Overview of treatment of chronic wounds

INTRODUCTION — 

A chronic wound is physiologically impaired and does not heal or demonstrate a significant reduction in wound size within 30 days. The definition may include "hard-to-heal" wounds or complex wounds. Examples of nonhealing wounds include: infected surgical or traumatic wounds, venous leg ulcers, pressure-induced skin and soft tissue injury, diabetic foot ulcers, ischemic ulcers, ulcers secondary to delayed radiation injury, and immunocompromised, medication-induced, and malignancy-associated wounds [1]. Skin breakdown can also be associated with chronic medical conditions and hard-to-heal wounds, including rheumatoid arthritis, sickle cell disease, pyoderma gangrenosum, calciphylaxis, epidermolysis bullosa, toxic epidermal necrolysis, vasculitis, radiation dermatitis, and infectious diseases (eg, Buruli ulcer and hidradenitis suppurativa).

Local care of chronic wounds includes serial debridement and wound dressings selected for the specific conditions of the wound to promote healing. Other issues common to chronic wounds (odor, bleeding, itching, exudate, and pain) must also be addressed. Underlying medical condition(s) must be evaluated and addressed prior to surgical intervention, which is often needed to manage factors contributing to the chronic wound state and for definitive wound closure once wound bed preparation is completed.

The management of chronic wounds is reviewed. Risk factors for nonhealing and the management of wounds for which there is no expectation of healing are reviewed separately. (See "Risk factors for impaired wound healing and wound complications", section on 'Impaired wound healing' and "Overview of the care of adult patients with nonhealable wounds".)

CHRONIC WOUND STATE — 

A chronic wound may also be defined as one that is physiologically impaired due to a disruption of the wound healing cycle as a result of impaired angiogenesis, innervation, or cellular migration, among other reasons [2,3].

The precise timeline for epithelialization of a wound is multifactorial depending on the patient's comorbidities (eg, diabetes, autoimmune disease, peripheral artery disease, increased body mass index), wound etiology, baseline wound measurement and appearance, anatomic location, nutrition, medications, and compliance with treatment [4]. While there is no specific time frame that clearly differentiates an acute from a chronic wound, some suggest that the lack of approximately 15 percent reduction weekly or approximately 50 percent reduction of the surface area of the wound over one month indicates a chronic state for patients with diabetic foot ulcers [5]. In addition, a validated and reliable pressure ulcer scale for healing (PUSH) and the Bates-Jensen Wound Assessment Tool (BWAT) can be used to assess pressure ulcer progress [6,7]. The PUSH tool has also been validated in diabetic foot ulcer healing [7]. The Leg Ulcer Measurement Tool (LUMT) and the PUSH tool can be used in venous leg ulcer healing [8,9].

Characteristics of chronic wounds that prevent an adequate cellular response to wound-healing stimuli include the accumulation of devitalized tissue, decreased angiogenesis, hyperkeratotic tissue, exudate, and biofilm formation (ie, bacterial overgrowth on the surface of the wound) [10,11]. (See "Clinical assessment of chronic wounds".)

While the fluid present in acute wounds is rich in growth factors and exhibits a balanced interplay of matrix metalloproteinases and various cytokines, which collectively promote tissue repair, the impact of chronic wound exudate on healing is often less favorable. This difference stems from alterations in the biochemical composition of the fluid over time [12]. (See "Basic principles of wound healing" and "Principles of acute wound management", section on 'Importance of moisture'.)

Chronic wound exudate is characterized by persistently elevated levels of pro-inflammatory cytokines, which can hinder fibroblast proliferation and function, thereby impeding the healing process [13]. Furthermore, excessive periwound edema and induration contribute to the accumulation of this detrimental exudate and must be effectively managed to minimize its negative impact on the wound environment and promote healing. This management often involves strategies to reduce swelling and improve lymphatic drainage [14].

GENERAL CARE — 

General management of patients with chronic wounds includes local wound care as well as management of any underlying medical conditions contributing to the chronic wound state.

Overall approach — Local care of chronic wounds includes wound bed preparation following the principles of tissue assessment and debridement of nonviable tissue and the use of wound dressings selected to address the specific conditions of the wound to promote wound healing. Necrotic debris or nonviable tissue should be aggressively removed, ideally using sharp surgical (excisional) debridement, if possible. Infection and causes of inflammation should be addressed. Moisture balance should be controlled. Documentation of the wound characteristics and measurements, including the wound edge and periwound, should be done [15]. Proper local care is an important element of preparing the wound bed for wound closure or accepting a skin graft or flap when indicated. (See 'Wound bed preparation' below.)

Chronic wounds from cutaneous ulceration that occur in the setting of systemic disease states such as vasoocclusive, autoimmune, and inflammatory disorders (eg, rheumatoid arthritis, sickle cell disease, pyoderma gangrenosum, scleroderma) are difficult to treat and are often colonized with antibiotic-resistant bacteria [16,17]. Appropriate medical management of the underlying condition must be addressed prior to any planned definitive surgical procedure.

Surgery has inherent risks, and medical optimization is important to decrease the risk of intraoperative and postoperative complications. The risks and benefits of surgery should be assessed to determine if the surgical intervention is the best course of treatment. Chronic wounds associated with malignancy can often be approached surgically if there are no prohibitive comorbidities and doing so aligns with the patient's goals for care. Even with advanced systemic disease, surgical excisional debridement and coverage of the wound are possible.

However, some patients may be too sick or unable to undergo repeated procedures, which are often necessary to achieve wound closure. For debilitated patients with chronic lower extremity ischemia or malignancy-related wounds on the lower extremity, palliative care or even primary amputation may be a more appropriate course of action [18]. (See "Overview of the care of adult patients with nonhealable wounds".)

Treatment of infection/cellulitis — National Institute for Health and Care Excellence (NICE) clinical guidelines recommend that systemic antibiotic therapy should be reserved for only those wounds that appear clinically infected [19,20]. All chronic wounds are expected to be colonized with microbes; however, this does not assume or indicate the presence of an acute infectious process [21-23]. Chronic wounds contain biofilm microscopic bacteria present in the superficial and deep tissues that may be recalcitrant to treatment with antibiotics and antiseptics. Clinical visualization of slough, debris, and exudate on the wound may be mistaken for biofilm by clinicians [24]. There is no published evidence to support systemic antibiotic therapy as "prophylaxis" in chronic wounds without clinical evidence of infection or as a means to improve the healing potential of wounds. A multimodality approach to reducing bacterial biofilm may involve debridement as well as topical antimicrobial or antiseptic solutions [24].

Clinical signs of wound infection that might warrant antibiotic therapy may be local (cellulitis, lymphangitic streaking, purulence, malodor, wet gangrene, osteomyelitis) or systemic (fever, chills, nausea, hypotension, hyperglycemia, leukocytosis, change in mental status) [25-27]. (See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

In patients with clinical infection, antibiotic therapy should be targeted and determined by wound culture and sensitivity to decrease the development of bacterial resistance. Wound cultures should not be taken as a superficial swab in these situations but rather from the base of the wound after irrigation and debridement [28]. (See 'Wound culture/biopsy' below.)

Glycemic control — Most clinicians make glycemic control a priority when treating wounds. However, there is no robust clinical evidence in support of short-term glycemic control as it directly affects wound healing potential. (See "Perioperative management of blood glucose in adults with diabetes mellitus" and "Glycemic control in critically ill adult and pediatric patients".)

For patients with diabetic foot ulcers, HbA1c should be maintained between 7 and 8 percent [29-31]. (See "Glycemic management and vascular complications in type 2 diabetes mellitus", section on 'Glycated hemoglobin'.)

Patients at risk for the development of chronic wounds often have comorbid conditions associated with immunocompromised states (eg, diabetes). They may not have classic systemic signs of infection, such as fever and leukocytosis on initial presentation [32,33]. In these patients, the presence of hyperglycemia may be a more sensitive measure of infection.

Nutrition support — Patients identified through nutrition screening as being malnourished or at risk of malnutrition should be offered comprehensive nutritional support. While robust, definitive evidence from large, randomized controlled trials directly linking supplemental nutrition to improved wound healing outcomes is still evolving, a strong body of evidence supports the critical role of adequate nutrition in facilitating the complex processes of tissue repair and minimizing the risk of wound complications [34].

Optimal nutrition provides the essential building blocks and cofactors required for the various stages of wound healing, including collagen synthesis, angiogenesis, immune function, and cellular proliferation. Deficiencies in macronutrients like protein and micronutrients such as vitamins A, B, C, E, zinc, and arginine can significantly impair these processes, including omega-3 fatty acids [35,36]. These deficiencies lead to delayed healing, increased susceptibility to infection, and potentially poorer outcomes. Enriched supplements with vitamins, minerals, and antioxidants demonstrated increased wound healing than nonenriched protein supplements for diabetic foot and pressure ulcers [37].

Therefore, a thorough nutritional assessment, including evaluation of protein status, micronutrient levels, and overall caloric intake, is crucial in patients with chronic wounds. Based on this assessment, individualized nutritional interventions, which may include dietary counseling, oral nutritional supplements, or, in some cases, enteral or parenteral nutrition, should be implemented [38]. (See "Clinical assessment of chronic wounds", section on 'Nutrition screening' and "Overview of perioperative nutrition support".)

Pharmacologic therapy

Pain management — Pain associated with chronic wounds, and specifically with dressing changes, should not be ignored. The World Health Organization (WHO) analgesic ladder, which was developed for the treatment of cancer-related pain, is applicable to other types of chronic pain [39]. For patients receiving stable doses of a long-acting opioid around the clock, supplemental doses of a short-acting agent should be considered prior to dressing changes if they are painful. Topical or local anesthetics can be used but may have limited effect. A holistic approach to pain management in wound healing considers psychological and social factors alongside biologic ones. Effective pain management requires understanding that pain is a multidimensional experience shaped by life experiences and that chronic pain can significantly impact an individual's overall quality of life. Assessment of wound-related pain should also be multidimensional, using appropriate tools that consider the individual's ability to assess their pain and incorporating quality of life measures for chronic pain [40].

Various interventions for wound-related pain, including pharmacologic and non-pharmacologic approaches, should be employed. Non-pharmacologic interventions may involve physical activity, moisture management, aromatherapy, and topical applications [41]. Patient education is also crucial, covering the causes of pain, methods for pain relief, and the impact of pain on quality of life. Psychological approaches, such as cognitive behavioral therapies, relaxation techniques, and coping strategies, are important for addressing the psychological factors associated with pain [42]. (See "Approach to the management of chronic non-cancer pain in adults" and "Overview of cancer pain syndromes".)

Potential therapies to aid healing

●Flavonoids influence wound healing through their effects on inflammation, angiogenesis, re-epithelialization, and oxidative stress. They act on key cells (macrophages, fibroblasts, endothelial cells) by modulating the release and expression of specific growth factors, angiogenic factors, and cytokines. Flavonoids can also reduce inflammatory markers, alter macrophage polarization, and regulate matrix metalloproteinases and crucial signaling pathways [43]. Studies investigating aspirin and flavonoids as adjunctive therapy for wound healing have suggested potential benefits; however, because of potential bias and methodologic flaws, the validity of the findings is uncertain [44].

●Meta-analyses have suggested that pentoxifylline may improve the healing rate for venous leg ulcers [45].

WOUND BED PREPARATION — 

Wound bed preparation is defined as the process of removing local barriers to wound healing to maximize the potential for successful healing. This is accomplished primarily through debridement. Wound bed preparation facilitates ordered restoration and regeneration of damaged tissue and may enhance the function of specialized wound care products and advanced biologic tissue substitutes [46].

The wound bed preparation strategy involves a comprehensive assessment of the wound's etiology and patient-centered concerns to categorize wounds as healable, requiring maintenance, or nonhealable (palliative). Healable wounds, defined by adequate blood supply and a cause amenable to correction, are managed through moisture balance, active debridement, and control of local infection or abnormal inflammation. In maintenance and nonhealable wounds, the treatment objectives shift towards maximizing patient comfort by relieving pain, controlling odor, preventing infection via bacterial load reduction, providing conservative debridement of slough, and ensuring appropriate moisture management, including the management of exudate [47].

In general, surgical intervention of chronic wounds, which often requires multiple staged surgical procedures, is used to prepare the wound bed first by removing infected or necrotic debris and subsequently handling any underlying factors contributing to wound chronicity (eg, bony deformities, biomechanical instability, ischemia). If these are successful in converting the chronic wound to an acute state, provisional or definitive wound coverage can be performed. Depending on the size of the wound, it may be left to heal secondarily or undergo wound coverage/closure. (See 'Wound coverage/closure' below.)

Types of debridement — Many types of debridement may be used to prepare the wound bed for optimal healing.

●Surgical excisional debridement involves physically removing dead or necrotic tissue with a scalpel or sharp tool. Enzymatic debridement uses topical medications to break down tissue. (See 'Surgical excisional debridement' below.)

●Autolytic debridement uses the body’s natural enzymes to break down necrotic tissue. (See 'Autolytic' below.)

●Mechanical debridement utilizes the act of washing or scrubbing the wound. (See 'Non-surgical mechanical debridement' below.)

•Biosurgical debridement uses sterile maggots to consume the necrotic tissue.

•Alternative methods of debridement may be helpful when a clinician with expertise in surgical excisional debridement is not available, frequent surgical excisional debridement may not be tolerated, or there are barriers to wound care.

Surgical excisional debridement — The majority of chronic wounds require planned serial debridement to sufficiently prepare the wound bed and restore an optimal wound-healing environment [48]. Sharp excisional debridement is the most appropriate choice for removing large areas of necrotic or infected tissue and is always indicated whenever there is evidence of infection. Surgical excisional debridement also handles undermined wound edges and is used to obtain tissue from the base of the wound for wound culture and pathologic evaluation, as needed. Serial debridement appears to be associated with an increased likelihood of healing [49-54].

Wounds may require serial debridement in the operating room. In some cases, particularly wounds that are larger or more complex, it is more appropriate to debride the wounds in the operating room, even if no definitive closure/coverage is planned, due to the degree of nonviable tissue, degree of contamination, or infection. The operating room is a safer environment for the debridement of such wounds, which often require the management of deeper soft tissue and bone-related issues. Clinic-based debridement often does not allow for sufficiently aggressive removal of nonviable tissue and biofilm due to inadequate pain control and the limited ability to achieve hemostasis [22].

For selected patients for whom serial debridement may not be tolerated or who have barriers that limit frequent clinic visits, enzymatic, mechanical, or autolytic debridement is an alternative. These interventions may be helpful in reducing treatment complexity in the interval between serial debridement. (See "Remote wound care".)

Technique — Sharp excisional debridement uses a scalpel or other sharp instruments (eg, scissors or curette) to remove devitalized tissue and other accumulated debris, pathogens (biofilm), contaminants, and foreign (or other) material. Sharp excisional debridement decreases bacterial load, stimulates wound contraction and epithelialization, and drains areas of infection [55]. Debridement must include the base of the wound as well as the wound perimeter.

Prior to debridement, most chronic wounds benefit from irrigation to decrease bacterial load and remove any loose material [56-58]. Low-pressure irrigation (eg, <15 pounds per square inch) using saline or water with a bulb syringe is usually adequate to remove material from the surface of most chronic wounds. Higher-pressure irrigation may be useful during the initial debridement of highly contaminated wounds. Low- versus high-pressure irrigation and the utility of additives are reviewed separately. (See "Principles of acute wound management", section on 'Irrigation'.)

Bleeding from the surface of the wound commonly occurs during debridement. The propensity for a wound to bleed depends upon the type of wound and the stage of wound healing. Bleeding impairs the ability to see what tissue should be debrided, so if bleeding occurs after a dressing is removed, it should be stopped before commencing debridement. Bleeding can occur from the healing surfaces or the deep layers of the skin at the wound edge. Diffuse bleeding from healing surfaces is managed with gentle pressure. Bleeding from the skin from a subdermal vessel can be coagulated using an electrocautery or a silver nitrate stick, depending on the clinical setting. Once the bleeding stops, debridement can continue.

Wound culture/biopsy — If there is suspicion of infection (purulence, heavy drainage, clinical signs of infection in the surrounding tissue), wound/tissue cultures should be obtained during operative debridement to help direct antimicrobial therapy. Cultures should be obtained from the deepest margins of the wound and, if possible, include tissue from the wound base. The bacterial flora may evolve to a more resistant bacterial phenotype over time. Thus, cultures should be obtained serially if clinically indicated.

A random culture will most likely yield a positive result in a chronic wound environment, even though it may not be pathogenic [22]. This may lead to unnecessary antibiotic treatment.

If the etiology of the wound is unknown or the wound displays atypical characteristics, an excisional biopsy of the wound and/or wound perimeter should also be obtained for histology.

Non-surgical mechanical debridement — Mechanical debridement is a method of wound cleansing that involves the physical removal of devitalized tissue and foreign material from the wound bed. Mechanical debridement uses external forces to achieve debridement. Mechanical debridement plays a crucial role in wound bed preparation by removing barriers to healing and promoting a healthy wound environment. However, it's important to note that mechanical debridement techniques can be non-selective and may cause trauma to the wound bed if not performed carefully. Therefore, the choice of debridement method should be based on a thorough assessment of the wound, the patient's condition, and the clinician's expertise. In many cases, mechanical debridement is used in conjunction with other debridement methods to achieve optimal wound healing.

One of the most common forms of mechanical debridement uses standard gauze. The "wet-to-dry" technique involves applying a moistened gauze dressing to the wound bed, allowing it to dry, and then removing it. As the dressing dries, it adheres to the tissue, and its subsequent removal results in the non-selective removal of both devitalized tissue and viable tissue. While the wet-to-dry version is commonly used, it can be painful and has been largely replaced with "wet-to-moist" (damp) dressings to reduce pain and the inadvertent removal of viable tissue [59].

Other methods of mechanical debridement include the use of curettes, scissors, or forceps to remove necrotic tissue manually. This type of debridement, often referred to as sharp debridement when performed by a trained professional, allows for more targeted removal of devitalized tissue [60]. However, it requires skill and precision to avoid damaging viable tissue, which can be associated with pain and bleeding.

Local wound irrigation is another form of mechanical debridement. This technique uses pressurized fluid to remove loosely adherent debris and bacteria from the wound surface [61]. The effectiveness of wound irrigation depends on factors such as the irrigation pressure, the volume of the irrigant, and the type of solution used. Proper technique is essential to avoid further tissue damage or bacterial contamination.

Proper cleansing of the wound and periwound reduces bacterial bioburden. Simple cleansing includes using cotton pads or gauze [62,63]. A handheld device using fluorescent imaging can localize contaminated areas with live bacteria (>10⁴ colony-forming units/gram) [64,65]. Common bacteria noted with fluorescent imaging are Staphylococcus aureus and Pseudomonas on all skin types [66,67].

Enzymatic — Enzymatic debridement involves applying exogenous enzymatic agents to the wound. Most commonly, collagenase from Clostridium histolyticum is used to remove necrotic tissue from the wound bed (table 1) [68]. Collagenase may promote endothelial cell and keratinocyte migration, thereby stimulating angiogenesis and epithelialization as its mechanism of action rather than functioning as a strict debridement agent [69,70]. Systematic review and meta-analysis support the use of collagenase in pressure ulcers, diabetic foot ulcers, and in conjunction with topical antibiotics for burns [71]. However, the included studies have methodologic flaws and a high risk of bias. Bromelain-based enzymatic debridement has demonstrated eschar removal with faster debridement and healing times, reduced operations, length of stay, cases of sepsis, blood transfusions, and prevention of compartment syndrome [72]. Enzymatic debridement also remains a good option in patients who require debridement but are not surgical candidates.

Biologic — Another method of wound debridement uses the larvae of the Australian sheep blowfly (Lucilia [Phaenicia] cuprina) or green bottle fly (Lucilia [Phaenicia] sericata, medical maggots) [48]. Biologic debridement or "maggot therapy" can be used as a bridge between debridement procedures or for debridement of chronic wounds when surgical debridement is not available or cannot be performed. Maggot therapy has been used in the treatment of pressure ulcers [73,74], chronic venous ulceration [75-78], diabetic foot ulcers [79,80], and other chronic wounds [81]. The larvae can be placed directly into the wound or applied within a prefabricated "biobag" (picture 1).

The larvae secrete proteolytic enzymes that liquefy necrotic tissue, which is subsequently ingested while leaving healthy tissue intact. Basic and clinical research suggests that maggot therapy has additional benefits, including antimicrobial action and stimulation of wound healing [75,82-84]. Maggot therapy may also reduce the duration of antibiotic therapy in some patients [85]. A systematic review demonstrated that maggot therapy facilitated faster and more effective debridement of non-viable tissue. There was increased development of granulation tissue and reduction in the wound surface area compared with hydrogel dressings. However, maggot therapy did not affect the complete wound healing [86].

A main disadvantage of maggot therapy relates to negative perceptions about its use by patients and staff. Other concerns are the cost, the requirement of communication between the hospital and laboratory to ensure maggot viability during transport, and the disposal of the biobag [87-89].

Autolytic — Autolytic debridement is a selective and conservative method of wound cleansing that uses endogenous enzymes in the wound to break down necrotic tissue, such as slough and eschar. This process is facilitated by maintaining a moist wound environment, typically achieved through the application of moisture-retentive dressings such as films [90]. Autolytic debridement is a slower process compared with other debridement methods but is generally considered less painful and well-tolerated by patients.

Adjunctive therapies

Negative pressure wound therapy — NPWT refers to wound dressing systems that continuously or intermittently apply subatmospheric pressure to the surface of a wound. Computational modeling has demonstrated that continuous delivery of pressure >40 mmHg is necessary for fibroblast migration in wound healing [91]. NPWT promotes the development of granulation tissue to cover deeper exposed tissues [92]. Information regarding the mechanism of action and use of this device and contraindications (eg, malignancy in the wound) is reviewed elsewhere. (See "Negative pressure wound therapy".)

NPWT is primarily used in situations where healing is expected; however, NPWT may improve the healing of some types of chronic wounds/ulceration, provided they are well vascularized [61,93-97]. Patients with extremity wounds and inadequate peripheral pulses should undergo noninvasive vascular testing to confirm adequate perfusion prior to instituting NPWT, especially patients with diabetes or other risk factors for peripheral artery disease. (See "Noninvasive diagnosis of upper and lower extremity arterial disease".)

Single-use NPWT is a small, ultraportable device that is an alternative to traditional NPWT. Single-use NPWT overcomes barriers to NPWT, such as large size, challenges with portability, and time and training needed for clinical device application. However, the device delivers commonly at lower pressures and is limited by the amount of fluid that the device can collect. Despite the lack of large clinical trials, single-use NPWT is promising in the care of pediatric burns [98]. In one randomized trial, closure was improved for single-use NPWT compared with traditional NPWT in patients with diabetic foot ulcers and venous leg ulcers (45 versus 22.2 percent, respectively) [99].

Most studies evaluating NPWT focus on particular wound types. Most studies are small, have methodologic flaws, and are at moderate-to-high risk of bias [100,101].

●NPWT reduces the time to closure of diabetic foot ulcers and wounds resulting from diabetic foot surgery. In this population of patients, NPWT is also associated with shorter lengths of hospitalization, decreased complication rates, and reduced costs [102]. The use of NPWT in the management of diabetic foot lesions is discussed in detail separately. (See "Local care of diabetic foot ulcers", section on 'Role of negative pressure wound therapy'.)

●Trials have evaluated the use of NPWT as an adjunctive therapy for the management of pressure-induced skin and soft tissue. A systematic review and meta-analysis demonstrated a significant positive effect of the NPWT on chronic wound healing with decreased exudate, edema, and increased granulation tissue [103]. In patients with pressure injuries, NPWT expedites the reduction in pressure-induced injury size and severity of pressure-induced injury and reduces pain and dressing change times [100]. (See "Local care of pressure-induced skin and soft tissue injury".)

●A systematic review and meta-analysis of comparative studies of negative pressure wound therapy with instillation of a topical solution and dwell time (NPWTi-d) demonstrate a faster closure rate with a statistically significant reduction in bacterial count from the control groups using NPWT [104]. An additional systematic review demonstrated lower complications and shorter hospital stays in traumatic/orthopedic injuries despite the different topical instillation solutions used [105]. While some topical solutions used saline, most used an antiseptic solution such as sodium hypochlorite (0.4 to 0.5 percent) or antimicrobial agents.

Oxygen therapy — Wounds require a tissue oxygen tension of at least 20 mmHg to heal. Nonhealing wounds have lower oxygen tensions [106]. When chronic wounds suffer from hypoxia, the mitochondria catalyze the release of reactive oxygen species (ROS) [107]. ROS is involved in the regulatory process of the wound healing repair phases, as well as regulating the formation of new blood vessels (angiogenesis) at the wound site [108]. ROS burst helps aid in reducing pathogens present in wounds [108]. Hypoxia-inducible Factor 1, a complex of proteins, is also activated in hypoxic conditions and involved in the regulation of stem cells and growth factors such as vascular endothelial growth factor, platelet-derived growth factor, and stromal cell-derived factor (SDF) [109].

Hyperbaric oxygen therapy — Hyperbaric oxygen therapy (HBOT) is used as an adjunct to wound care in the treatment of chronic wounds [110-116]. HBOT consists of administering 100 percent oxygen at an increased pressure (2 to 3 atmospheres) in a chamber for usually 90 minutes. Increased oxygen levels in the blood saturate the plasma and tissue. Approved indications by Undersea Hyperbaric Medical Society related to wounds include diabetic foot ulcer, radiation injury (osteoradionecrosis including soft tissue), acute ischemia (air embolism, crush injury, peripheral), severe anemia, infections (gas gangrene, intracranial abscess, necrotizing soft tissue infections, refractory osteomyelitis), compartment syndrome, thermal burns, and compromised flaps. (See "Hyperbaric oxygen therapy" and "Management of late complications of head and neck cancer and its treatment", section on 'Hyperbaric oxygen'.)

Topical oxygen — Topical oxygen therapy provides localized oxygen delivery directly to the wound bed and periwound surfaces. Topical oxygen therapy is administered in two main ways:

●Intermittent oxygen therapy –This method follows a schedule akin to HBOT with 90-minute sessions, three to five times weekly or continuously, 24 hours a day, seven days a week. Intermittent topical oxygen therapy delivers concentrated oxygen (around 93 percent) at pressures slightly above atmospheric, typically below 1.1 atmospheres, directly to the area around the wound. This is achieved using a high-flow oxygen concentrator and a sealed bag or chamber.

●Continuous oxygen therapy – In contrast, continuous topical oxygen therapy involves direct application of pure (>99 percent), humidified oxygen to the wound, supplied by a small, portable electrochemical oxygen generator. While all these technologies utilize oxygen to facilitate wound healing, the amount of oxygen reaching the wound is determined by several key factors: pressure, concentration, therapy duration, and the method of application [61].

Topical oxygen therapy may have a positive effect on wound healing compared with standard care [117]. Systematic review and meta-analysis of localized oxygen delivery to the wound bed in patients with Wagner 1 or 2 diabetic foot ulcers (superficial) enhance healing in hypoxic wounds [118]. However, there remains a lack of randomized trials for other wound etiologies [117]. The use of topical oxygen as an option is being explored for those patients who are not candidates for HBOT and other applications in wound healing.

WOUND DRESSINGS — 

Following debridement, a suitable dressing is applied to the wound and changed appropriately to maintain an optimal healing environment. In addition, wounds must be continually monitored as their characteristics and dressing requirements change over time [119].

No single dressing is perfect for all wounds; rather, a clinician should evaluate the wounds and choose the best dressing on a case-by-case basis. A detailed description of common, differing types of wounds and potential dressings is provided in the tables. Some dressings may have additional benefits in terms of local antimicrobial effects, reduced pain on change, odor control, and anti-inflammatory or mild debridement ability. These benefits are secondary to the primary function of the dressing in maintaining a moist but not excessively moist environment and protecting the wound. (See "Principles of acute wound management", section on 'Ideal dressing characteristics'.)

Selection and frequency — The moisture content of a wound bed must be kept in balance. A dressing should keep the wound moist enough to promote healing, but excess exudate must be absorbed away from the wound to prevent maceration of the healthy tissue.

There is little clinical evidence to aid in the choice between the different types of wound dressings in the management of chronic wounds. Consensus opinion supports the following general principles for chronic wound management [120].

●Hydrogels for the debridement stage (See 'Hydrocolloids, hydrogels, and hydroactive' below.)

●Low-adherent dressings that maintain moisture balance for the granulation stage

●Low-adherent dressings for the epithelialization stage

The advantages and disadvantages of the various dressing types are discussed below. (See 'Common dressings' below.)

Some dressings impede some aspects of wound healing; they should be used with caution. As an example, alginate dressings with high calcium content may impede epithelialization by triggering premature terminal differentiation of keratinocytes [121], and highly silver-containing dressings are potentially cytotoxic and should not be used in the absence of significant infection. (See 'Films foams and alginates' below and 'Topical antiseptics and antimicrobial agents' below.)

Dressings are typically changed once a day or every other day to avoid disturbing the wound-healing environment. The degree of drainage/moisture should help guide the clinician in terms of dressing selection and frequency. Some chronic wounds (eg, chronic venous ulcers) can have copious amounts of drainage and require more frequent dressing changes. Excessive moisture is detrimental, leading to maceration of the wound and surrounding skin.

Common dressings — Dressings can be categorized by their water-retaining abilities as open, semi-open, or semi-occlusive. (See "Principles of acute wound management", section on 'Dressing types'.)

●Open – Open dressings include primarily gauze, which is typically moistened with saline before placing it into the wound. Gauze dressings are inexpensive but often require frequent dressing changes. Wet-to-moist gauze dressings are useful for packing large soft-tissue defects until wound closure or coverage can be performed (eg, pressure-induced injury). (See "Principles of acute wound management", section on 'Open'.)

●Semi-open – Semi-open dressings generally do not maintain a moisture-rich environment or provide good exudate control. These dressings may have specific uses, often in postoperative wounds (eg, Xeroform over burn wound harvest area). (See "Principles of acute wound management", section on 'Semi-open'.)

●Semi-occlusive – Semi-occlusive dressings are often used in the management of chronic wounds and come in a wide variety of occlusive properties, absorptive capacities, conformability, and bacteriostatic activity (table 2). Semi-occlusive dressings, such as films, foams, alginates, hydrocolloids, and hydrogels, are frequently used to manage chronic wounds and are discussed in detail below.

Films foams and alginates

●Films – Polymer films are transparent sheets of synthetic self-adhesive dressing that are permeable to gases such as water vapor and oxygen but impermeable to larger molecules, including proteins and bacteria. This property enables insensible water loss to evaporate, traps wound fluid enzymes within the dressing, and prevents bacterial invasion.

•Advantages include their ability to maintain moisture, encourage rapid re-epithelization, transparency, and self-adhesive properties.

•Disadvantages include limited absorptive capacity. They are not appropriate for moderate to heavily exudative wounds. If they are allowed to remain in place over a wound with heavy exudates, the surrounding skin is likely to become macerated. In addition, if the wound dries out, film dressings may adhere to the wound and be painful and damaging to remove.

●Foams – Foam dressings can be thought of as film dressings with the addition of absorbency. They consist of two layers, a hydrophilic silicone or polyurethane-based foam that lies against the wound surface and a hydrophobic, gas-permeable backing to prevent leakage and bacterial contamination. Some foams require a secondary adhesive dressing.

•Advantages include their high absorptive capacity and the fact that they conform to the shape of the wound and can be used to pack cavities.

•Disadvantages include the opacity of the dressings and the fact that they may need to be changed each day. Foam dressings may not be appropriate on minimally exudative wounds, as they may cause desiccation.

●Alginates – Natural complex polysaccharides from various types of algae form the basis of alginate dressings. Their activity as dressings is unique because they are insoluble in water, but in the sodium-rich wound fluid environment, these complexes exchange calcium ions for sodium ions and form an amorphous gel that packs and covers the wound. Alginates come in various forms, including ribbons, beads, and pads. Their absorptive capacity ranges depending upon the type of polysaccharide used. In general, these dressings are more appropriate for moderately to heavily exudative wounds.

•Advantages include augmentation of hemostasis [122], they can be used for wound packing, most can be washed away with normal saline to minimize pain during dressing changes, and they can stay in place for several days.

•Disadvantages are that they require a secondary dressing that must be removed to monitor the wound, they can be too drying on a minimally exudative wound, and they have an unpleasant odor.

Although petroleum jelly aids as a moisturizer, alginates may incite better granulation tissue in patients with diabetic foot ulcers [123]. In a trial of 77 patients, patients with diabetic foot wounds were randomly assigned to alginate or petroleum gauze dressings [124]. Patients treated with alginates had significantly superior granulation tissue coverage at four weeks of treatment, significantly less pain, and fewer dressing changes than the petroleum gauze group.

Hydrocolloids, hydrogels, and hydroactive

●Hydrocolloids – Hydrocolloid dressings usually consist of a gel or foam on a carrier of self-adhesive polyurethane film. The colloid composition of this dressing traps exudate and creates a moist environment. Hydrocolloid products include DuoDERM, Tegasorb, Johnson and Johnson Ulcer Dressing, and Comfeel.

•Advantages are that bacteria and debris are trapped and washed away with dressing changes in a gentle, painless form of mechanical debridement. Another advantage of hydrocolloids is the ability to use them for packing wounds.

•Disadvantages include malodor, the potential need for daily dressing changes, and possible allergic contact dermatitis [125]. Iodine-induced hyperthyroidism has been documented with the use of cadexomer iodine for leg ulcers [126].

Cadexomer iodine is a type of hydrocolloid in which iodine is dispersed and slowly released after it comes in contact with wound fluid. The concentration of iodine released is low and does not cause tissue damage [127].

●Hydrogels – Hydrogels are a matrix of various types of synthetic polymers with >95 percent water formed into sheets, gels, or foams that are usually sandwiched between two sheets of removable film. The inner layer is placed against the wound, and the outer layer can be removed to make the dressing permeable to fluid. Sometimes, a secondary adhesive dressing is needed. These unique matrices can absorb or donate water depending upon the hydration state of the tissue that surrounds them. Hydrogels are most useful for dry wounds.

•An advantage is that they initially lower the temperature of the wound environment they cover, which provides cooling pain relief for some patients [128].

•A potential disadvantage, although there have been no reports of increased wound infection, is that hydrogels have been found to selectively permit gram-negative bacteria to proliferate [129].

●Hydroactive – Hydroactive is a polyurethane matrix that combines the properties of a gel and a foam. Hydroactive selectively absorbs excess water while leaving growth factors and other proteins behind [130].

A randomized trial compared hydroactive dressings with two different hydrocolloids and found the hydroactive dressing to be equally effective at promoting ulcer healing and alleviating ulcer-associated pain after 12 weeks of treatment [131]. Another study reported that hydroactive dressings combined with enzymatic debridement were more cost-effective than gauze alone in dressing pressure ulcers and venous stasis ulcers [132].

Topical therapies — After appropriately addressing debridement of necrotic tissue, pressure offloading, infection, and ischemia, several adjunctive therapies may be helpful to augment wound healing.

Topical antiseptics and antimicrobial agents — Some topical antimicrobials may be associated with potential benefits in selected patient populations. The properties of some broadly used agents are reviewed below; others are reviewed separately (table 2). (See "Topical agents and dressings for local burn wound care".)

●Iodine-based – Cadexomer iodine (eg, Iodosorb) is an antimicrobial that reduces bacterial load within the wound and may support healing by providing a moist wound environment [127]. Cadexomer iodine is bacteriocidal to all gram-positive and gram-negative bacteria. For topical preparations, there is some evidence to suggest that cadexomer iodine generates higher healing rates than standard care but should likely only be considered for use on a short-term basis.

A multicenter trial reported that over 12 weeks, cadexomer iodine paste was more cost-effective than non-iodinated hydrocolloid dressing or paraffin gauze dressing in patients with exudating venous ulcers [133]. A systematic review found some evidence that topical application of cadexomer iodine enhanced venous ulcer healing rates compared with standard care (with and without compression) [134]. The treatment regimen was complex, and it is unclear if the results are generalizable to most clinical settings.

●Silver-based – Silver is toxic to bacteria and silver-containing dressings are used by many clinicians to decrease heavy bacterial surface contamination [127]. However, a systematic review and meta-analysis of silver dressings used in diabetic foot ulcer demonstrated improved healing rate, shortened time to complete healing, shortened in-hospital duration, and improved infection resolution rate. However, there was no significant effect on the reduction of ulcer area [135].

●Honey – Honey has been used since ancient times for the management of wounds. Honey has broad-spectrum antimicrobial activity due to its high osmolarity and high concentration of hydrogen peroxide [136]. Medical-grade honey products are now available as a gel, paste, and impregnated into adhesive, alginate, and colloid dressings. Systematic reviews demonstrate that honey promotes healing, epithelialization, and wound contraction [136]. Additionally, honey had an anti-inflammatory and autolytic debridement effect, decreasing pain, infection control, and was cost-effective [137].

Growth factors — Growth factors important for wound healing include platelet-derived growth factor (PDGF), fibroblast growth factor, and granulocyte-macrophage colony-stimulating factor (GM-CSF), amongst others. (See "Basic principles of wound healing".)

Recombinant human growth factors have been developed and are being actively investigated for the treatment of chronic ulcers, mostly those affecting the lower extremities. As with other therapies, isolated growth factors applied in the absence of good-quality debridement, infection control, and offloading when indicated are likely to be ineffective in promoting healing [138,139].

Becaplermin is a PDGF gel preparation that promotes cellular proliferation and angiogenesis and thereby improves wound healing [140]. It is approved for use in the United States as an adjuvant therapy for the treatment of diabetic foot ulcers and is the only pharmacologic agent approved for the treatment of chronic wounds.

Wound packing — Packing chronic wounds associated with significant dead space, tunneling, or undermining is important to reduce physiological dead space, absorb exudate/seroma collection, and reduce the potential for infection. Wound packing and materials are discussed separately. (See "Principles of acute wound management", section on 'Wound packing'.)

Specific chronic wound issues — Local wound care of chronic wounds is also directed toward dealing with the troublesome chronic wound problems that affect the patient physically and emotionally, such as excess exudate that can lead to unpleasant odors, pain and itching, and bleeding from the wound.

Odor — Wound odor can be controlled with interval mechanical debridement to decrease the microbial bioburden on the wound surface, with topical antimicrobial therapy (eg, metronidazole) [141-143] and/or with odor-absorbing dressings such as those that have absorptive charcoal within the dressing for palliative or malignant fungating wounds [144] Soaks of dilute acetic acid, polyhexamethyl biguanide hypochlorous acid, or Dakin solution can also help to minimize odor [144]. Long-term frequent use of potentially locally cytotoxic agents such as Dakin solution is not recommended.

Bleeding — A nonadherent dressing can be placed directly on the friable wound to reduce bleeding and reduce pain associated with dressing changes. A second layer of alginate dressings that contain coagulants can also help to minimize bleeding.

Chronic wounds that are prone to oozing from the ulcer bed (eg, malignant wounds that cannot be excised) can be controlled with topical hemostatic agents or calcium alginate [144] and gentle pressure in the form of elastic bandages, with focal points of bleeding managed with silver nitrate, handheld cautery, or local anesthetic with epinephrine. (See "Overview of topical hemostatic agents and tissue adhesives" and "Subcutaneous infiltration of local anesthetics".)

Pruritus — Itching can be a complaint with chronic wounds. Itching and irritation are usually due to dry or wet skin or contact dermatitis. Keeping a proper moisture balance and protecting the skin will help reduce itching and skin irritation, and, if necessary, topical corticosteroid creams can be applied. (See "Irritant contact dermatitis in adults", section on 'Management'.)

Exudate — An absorptive dressing should be placed over the nonadherent dressing to control drainage, reduce periwound maceration, and control the amount of exudate in the wound, and should be tailored to the specific anatomic location and wound depth (table 3). Superabsorbent wound dressings have been beneficial for moderate to highly exudating chronic leg ulcers [145,146]. Alternatively, wound drainage can be drawn away using a collecting device (eg, ostomy appliance, negative pressure wound therapy device), provided there are no contraindications.

WOUND COVERAGE/CLOSURE — 

Surgical procedures that provide wound coverage/closure are briefly described below. It is important to address the underlying etiology of the wound prior to performing the definitive procedure to minimize the risk of recurrence. Recurrence of the wound at the same site or development of wounds at another location can occur after initial healing, especially in high-risk patients. As an example, patients with diabetes with peripheral neuropathy must be adequately protected with specialized accommodative inserts, shoes, and braces. Thus, careful follow-up is needed. (See 'General care' above.)

If the wound is relatively small, it can be completely excised and closed primarily (sutures/staples), provided there is no to minimal skin tension. An understanding of appropriate tension and blood supply is paramount to allow for healing. In a previously infected wound, we avoid placing absorbable sutures deeply within the wound. In this situation, vertical mattress sutures may help bring the deep and superficial spaces together.

Larger or more complicated wounds may require graft or flap coverage. These can be done once a layer of healthy granulation tissue has developed at the base of the wound. Procedures that provide coverage for chronic wounds are listed below and discussed in more detail in the linked topics.

●Split-thickness skin graft – Split-thickness skin grafts (STSGs), also called partial-thickness grafts, are autologous epidermal/dermal grafts. Chronic wounds with a good bed of granulation tissue and without exposed tendons or bone are good candidates for skin grafting. STSGs may be complicated by secondary contracture and should be avoided in areas around joint surfaces. (See "Skin autografting", section on 'Split-thickness skin grafting'.)

●Full-thickness skin grafts – Full-thickness skin grafts (FTSGs) are autologous epidermal and full-thickness dermal grafts. These grafts have a decreased incidence of secondary contracture. FTSG is appropriate when a thicker autograft is necessary, such as for deeper wounds or in areas that require more durable tissue (eg, foot). (See "Skin autografting", section on 'Full-thickness skin grafting'.)

●Xenografts/allografts – If an autologous graft is not possible, a xenograft or allograft can be used. The various types of skin substitutes, their classification, and their uses are reviewed separately. (See "Skin substitutes".)

One strategy is to use a xenograft or allograft to build up a dermal tissue layer prior to STSG application. The xenograft or allograft will be replaced by the host tissue over time. There are a variety of xenografts/allografts that serve different purposes. Porcine epidermis can be applied to the wound surface as a test to ensure that adequate debridement was performed prior to the definitive closure/coverage procedure, or it can be used as a biologic dressing when there is low confidence in patient compliance. Other xenografts, including bovine collagen, can be used to cover deeper soft tissue defects to form a neodermis in preparation for receiving a split-thickness skin graft. Allografts can be used for the same purpose.

●Local tissue flaps – Local tissue rearrangement is useful in many circumstances when primary closure is not possible. These techniques involve the recruitment of skin from surrounding areas and transposing it into the defect to allow for closure. Blood supply to the flap must be preserved. Common local tissue flaps include V-to-Y advancement, rotation flaps, and advancement flaps. (See "Z-plasty" and "Overview of flaps for soft tissue reconstruction", section on 'Skin'.)

●Pedicled flaps – Pedicled flaps are useful when muscle or fascia is needed to cover a large wound or deep wound that has an exposed tendon or bone. The blood supply to the harvested muscle must be preserved, and the flap is rotated to cover the wound defect. Pedicled flaps include expendable muscles, such as the abductor hallucis muscle flap for coverage of medial foot or ankle defects or the hemi-gastrocnemius muscle flap to cover knee defects. Another common flap is the soleus flap for coverage of mid-tibial defects. (See "Surgical reconstruction of the lower extremity" and "Overview of flaps for soft tissue reconstruction", section on 'Pedicled'.)

●Free tissue transfers – Free tissue transfer is an important technique for the closure of larger soft tissue defects that may not be amenable to pedicled or local advancement flaps. The muscle or fascia is harvested, with or without the overlying skin, along its vascular pedicle. The free flap is placed into the defect, and the arterial and venous blood supply is sutured to a local artery and vein nearby. (See "Overview of flaps for soft tissue reconstruction", section on 'Skin'.)

SPECIFIC TYPES OF CHRONIC WOUNDS — 

The management of specific chronic wounds is briefly discussed below.

●Diabetic foot ulcers – Diabetic foot ulcers are a unique category of chronic wounds that require multiple considerations (algorithm 1). The treatment of diabetic foot ulcers is discussed separately. (See "Local care of diabetic foot ulcers".)

●Ischemic ulcers and gangrene – The presence of ischemia influences the timing of revascularization, debridement, and definitive coverage/closure. For patients with chronic limb-threatening ischemia, revascularization will be necessary before there can be any expectation of wound healing [147]. (See "Management of chronic limb-threatening ischemia".)

●Chronic orthopedic wounds – Large soft tissue defects of the extremities are often the result of trauma and are frequently accompanied by bony fractures. When traumatic wounds become chronic, wound coverage options are dictated by the severity of the initial injury and the anatomic location The skeletal framework must be addressed to provide stability of the overlying soft tissue envelope. . (See "Severe lower extremity injury in the adult patient" and "Surgical reconstruction of the lower extremity".)

For traumatic wounds that require internal fixation, the chronicity of the wound may be due to an underlying bone infection (osteomyelitis) or biofilm on a screw, plate, anchor, or heavy suture. Thus, the removal of affected materials will be necessary for definitive closure. Bone infection requires resection of the infected segment and long-term antibiotics. Treatment of chronic or subacute osteomyelitis can last weeks to months, followed by a period off of antibiotics, after which time bone culture is repeated. If the repeat culture or aspirate is negative, definitive soft tissue closure/coverage can proceed. (See "Osteomyelitis in the absence of hardware: Approach to diagnosis in adults".)

Total joint implants pose a difficult problem. Expeditious soft tissue coverage or closure over noninfected joint implants or internal fixation is important. Infected internal fixation constructs and joint implants may require removal with subsequent reimplantation once the infection is resolved. Typically, these problems require pedicled flaps or free tissue transfers for definitive coverage. (See 'Wound coverage/closure' above and "Skin autografting" and "Surgical reconstruction of the lower extremity".)

●Abdominal wounds – A chronic open abdominal wound can occur following local skin separation, partial fascial dehiscence, or complete fascial dehiscence, leading to evisceration from an abdominal incision. More often, open abdominal wounds result from intentionally leaving an abdominal incision open at the completion of an abdominal procedure to prevent abdominal compartment syndrome. Rarely, large defects are the result of traumatic injury (eg, shotgun blast).

If the wound is small and the fascia is intact, local wound care with bedside incision and drainage may be all that is needed. Negative pressure wound therapy (NPWT) can aid in the closure of clean abdominal wounds. For larger wounds, those that have drainage, and those with abdominal wall necrosis, surgical debridement, and sequential second-look procedures are more optimal for achieving definitive closure. (See "Surgical management of necrotizing soft tissue infections" and "Management of the open abdomen in adults".)

The following case examples illustrate different types of chronic abdominal wounds.

•The pictures in the figure show the management of a patient with a necrotizing abdominal wall infection related to a surgical site infection. Following debridement of infected and necrotic material (picture 2), including the fascial edges, the wound was able to be closed primarily.

•The pictures in the figure show the management of a child with a nonhealing abdominal wall wound that was present for five months (picture 3). The wound was treated with open dressings until a bed of granulation tissue was present, after which a xenograft was initially placed to ensure that a skin graft would be taken. NPWT was used to secure the xenograft. A skin graft was placed five days later with a good result.

●Pressure-induced skin and soft tissue injury – Pressure-induced injury is due to chronic pressure in susceptible areas that leads to ischemia and skin loss. The treatment of pressure ulcers depends upon the stage of the ulcer. (See "Local care of pressure-induced skin and soft tissue injury" and "Surgical management of pressure-induced skin and soft tissue injuries".)

●Ulcerated and fungating malignancy-related wounds — The palliative treatment of malignancy-related (eg, post-radiation therapy) or ulcerating or fungating malignant wounds represents a clinical challenge without evidence-based guidelines or established protocols. The clinician should establish goals for wound management with the patient.

Chronic wounds related to malignancy require appropriate treatment of the malignancy. Although symptom management strategies for comfort may work in tandem with healing interventions with the goal of eventual wound closure, it is important to recognize when efforts toward wound closure may become unrealistic or burdensome for the patient. In some cases, palliation may be all that can be offered. (See "Overview of the care of adult patients with nonhealable wounds".)

●Venous stasis ulcers – The mainstay of treatment for venous ulceration is local wound care and compression therapy. Skin grafting may improve ulcer healing and is indicated for those who do not exhibit appropriate wound healing after 12 months of medical care. (See "Evaluation and management of chronic venous insufficiency including venous leg ulcer", section on 'Ulcer care'.)

WHEN TO REFER THE PATIENT TO A WOUND SPECIALIST — 

While many chronic wounds can be effectively managed in the primary care setting or by clinicians with general wound care expertise, there are specific situations where referral to a wound specialist is strongly recommended. Wound care specialists are part of an interdisciplinary team of specialists that orchestrate the patient's next best steps in helping to heal a hard-to-heal wound. Early identification of complex or non-responsive wounds and timely referral can significantly improve patient outcomes, reduce the risk of complications, and optimize resource utilization. Referral should be considered in the following circumstances:

●Lack of progress despite optimal management – If a chronic wound fails to demonstrate significant improvement, usually a 40 to 50 percent reduction in wound size within four weeks. This includes wounds that are not decreasing in size, continue to exhibit significant exudate, or show no improvement in granulation tissue [148].

●Complex wound characteristics – Certain wound characteristics indicate a higher risk of complications and often require specialized expertise.

●Deep wounds – Wounds extending into subcutaneous tissue, muscle, or bone.

●Wounds with exposed bone or tendon – These wounds are at increased risk of infection and require advanced management strategies or surgical flaps [149].

●Wounds with undermining or tunneling – These features can be difficult to assess and treat effectively without specialized knowledge [150].

●Wounds with significant pain – Uncontrolled pain despite appropriate topical or oral analgesia may indicate underlying complications or the need for advanced pain management strategies, as well as greater control of possible infection in patients who do not demonstrate neuropathy [151].

●Wounds with signs of infection that are not responding to initial treatment – This includes spreading cellulitis, systemic signs of infection (fever, chills), or suspicion of deep tissue infection. In these circumstances, hospitalization may be suggested.

●Underlying medical conditions complicating wound healing – Certain medical conditions can significantly impair wound healing and necessitate specialized care.

●Uncontrolled diabetes mellitus – Poor glycemic control is a major risk factor for chronic wounds and can significantly hinder healing.

●Peripheral arterial disease with chronic limb-threatening ischemia – These wounds often require vascular evaluation and intervention in addition to specialized wound care [152].

●Venous insufficiency with significant edema and ulceration – Complex venous ulcers may benefit from early diagnostic testing and intervention. Early endovenous ablation in patients demonstrating significant venous insufficiency has demonstrated improvement in wound healing [153]. Specialized compression therapy, skin substitutes, and other advanced treatments may help improve wound healing. ¹⁰⁷

●Immunocompromised states – Patients with conditions like human immunodeficiency virus, acquired immunodeficiency syndrome, those on immunosuppressive medications, or those undergoing chemotherapy are at higher risk of infection and delayed healing.

●Wounds in difficult locations – Wounds located in certain areas can be particularly challenging to manage and may benefit from specialist input.

●Wounds on the foot, especially in patients with diabetes – These wounds are at high risk of infection and amputation [152].

●Wounds located near major joints or pressure points – These wounds are subject to repetitive trauma and/or pressure and may require specialized offloading strategies [154].

●Need for advanced wound therapies – Certain wound therapies require specialized training and may not be available in all settings. Referral is necessary when advanced therapies such as negative pressure wound therapy (NPWT), bioengineered skin substitutes, oxygen therapy, or surgical debridement are being considered.

●Diagnostic uncertainty – If the cause of the chronic wound is unclear or if a definitive diagnosis has not been established, referral for further evaluation, including potential biopsies or specialized imaging, is warranted.

●Patient adherence factors and preferences – In some cases, patient factors such as complex social situations, limited access to resources or transportation, or strong patient preference may warrant referral to a wound specialist who can provide comprehensive care and referral for wound care supplies and devices such as specialized mattresses and hospital beds provided by the durable medical equipment supplier. Additionally, home care services can be prescribed to continue the communication with the wound provider [148].

Emerging therapies

●Topical Beta-Blockers – Beta-adrenergic receptors in keratinocytes have been identified as playing a role in wound healing. Topical beta-blockers, such as timolol and esmolol, have shown promise in accelerating epithelialization and improving wound healing outcomes [155]. Some studies suggest that these agents enhance keratinocyte migration and proliferation, leading to faster wound closure. However, while early trials in diabetic foot ulcers have reported positive results, there is still a lack of large-scale randomized controlled trials to confirm their efficacy [156]. Further research is needed to determine the optimal dose and duration of treatment.

●Advanced biologic dressings – Recent advancements in wound care have led to the development of bioengineered skin substitutes, growth factor-infused dressings, and collagen-based scaffolds [157]. These products aim to provide a more favorable wound environment that stimulates tissue regeneration by providing an extracellular matrix, promoting wound healing. Some scaffolds also contain antimicrobial agents to help reduce bioburden [158-160]. Medicare outcomes analysis for venous leg ulcers revealed that patients who received cellular, acellular, and matrix-like product, compared with patients who received no advanced therapy, had the best outcomes [161-163]. Although initial studies indicate improved healing rates, challenges such as high costs, limited availability, and inconsistent outcomes remain barriers to widespread adoption. Additionally, the lack of standardized guidelines for selecting the appropriate type of therapy due to a paucity of comparative trials presents a gap in clinical practice.

●3D bioprinting and regenerative medicine – The application of 3D bioprinting technology in wound care is an emerging area of research. By using patient-derived cells to create customized skin grafts, this approach has the potential to revolutionize chronic wound management. Early-stage studies have demonstrated the feasibility of using bioprinted skin constructs for wound coverage, but clinical applications remain limited [164]. Further advancements in bioprinting techniques and long-term outcome studies are needed to establish its role in routine clinical practice.

●Gene therapy and stem cell treatments – Gene therapy and stem cell-based approaches have gained attention as potential solutions for nonhealing wounds. Mesenchymal stem cells and exosome therapy have shown promise in preclinical and early-phase clinical trials [165]. These therapies aim to promote angiogenesis, modulate inflammation, and accelerate tissue repair [166]. However, regulatory challenges, ethical considerations, and the need for long-term safety data pose significant barriers to clinical implementation.

●Smart wound dressings – Smart wound dressings embedded with sensors that monitor pH, moisture levels, and bacterial load offer the potential for real-time wound assessment [167]. While these technologies show promise, more clinical trials are needed to validate their effectiveness and determine their impact on standard wound care practices.

●Machine learning and artificial intelligence – Machine Learning models may predict chronic wound healing time by using clinical factors curated from the electronic health records as well as the wound measurements [168].

Evidence gaps in chronic wound care — Despite advances in wound care, several gaps in the evidence base remain:

●Comparative effectiveness of adjunctive therapies – There is a need for well-designed studies comparing topical oxygen, hyperbaric oxygen therapy (HBOT), NPWT, and biologic tissue-engineered dressings to establish the most effective treatment strategies.

●Comparative use of dressing application treatment – Comparative trials on the appropriate use of available dressing treatments, including the efficacy of hydrogels, alginates, and foams impregnated with different antimicrobial agents.

●Standardized biofilm management strategies – Chronic wounds often contain bacterial biofilms, yet there is no consensus on the most effective antimicrobial approaches.

●Palliative wound care guidelines – For patients with nonhealable wounds, a standardized approach to symptom management and quality-of-life considerations is needed.

●Integration of artificial intelligence and digital wound care – Artificial intelligence-driven wound assessment tools can potentially help improve outcomes. However, further validation is required to integrate these technologies effectively into clinical workflows.

●Comparative effectiveness – Randomized and comparative control trials are needed regarding adjunctive measures such as topical oxygen, HBOT, NPWT, and biologic tissue-engineered dressings.

Addressing patient concerns and enhancing adherence to wound care

●Effective wound management extends beyond the technical application of dressings and debridement techniques. It necessitates a holistic approach that acknowledges and addresses the patient's concerns, fosters a collaborative relationship, and promotes adherence to the treatment plan [169]. Neglecting these crucial aspects can significantly impede healing, increase the risk of complications, and negatively impact the patient's quality of life [170].

●Successful wound care is establishing open and honest communication with the patient. Chronic wounds can be a source of significant anxiety, pain, and social isolation. Patients may harbor fears about infection, amputation, or the prolonged nature of the healing process [171]. Clinicians must create a safe and empathetic environment where patients feel comfortable expressing their concerns and asking questions. Actively listening to the patient's perspective, validating their feelings, and providing clear, understandable explanations about their condition and treatment plan are essential for building trust and rapport [172].

●Addressing patient concerns proactively can also mitigate potential barriers to adherence. For instance, concerns about pain associated with dressing changes can be addressed by discussing pain management strategies, including pre-medication or alternative dressing techniques [173]. Practical concerns, such as the ability to manage dressings at home or financial limitations, also need to be explored and addressed. Connecting patients with resources like home health care services, support groups, or financial assistance programs can significantly improve their ability to follow the prescribed regimen [174].

●Patient education plays a pivotal role in fostering adherence. Patients who understand the rationale behind the treatment plan, the importance of specific interventions, and the potential consequences of non-adherence are more likely to actively participate in their care. Education should be tailored to the individual patient's needs and learning style, using clear language and visual aids when appropriate [175]. Demonstrating proper wound care techniques, explaining the signs of infection, and providing written instructions can empower patients to take ownership of their wound care.

●Creating a sense of partnership in the healing process is crucial. Involving patients in decision-making regarding their treatment, when possible, can increase their sense of control and motivation. Setting realistic goals together and celebrating small victories can further enhance engagement and adherence [176]. Regular follow-up appointments provide opportunities to assess progress, address any emerging concerns, and reinforce the importance of adherence [177].

●Finally, it is essential to recognize that adherence is not solely the responsibility of the patient. Clinicians must also ensure that the treatment plan is practical, feasible, and aligned with the patient's lifestyle and resources. Simplifying complex regimens, considering alternative treatment options when necessary, and providing ongoing support can significantly improve adherence rates [178].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Open wound management".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. 

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)

●Basics topics (see "Patient education: How to change a dressing (The Basics)" and "Patient education: Caring for an open wound (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Chronic wounds – A chronic wound may be defined as one that is physiologically impaired due to a disruption of the wound healing cycle. Some define a chronic state as a reduction of less than 15 percent of the surface area of the wound over one week or less than 50 percent over one month. Examples of chronic wounds include nonhealing or infected surgical or traumatic wounds, venous ulcers, pressure ulcers, diabetic foot ulcers, ischemic ulcers, and some malignancy-associated wounds. (See 'Introduction' above and 'Chronic wound state' above.)

●General care – General care of patients with chronic wounds includes local wound care as well as management of any underlying medical conditions contributing to the chronic wound state. In general, surgical intervention is necessary to manage the infection and prepare the wound bed for subsequent coverage/closure, which may require repeated procedures, and to handle any underlying factors that are contributing to the chronic wound state (eg, bony deformities, foreign body, biomechanical instability), and sometimes to restore adequate perfusion through revascularization. Underlying medical condition(s) contributing to the chronic wound must be evaluated and addressed prior to any planned definitive surgical procedure. (See 'General care' above.)

●Wound bed preparation – Local care of chronic wounds includes debridement and proper wound dressings.

•Debridement – For optimal wound healing, the wound bed should be well vascularized, free of devitalized tissue, clear of infection, and moist. For most patients with chronic wounds or ulcers, we suggest sharp surgical debridement over nonsurgical methods for the debridement of devitalized tissue (Grade 2C). When surgical expertise is not available or for selected patients for whom serial debridement may not be tolerated or who have barriers that limit frequent clinic visits, alternative methods include autolytic, mechanical, enzymatic, or biologic debridement. These may also be used between surgical debridement, as needed. (See 'Surgical excisional debridement' above.)

•Adjunctive therapies – Negative pressure wound therapy (NPWT) is frequently used to manage complex wounds and reduce the complexity of definitive closure. Other therapies, such as hyperbaric and topical oxygen, have been used with the aim of enhancing wound healing. Bioengineered skin substitutes, topical growth factors, and collagen matrices have also been demonstrated to increase wound healing rates. (See 'Adjunctive therapies' above.)

●Wound dressings – Wound dressings should be chosen based on their ability to manage dead space, control exudate, reduce pain during dressing changes (as applicable), prevent bacterial overgrowth, ensure proper fluid balance, be cost-efficient, and be manageable for the patient or nursing staff. Adjuncts to wound healing may include NPWT and hyperbaric oxygen therapy (HBOT), provided there are no contraindications for their use. (See 'Wound dressings' above.)

•Topical therapy – Topical agents such as antiseptics and antimicrobial agents can be used to control locally heavy contamination. Significant improvements in rates of wound healing have not been reported, and toxicity to the tissues might be a significant disadvantage. (See 'Topical therapies' above.)

•Specific chronic wound issues – Wound care should also be directed toward dealing with the most troublesome chronic wound problems that affect the patient physically and emotionally, such as odor, bleeding, itching, excess exudate, pain, and minimizing infection. (See 'Specific chronic wound issues' above.)

●Wound coverage/closure – Following wound bed preparation, chronic wounds that demonstrate progressive healing as evidenced by granulation tissue and epithelialization along the wound edges can undergo delayed closure or coverage with skin grafts or bioengineered tissues. (See 'Wound coverage/closure' above.)

•Limited chronic wounds may be amenable to complete excision and primary closure (sutures/staples), provided there is no to minimal skin tension.

•Larger or more complicated chronic wounds may require coverage using a skin graft or skin/muscle flap.

●Follow-up care – Once a chronic wound has been closed or covered, clinical follow-up and wound surveillance are necessary. Wounds can recur after initial healing, particularly in high-risk populations, such as in patients with diabetic foot wounds. To prevent recurrence, it is important to address the factors that were responsible for the development of the wound.

●Specific chronic wounds – The management of specific chronic wounds, diabetic foot wounds, chronic orthopedic wounds, chronic abdominal wounds, pressure ulcers, ulcerated and fungating malignancy-related wounds, and venous ulcers is briefly reviewed in this topic. (See 'Specific types of chronic wounds' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Paul J Kim, DPM, MS, who contributed to earlier versions of this topic review.