flexor tendon. This protein has been observed as more prevalent in intrinsic tenocytes than in epitenon cells, peaking between 7 and 10 days after repair and returning to baseline by day 14. An in vivo rat Achilles tendon repair study attributed increased tensile strength to VEGF. Platelet-derived growth factor (PDGF) has been differentially established as present in healing versus normal canine tendons. This protein is commercially available for use in chronic wound management, with improved rate of healing being documented in clinical trials.
As understanding of the influence of growth factors has increased, comparative studies have helped to establish their individual roles. An in vitro rat tendon model comparing VEGF and PDGF identified the former as less favorable. VEGF was noted to significantly increase TGF-β, leading to adhesions, and the collagen produced was three times weaker than that stimulated by PDGF. PDGF and bFGF were also preferable to VEGF and bone morphogenetic protein 2 (BMP-2) in a normal canine model, with increased cell proliferation and collagen production comparatively.
Engineering of Tissues
The concept of tissue engineering has been the focus of much study in the past decade. Woo and associates define tissue engineering as the manipulation of biochemical and cellular mediators to effect protein synthesis and to improve tissue remodeling. The new biologic therapies being developed from this basic science research include the application of growth factors to cutaneous wounds and the use of polymer scaffolds, cells, and growth factors to create replacement tissues.
Growth factors have been marketed primarily via products that interact with biologic tissues, often through impregnation in biologic dressings. These dressings are often referred to as skin substitutes, dermal matrix products, or scaffolds, and function as a vascularized dermis for subsequent split-thickness skin grafting.
Current clinical expectations for these dressings include the following: the dressings must be safe, not cause an immunogenic response, not transmit disease, not be cytotoxic, and not cause excess inflammation. Additional properties of interest include biodegradability, ample stability to support tissue reconstruction, sufficiently long shelf life, availability, and ease in handling. Integrated sheets, carriers, and sprays have been implemented successfully as dermal substitutes.
Integra (Integra LifeSciences, Plainsboro, NJ) is a well-known dermal substitute that has been specifically reviewed following use in the hand. This collagen-based wound repair biomaterial was initially approved as a defect filler for the treatment of severe burns, allowing coverage of large full-thickness wounds to allow delayed split-thickness skin grafting. In a case study offered by Carothers and coworkers, Integra was sutured in a wound bed following tumor excision in the proximal palm. It is of note that both the median nerve and flexor tendons were exposed following tumor removal. The patient was discharged home 1 day postoperatively and encouraged to complete digital motion as a means of decreasing adherence of the exposed structures on the skin substitute. The patient underwent subsequent layering of Integra and split-thickness skin grafting 7 weeks after the initial coverage, resulting in full functional use without tendon adhesions.
Four major challenges have been identified in the study of dermal replacement: safety, substitution for split-thickness skin grafting, improvement of angiogenesis in replacement tissue following graft, and increased ease of use. One identified benefit is that tissue-engineered skin could optimally decrease the use of animals in pharmaceutical testing.
Growth factors have also been studied for direct application to healing bone and ligament. The use of BMP-2 has yielded successful results in human studies of spinal fusion.
The interdisciplinary field of regenerative medicine includes the sciences of biology and engineering. Procedures in this field are enabled by the use of scaffolds, cells, and growth factors. Polymer scaffolds are the structural base on which tissues are grown. The ideal scaffold as described by Chong and associates is a biocompatible mechanism that demonstrates the integrity and ability to house cells until new tissue regenerates. Currently, the size of scaffolds has proved problematic in the maintenance of living cells, and technology for injectable systems is under study. Bioreactors have been employed for cyclic loading, a procedure that mimics stress and establishes desired physical and biochemical properties.
The use of stem cells for tissue engineering has created notable public and scientific controversy. The ethical considerations associated with acquisition of embryonic stem cells and the possibilities of cloning are sources of heated debate. The plasticity of multipotent adult stem cells has been suggested as comparable to embryonic stem cells and is certainly less controversial. Adult mesenchymal stem cells can be harvested from bone marrow and fat, and these cells are capable of all types of differentiation, including osteogenesis, myogenesis, neurogenesis, and angiogenesis. In a rabbit model, epitenon tenocytes, tendon sheath cells, bone marrow–derived stem cells, and adipoderived stem cells all contributed to the successful engineering of flexor tendons; however, use of stem cells hastened proliferation.
Growth factors are applied to facilitate collagen synthesis and subsequent accrual of strength in the engineered tissues. Despite continued research of growth factors, questions remain regarding necessary concentrations and optimal transfer techniques. A complete understanding of cell differentiation and signaling pathways for such differentiation has not been established.
The successful engineering of a flexor tendon was reported by Cao and colleagues in 2002, and Wang and coworkers have quite recently engineered an extensor tendon complex using human fetal extensor tenocytes in an ex vivo rat model. Bone marrow–derived stem cells implanted via hydrogel scaffold have also contributed to cartilage formation in the subcutaneous tissue of mice.
Continued experimental advances in wound healing and tissue engineering will predictably alter clinical management of repaired tendon, nerve, and the complex wound. The integration of biotechnology and the biochemical aspects of wound research may have tremendous relevance to our specialty because many of these new treatments will serve to regulate cellular activity. The application of a more scientific approach to wound healing may alter scar deposition and speed healing, decreasing the associated factors of morbidity: delayed healing, pain, excess fibrosis, longer treatment time, and increased expense. Treatment that may be helpful but not critical for the uncomplicated wound may be obligatory for the complex wound.
This new technology will most likely alter future treatment techniques, but these new techniques do not have much clinical application for the hand clinician as of this writing. For the most part, management of the upper extremity cutaneous wound by the hand surgeon or hand therapist is not an issue. The cleanly incised and sutured wound epithelializes within 6 to 48 hours, and the noninfected wound allowed to heal by secondary intention is expected to contract at a predictable pace. The normal phases of wound healing usually proceed without difficulty when the wound is managed with careful debridement of nonviable tissue, physiologic repair, and routine wound care with cleansing and dressing. The hand clinician, in most cases, focuses attention on the schedules for healing, immobilization, and mobilization for the deeper injured and repaired tissues. However, with complications of infection or dehiscence, and healing altered by malnutrition, irradiation, medication, immunosuppression, or a poor local blood supply, wound management becomes more of an issue and the significance of scientific clinical management becomes more apparent. Depressed healing associated with vasculitis, venostasis, diabetes, immunosuppression, and burn care has inspired much of the work produced by multidisciplinary specialties that has produced the new clinical treatments with biologic dressings, oxygen therapy, and growth factors. Cancer research has had a significant effect on the body of wound-healing knowledge, providing the early analysis of peptide growth factors.
The next section addresses clinical decision making in wound evaluation and the effects of therapeutic management techniques on the cellular events in the different stages of wound healing.
Traditional wound assessment is well described in the literature. Wounds are evaluated in terms of risk factors for altered healing, the presence or absence of infection, physical location, size, appearance, and the stage of healing. Wound edema, presence of hematoma, vascular perfusion, and the status of the deeper tissues are noted. The rate of healing in relation to the date of injury or surgery and the duration of previous treatment or chronicity of the wound are important factors in treatment planning.
Assessment of infection includes a review of risk factors for the individual case, visual inspection, and tissue cultures. Before surgery or medical management, the surgeon will have established the factors that are predictive of susceptibility to infection or an altered rate of healing. This information determines timing of technique for wound closure or surgical management. Risk factors are determined based on an accurate history, including information concerning the mechanism of injury, the environment in which the injury occurred, the patient’s medical and immunosuppressive state, systemic or local nutritional status, and previous medical treatment with medication or radiation. These risk factors should be known to the hand therapist and the surgeon because the therapist in most cases is monitoring the wound more intensively than the surgeon. Patients at high risk for infection may need to be seen more often than those who will predictably experience benign wound healing.
Visual inspection helps determine whether a wound is healing with a normal inflammatory response or if, in fact, it has become infected. The cardinal signs of inflammation, redness, swelling, pain, and heat, accompany the biochemical and fluid aspects of the early inflammatory stage of wound healing and are not to be confused with infection. The therapist should understand that purulence does not always represent the presence of infection. If the inflammatory response is exaggerated or if the drainage is purulent, then bacterial counts must be obtained to determine the level of wound contamination.
Clinical measurements of wound sepsis are determined by wound culture. The U.S. Institute of Surgical Research defines wound sepsis caused by bacterial overgrowth as bacterial counts exceeding 10 5 organisms per gram of tissue. Traumatic wounds with multiple layers of injury to skin, muscle, and bone are difficult to evaluate because the colony count may vary at each level.
One must understand that wound healing in the clinical situation occurs in the presence of bacteria; it is the quantity of and not the mere presence of bacteria that alters the reparative process. Acceptable levels of endogenous, nonpathogenic microflora, as opposed to frank infection, determine the rate of wound healing and may actually stimulate tissue repair. Favorable microflora in the wound bed may stimulate epidermal cell migration and healing. Wound fluid monocyte and macrophage counts have been found to be markedly elevated and collagen deposition increased in wounds inoculated with 10 2 organisms. Lower bacterial counts or well-controlled infection have been found to enhance chemotactic and bactericidal activity.
However, in the presence of significant infection (greater than 10 5 organisms per gram of tissue), impaired leukocyte function, decreased chemotaxis, impaired cellular migration, epithelialization, and intracellular killing are noted. Superficial infection may damage new epithelium through the release of neutrophil proteases, and bacterial counts greater than 10 5 may retard wound contraction. Infected wounds are affected adversely by the formation of thicker connective tissue and excessive angiogenesis, which is associated with prolific scar formation. Robson and colleagues, in a review of studies on the effect of bacterial count on fibroplasia, found the results to be inconsistent, but noted that collagen and hydroxyproline contents were consistently higher in infected wounds. Thus, infection control is important not only to the rate of healing but also to the management of scarring, which ultimately can interfere with tissue gliding and excursion for tendon, nerve, ligament, joint, and skin.
The wound healing by primary intention is usually simple to evaluate and treat. Attention in these cases is usually directed to protection of the deeper structures, the status of suture or staples, tension at the suture line, quality or quantity of drainage, and viability of the tissue. These wounds are described in terms of periwound edema, inflammation, infection, wound tension, viability, and rate of epithelialization.
If the wound closed by primary intention develops complications and dehisces, it becomes a wound healing by secondary intention. Wounds left to heal by secondary intention, or the chronic or infected wound, pose more complex questions and require more clinical problem-solving and decision-making skills of the health-care practitioner. The following section attempts to simplify decision making and treatment planning for the hand therapist who may be confused by the many issues surrounding the management of the complex wound.
The Three-Color Concept
A universal classification system introduced by Marion Laboratories in the late 1980s continues to be the standard with which open wounds are characterized. Their approach uses a “three-color concept” to describe wound status. Wounds are described as red, yellow, black, or a combination of two or three colors. The clinical application of this classification system is described by Cuzzel in several articles. The following color descriptions for evaluation and treatment are summaries of her articles. Clinical decision making as it relates to therapeutic management by debridement, cleansing, disinfecting, and dressing is reviewed in a brief synopsis as it relates to wound color ( Table 18-1 ).
|Black Wound||Yellow Wound||Red Wound|
|Description||Covered with thick necrotic tissue or eschar||Generating exudate, looks creamy, contains pus, debris, and viscous surface exudate||Uninfected, properly healing with definite borders, may be pink or beefy red, granulated tissue and neovascularization|
|Debridement||Separate wound debris with aggressive scrubs, irrigation, or whirlpool||Not applicable: avoid any tissue trauma or stripping of new cells|
|Topical treatment||Topical antimicrobials with low white blood cell count or cellulitis|
The Red Wound
The red wound is uninfected, healing according to a predictable schedule, and characterized by definite borders, granulation tissue, and apparent revascularization ( Fig. 18-2 ). The fibroblast, myofibroblast, endothelial, and epithelial cells are active in this wound, orchestrating the events of epithelialization, angiogenesis, and collagen synthesis. Skin-donor sites or surgical wounds healing by secondary intention, as in the case of an open Dupuytren’s release, are examples of red wounds often seen in the hand clinic. Superficial wounds and acute partial or second-degree burns are classified as red wounds if they are uniformly pink in appearance.
Tissue oxygenation determines the color of the wound. A chronic red wound has pale pink to beefy red granulation tissue and usually is in the late stages of repair. Red wounds closing by secondary intention fill with granulation tissue from the edge of the wound to the center, closing by contraction and epithelialization, or they may be closed by grafting at the appropriate time.
Cellular activity in the clean red wound must be protected and facilitated by the appropriate therapy. Therapeutic goals are to protect the local wound environment, maintain humidity, protect the wound fluids from desiccation, and protect the newly forming granulation tissue and epithelial cells. These wounds should be cleansed with lactated Ringer’s solution or for home care with a nondetergent, mild pump soap such as Ivory or Dove. The soap should be applied to the periwound area only and rinsed with running water. Antiseptics should not be used on the red wound. Topical treatment may include an antibiotic ointment if the patient is at high risk for developing infection. The newly forming cells should be protected from noxious mechanical forces (tapes, dry dressings, wet-to-dry dressings, whirlpool agitation, and wound scrubbing). Occlusive or semiocclusive dressings, which are described in a later section, may be used to protect the local wound environment and wound humidity.
The Yellow Wound
The yellow wound may range in color from a creamy ivory to a canary yellow. Colonization with Pseudomonas gives the wound a yellow-green appearance and a distinctive odor. The yellow wound is draining, purulent, and characterized by slough that is liquid or semiliquid in texture; it contains pus, yellow fibrous debris, or viscous surface exudate ( Fig. 18-3 ). The exudate may promote bacterial growth. Cellular activity is dominated by the macrophage, which is stimulated by the presence of bacteria and inflammation. The macrophage functions to clear the tissue of debris and to remove pathogenic organisms; thus, it is critical to bactericidal control and phagocytosis.
Epithelialization and wound contraction, activity controlled by the epithelial cells and myofibroblasts, may be occurring at the pink wound margins but, in general, are delayed until infection or excessive inflammation are under control.
The goal of treatment in the case of the yellow wound is to facilitate cellular activity so that it can evolve into a red wound. Continual cleansing, removal of nonviable tissue, and absorption of excess drainage are important to decrease the workload of the macrophage. These wounds may be aggressively washed with soap and water, irrigated with a water pick or syringe, or treated with sterile whirlpools to separate surface debris and necrotic tissue. Topical antiseptics are cytotoxic and depress leukocyte function, thus depleting the body’s natural defense mechanism and are thus to be avoided. If bacterial proliferation requires control, an antibiotic such as Silvadene or Bactroban, and not a topical antiseptic, should be used in the wound. Wet-to-dry dressings should be placed over only the wound because their application to the periwound area may cause skin maceration. Wet-to-dry dressings should be used with care because their removal may disturb new cells that are forming at the edge of the wound in addition to necrotic tissue. Dressings that absorb excess exudate while maintaining a moist environment, such as semipermeable foams, hydrocolloids, or hydrogels, may be used in the noninfected wound.
The Black Wound
The black wound ranges in color from dark brown to gray-black; it is covered with eschar or thick necrotic tissue ( Fig. 18-4 ). Cellular activity represents several stages of wound repair that may be occurring simultaneously. The macrophage is working to clear the area of bacteria and debris and to signal fibroblasts to the area. The fibroblast and endothelial cells are beginning to synthesize collagen and new vessels as the debris is removed. This cellular activity is facilitated by the removal of the eschar surgically, mechanically, or enzymatically, in an effort to decrease the workload of the macrophage and to allow for unimpeded cellular migration. Eschar impedes cellular migration and proliferation by acting as a mechanical block and provides a medium in which bacteria can proliferate.
Debridement is the therapeutic goal for the black wound. Meticulous and timely debridement decreases the risk of infection and hastens healing by facilitating normal cellular response. These wounds may be debrided surgically, mechanically, or with proteolytic enzymes such as Travase or Elase. Before mechanical debridement, the tissue may be softened as it is cleansed with scrubs or whirlpool to loosen dead tissue from the viable wound bed.
Topical antibiotics may soften eschar and decrease bacterial count. These wounds should be dressed to protect the wound environment, soften eschar, and facilitate autolysis. Synthetic dressings may facilitate autolysis by protecting wound fluids that contain the white cells responsible for phagocytosis.
Understanding the normal cellular activity of wound repair and regeneration is critical to accurate wound assessment, which in turn determines successful wound treatment. The key issue in wound management is understanding the physiologic effect of such treatment steps as debridement, cleansing, disinfection, dressing, or the use of modalities or motion on the natural response of wound healing. These treatments all contribute, either positively or negatively, to that cellular response.
The therapist can contribute to the wound-healing process by using management techniques that protect wound fluids, help prevent or control infection, minimize adverse mechanical influences, and control the collagen maturation process. Physical agents may facilitate cellular movement associated with increased blood flow, epithelialization, and macrophage or fibroblast activity and may have a role in the stimulation of growth factors. The deleterious effects of desiccation, mechanical trauma, and some topical treatments have been studied in terms of their inhibition of normal cellular function, and the results should alter some currently popular, but unscientific, wound management techniques.
Protecting Wound Fluids
The positive role of humidity in wound resurfacing, first reported more than four decades ago, has been recognized as one of the most important factors in wound healing by several researchers. The maintenance of a moist wound environment in the noninfected wound facilitates both biochemical and cellular activity. Wound fluids contain certain growth factors that interact with the host tissue, promote cellular activity, and contribute to wound metabolism. The tissue fluids that accumulate in a wound create a favorable environment for angiogenesis and granulation tissue formation on which epithelialization can occur.
An accelerated rate of healing in moist wounds is supported by histologic evaluation of full-thickness wounds in porcine skin. Neutrophils and macrophages decreased in number more rapidly under moist conditions, and the proliferative phase cells (fibroblasts and endothelial cells) increased more rapidly. More rapid progression to the remodeling phase and advanced angiogenesis were noted in moist compared with dry wounds.
In an unprotected wound, evaporation occurs within hours of tissue disruption, allowing wound fluids to escape the wound bed. An open wound exposed to air for 2 to 3 hours becomes necrotic to a depth of 0.2 to 0.3 mm. The desiccated dermis or scab impedes epithelial cell migration and acts as a mechanical barrier, creating a dell or depression in the wound as the epidermal cells are required to migrate from the wound margins deep beneath the dried tissue. This process is minimized in a wound that is occluded and not allowed to dessicate.
Occlusion refers to the ability of a wound dressing to allow the transfer of water vapor and gases from a wound surface to the atmosphere. The concept of sequestering wound fluids in the noninfected open wound for the purpose of enhancing cellular activity or facilitating autolytic debridement with occlusive or semiocclusive dressings has led to the development of many environmental dressings.
These microenvironmental dressings may be categorized as films, foams, hydrocolloids, hydrogels, and calcium alginates. Although there are substantial differences in these dressings, they are similar in that they maintain wound humidity (are impermeable to water but not always water vapor), may permit exchange of gases, reduce pain, reduce mechanical trauma associated with dressing removal, and absorb exudate in some cases. The properties and indications for the dressings are summarized in Table 18-2 ), and several excellent review articles are recommended for more detailed study.
|Semipermeable Film||Semipermeable Foam||Semipermeable Hydrogel||Hydrocolloid|
|Indications||Clean, minimally exudative wound; red wound, sutured wounds, donor graft sites (split-thickness grafts), superficial burns, IV site dressing, superficial ulcers||Yellow wound, moderate to high exudate, skin ulcers, odiferous cancers, venous ulcers when combined with stockings or pressure dressings||Donor sites, superficial operation sites, chronic damage to epithelium, yellow exudating wounds; may apply over topical antimicrobials||Yellow wounds, friction blisters, postoperative dermabrasions, decubitus ulcers, venous stasis ulcers, cutaneous ulcers|
|Characteristics||Semiocclusive, occlusive, nonabsorbent, transparent, thin, adhesive, resistant to shear, low friction, does not control temperature, permeable to O 2 gas and water, impermeable to water and bacteria||Hydrophilic properties on wound side, hydrophobic on other side; limited absorbent capacity; permeable to water vapor and gas; polyurethane foams with a heat- and pressure-modified wound contact surface||Three-dimensional hydrophilic polymers that interact with aqueous solutions, swell and maintain water in their structure; insoluble in water; conform to wound surface; permeable to water vapor and gas, impermeable to water; tape required for fixation||Combine benefits of occlusion and absorbency; absorbs moderate to high exudate; expands into wound as exudate is absorbed to provide wound support; vision occluded; atraumatic removal; outer layer impermeable to gas, water, bacteria|
|Function||Mimics skin performance protects from pathogens, decreases pain, maintains wound humidity, enhances healing by protecting wound fluids; protects from pressure, shear, friction||Maintains wound humidity absorbs excess exudate, maintains warmth, decrease pain, cushions wound while averting “strikethrough”||Maintains wound humidity; facilitates autolytic débridement; absorbs excess exudate; allows evaporation without compromising humidity; removes toxic components from wound; maintains warmth; decreases pain||Absorbs exudate to form a gel that swells; applies firm pressure to the floor of a deep ulcer; autolytic debridement maintains wound humidity; maintains warmth; removes toxic compounds; decreases wound site|
|Precautions||Only for uninfected, red wounds; apply to dry periwound area; frame wound by 2 in; break-in seal allows microbes to enter wound from dressing margins||Visual monitoring occluded; low adherence, must tape||Permeable to bacteria; for moderate exudate; dehydrates easily; nonadhesive||Vision occluded; do not use on hairy surfaces|
* Disclaimer/contraindications: All environmental dressings must be used in accordance with product information, which provides guidelines for indications, application, and contraindications. Some contraindications are wounds ulcerated into the muscle, tendon, bone; third-degree burns edge-to-edge eschar; wounds associated with osteomyelitis and active vasculitis, ischemic ulcers, and infected wounds. These products are all-inclusive and are not necessarily endorsed by the author or publisher but are provided as a source for further study.
Human skin has measurable transcutaneous electrical potential differences that are decreased with wounding. Dehydration of wound tissue may decrease the lateral electrical gradient thought to control epidermal cell migration. Exposed wounds tend to be more inflamed and necrotic than occluded wounds. In later stages, the dermis of exposed wounds is more fibroblastic, fibrotic, and scarred.
Preventing and Controlling Infection
The therapist can contribute to infection control by using the appropriate therapeutic techniques to maintain a clean wound bed free of necrotic tissue or excess drainage, by protecting the wound from its external environment with the proper dressings, and by instructing the patient concerning home wound care.
Cleanly incised and sutured wounds may be washed with a mild soap and running water as early as 24 hours after surgery. The red wound may be rinsed with lactated Ringer’s solution, which is more biologically compatible with the wound environment than saline. Some wound therapists currently believe that the pH of saline is too acidic for wound care. Saline, however, continues to serve as a common choice for wound cleansing as it does not cause harm to normal tissue and adequately cleanses most wounds.
The red wound should not be scrubbed because this mechanical trauma could disrupt newly forming epithelium and vessels. The yellow and black wound may be scrubbed with a mild soap and water. Dove or Ivory soap are recommended for home care, or Pluronic F-68 or Poloxamer 188, nontoxic surfactants, can be used when more vigorous cleansing is needed. A high-porosity sponge (90 ppi) may be used for mechanical scrubs because it is minimally abrasive and thus inflicts less tissue damage. The object of wound cleansing is to separate soil, particle, and debris from the wound but not to create cellular destruction. Hydraulic irrigation with a water pick or whirlpool are indicated only for yellow and black wounds to loosen debris from the wound bed. Pressures between 4 and 15 psi are recommended for wound cleansing.
Cleansing solutions such as Hibiclens, hexachlorophene, and povidone-iodine (Betadine) may be used on intact skin before surgery on the periwound area, but if applied to the wound itself, they are cytotoxic and invite infection by destroying macrophages.
Several authors have studied the adverse effects of povidone-iodine. Aronoff and coworkers has demonstrated that long-term povidone-iodine topical application may result in systemic absorption with resulting negative effects. Wound epithelialization and early tensile strength are affected negatively by 1% povidone-iodine solution. Researchers have reported that this solution must be diluted to 0.001% concentration to be nontoxic to human fibroblasts. At this strength, the solution is still bactericidal to Staphylococcus aureus. However, Rodeheaver has demonstrated that cleansing with povidone-iodine offers no advantage over cleansing with saline solution. He found the same level of viable bacteria in wounds contaminated with S. aureus when treated with either saline or povidone-iodine. Both hexachlorophene and povidone-iodine scrubs have been found to instantaneously lyse white blood cells that are critical to wound defense, and povidone-iodine damages red blood cells, resulting in significant hemolysis. Feedar and Kloth urge that povidone-iodine solution in whirlpools and on gauze dressings be reconsidered, and other authors recommend cessation of this practice altogether.
Although we all have observed wound healing in the presence of these cleansing agents, it may be that the wounds we have treated could have responded more quickly, decreasing time, discomfort, and expense, had we more carefully protected the wound fluids and cellular environment.
Many wound specialists have condemned the practice of decontaminating a wound after cleansing with topical antiseptics. The often-quoted adage that “the only solution that should be placed in a wound is one that can safely be poured in the physician’s eye” is supported by most wound therapists. Rodeheaver and colleagues has demonstrated that all antiseptic agents are cytotoxic, and their only mechanism of action is to destroy cell walls. Almost four decades ago he reviewed commonly used antiseptics and found iodine, chlorhexidine, peroxide, boric acid, alcohols, hexachlorophene, formaldehyde, hypochlorite, acetic acid, silver nitrate, merthiolate, gentian violet, permanganate, and aluminum salts to be cytotoxic.
Hydrogen peroxide (H 2 O 2 ), which has little bactericidal action, is perhaps misused as often as povidone-iodine. Hydrogen peroxide is appropriately used on a crusted wound, or to cleanse periwound skin, but should not be used after crust separation, on new granulation tissue, or on closed wounds.
Researchers have suggested that topical antibiotics are the only antimicrobial agents that are nontoxic and beneficial to wound cellular activity. Mupiricin (Bactroban) is a broad-spectrum antimicrobial recommended for its bactericidal capacity, which is greater than that of other topical antimicrobials. Neosporin ointment has a wide spectrum of bactericidal activity, including against most gram-positive and gram-negative bacteria found in both human and porcine skin. Zinc bacitracin, which is one of the three antibacterial components of Neosporin, was found to increase epidermal healing by 25% compared with controls. Contaminated blister wounds treated with the triple antibiotic in Neosporin (neomycin, polymyxin B, and bacitracin) ointment demonstrated lower bacterial counts and faster healing than with similar wounds treated with only protection or antiseptics. One percent silver sulfadiazine (Silvadene) cream acts on a wide range of gram-negative and gram-positive bacteria as well as fungi. It has been used to prevent infection in burn wounds and to salvage some or all parts of questionable flaps. Silvadene treatment has been reported to reduce bacterial counts in wounds contaminated with less than 10 5 bacteria in 100% of the cases tested. Silvadene also has been found to speed epithelialization in experimental animal studies.
With each dressing change, the wound should be cleansed thoroughly of these ointments, and surface coagulum should be gently removed so that the fresh application of the topical antibiotic can be in contact with the wound bed. By using only antibiotic ointments and avoiding the use of cytotoxic antiseptics, bacterial count is controlled and macrophage function, so critical to wound defense, is protected. These ointments may speed epithelialization by keeping the wound moist, thereby preventing crust formation and desiccation, which serve as mechanical barriers to cell migration .
Necrotic tissue promotes bacterial growth and, by mechanical impedance, interferes with epithelial cell migration. Removal of this necrotic tissue by meticulous debridement may be the most critical aspect of care to prevent infection in the acute wound and in the management of the contaminated or chronic wound.
Debridement can be accomplished mechanically, enzymatically, or biologically through the normal phagocytic activity of white blood cells (autolysis). Mechanical debridement by the surgeon is a critical component of both primary and chronic care. The therapist can remove small areas of black or gray eschar or debris from combination yellow and black wounds with fine forceps and sharp scissors. The necrotic debris should be separated from the wound edges, working toward the center, to facilitate the process of wound contraction. The yellow wound can be gently debrided with a small bone curette, but care must be taken not to fracture new capillaries at the wound edges. Before mechanical debridement, the wound may be cleansed and softened in a clear-water whirlpool. A scab may serve as a biologic dressing and left in place on a superficial wound, but if drainage occurs from beneath the scab, it must be debrided.
Enzymatic debridement with topical fibrinolysin enzymes such as Travase or Elase may be used to hasten separation of eschars, scabs, or fibrinous coagulum. Collagenase debridement products Biozyme C and Santyl may hydrolyze undenatured collagen or facilitate debridement of difficult necrotic tissue. Feedar and Kloth categorize these topical enzymes as selective, that is, working on only necrotic tissue, and their claim is supported by others who have demonstrated that these enzymes spare viable tissue. Although these proteolytic enzymes may depress leukocyte phagocytosis, they do not significantly interfere with wound healing. Hydrocolloid, alginate, or hydrogel dressings can be used to achieve natural autolytic cleansing.
Autolytic, or biologic, debridement is considered the most selective because it relies on the body’s natural defense system. The noted importance of this natural phagocytic activity has led to the concept of sequestering wound fluids to facilitate macrophage debridement and has led to the development of synthetic dressings that enhance autolytic debridement.
Selective debridement by careful mechanical, proteolytic, or autolytic means facilitates positive cellular response and is indicated for the yellow or black wound. Nonselective debridement, or that which indiscriminately removes both viable and nonviable tissue from the wound, may disturb new epithelial cells and granulation tissue and should be used with discretion. Nonselective methods includes wet-to-dry, wet-to-wet, and dry-to-dry dressings, whirlpool therapy, vigorous scrubs, Dakin’s solution, or hydrogen peroxide solutions.
The act of covering a wound is an attempt to reproduce the barrier function of epithelium. The primary dressing, or that which is placed in direct contact with the wound, provides a barrier to the external environment and functions to prevent infection. Nonadherent, nonabsorbent contact layers, such as Adaptic, Xeroform, Aquaphor, or Transite, may help prevent desiccation and adhesion of the secondary dressing to the wound. These nonadherent contact layers are used postsurgically before the wound is sealed or epithelialized or can be used on a clean, red wound. The red wound can be protected from its environment with nonabsorbent film dressings such as Tegaderm, Opsite, or Bioclusive (see Table 18-1 ). These dressings are impermeable to water and provide all the benefits of moist wound healing previously described. Tegaderm has been used successfully to protect the humidity of exposed tendon in the digit. This film allows complete motion, adheres with an airtight seal to the periwound area, and prevents tendon desiccation until the wound is closed by secondary intention or surgical means ( Fig. 18-5 ). These dressings provide a physiologic solution to a difficult problem, but they are not appropriate for infected wounds.