Water is absolutely vital to wound healing. Clinical dehydration is defined as a 1 % decrease in body weight due to fluid loss. Healthy individuals with open wounds need 30–35 ml of water per kilogram of body weight daily. Patients with large wounds or burns may need even more. Patients on air-fluidized beds for severe pressure ulcers require 40–60 ml of water per kilogram of body weight daily.

Protein is required for tissue repair and regeneration. Without adequate protein stores, collagen synthesis, granulation tissue formation, angiogenesis, and remodeling are all significantly impaired. Normal immune functions, such as phagocytosis and antibody response time, are also hindered by low protein intake. Osmotic pressure is altered, and edema prevents oxygen’s ability to diffuse into affected areas, allowing accumulation of metabolic waste products. Although the main cause of protein deficiency is inadequate protein intake, patients may lose a significant amount of proteins through wound drainage. Since proteins consist of 16 % nitrogen, nitrogen excretion can be used as an indicator of protein intake. If excreted nitrogen exceeds the amount of ingested nitrogen in the form of proteins, the patient has a negative nitrogen balance. Ideally, patients should maintain a positive nitrogen balance to enhance wound healing.

Carbohydrates, primarily in the form of glucose, provide energy needed for tissue repair and regeneration. Carbohydrates demonstrate the protein-sparing effect. Therefore, adequate carbohydrate intake is imperative to maximize wound healing.

Fat is essential to the healing process. Most importantly, fat provides a needed energy source to fuel cellular processes when carbohydrates are depleted. Fat is also required to carry fat-soluble vitamins including vitamin A, E, and K and assists with thermoregulation.

Fats, in the form of free fatty acids, are vital components of the cell membrane and are required in the synthesis of new cells.

Vitamins are organic compounds that are needed in small amounts to build new tissues, to maintain tissue health, and to aid in normal immune functions. Vitamins A, C, E, K, and the B complex vitamins are especially important for wound healing. Vitamin A or retinol is a fat-soluble vitamin that maintains healthy skin and epithelial integrity. Vitamin A is required for collagen synthesis, promotes granulation tissue formation, and facilitates epithelialization. Vitamin A may be particularly important for individuals taking corticosteroids, since vitamin A can reverse inhibitory effects of long-term corticosteroids. Vitamin A supplements may also increase wound tensile strength. Topical and systemic supplementations are effective. Vitamin C or ascorbic acid is needed to build and maintain tissues, help body absorb iron, and produce collagen. Vitamin C may help to control infections by activating white blood cells. It is also an antioxidant and therefore may limit the damaging effects of free radicals. Pretreatment of irradiated skin with vitamin C may limit skin damage. Vitamin K is a fat-soluble vitamin that is essential for blood clotting. Due to its effect on clotting factors, deficiencies may lengthen the inflammatory phase of wound healing. The B complex vitamins are a group of eight water-soluble vitamins that are required for normal immune function and energy metabolism. The B complex vitamins aid in white blood cell function, antibody formation, and resistance to infection. They also facilitate fibroblast function and collagen synthesis. Vitamin E is a fat-soluble vitamin that helps prevent free radical-related cellular damage. Vitamin E decreases the inflammatory phase of wound healing, enhances immune function, and decreases platelet adhesion.

Microminerals (zinc, iron, copper, and magnesium) as well as macrominerals (calcium and phosphorous) are also important for the wound healing process. The skin contains 20 % of the body’s stores of zinc. Zinc is vital to many cellular processes including collagen and protein synthesis, cell proliferation, epithelialization, and normal immune function. Zinc, like vitamins C and E, is an antioxidant and may enhance wound healing by reducing the number of free radicals. Iron is an essential component of hemoglobin and is required for oxygen transport. It is also required for antibody production and normal immune functioning. Iron is a cofactor in many enzyme systems and is required for collagen and DNA synthesis. Anemia may lead to tissue hypoxia, decreased immune function, decreased cell replication, and decreased wound tensile strength. The mineral copper is required for hemoglobin synthesis and iron absorption and transport. Copper also helps to increase the strength of collagen cross-links. Deficiencies may lead to poor wound healing and decreased immune function. Magnesium deficiency is often found in patients with diabetes, alcoholism, chronic diarrhea, or dehydration. Inadequate stores of magnesium lead to hypertension and vasoconstriction. Calcium is an essential factor required for bone formation, remodeling, and muscle contraction. In addition, calcium is required for fibrin synthesis, which is important for blood clotting. Calcium and phosphorus together account for over half of all minerals in the body. In addition to being required for bone formation, phosphorus is needed for normal metabolism, and it is an essential component of many enzyme systems.

Severe malnutrition increases the length of a patient’s hospital stay and the risk of infections, sepsis, and even death. Clinicians should routinely perform nutritional screening.

The author has performed a study to find out which of the essential factors are commonly lacking in diabetic foot ulcer patients. One hundred diabetic foot patients who had nonhealing ulcers with duration of more than 6 weeks were involved in the study. Serum levels of essential nutrients including protein, albumin, vitamin A, C, E, iron, magnesium, zinc, copper, and hemoglobin were checked after 8 h of fasting. Seventy-six percent and 61 % of the patients had serum protein and albumin levels in normal ranges, respectively. Among vitamins, only the level of vitamin C was low in 55 % of the patients. The levels of vitamin A and E were normal in 93 and 100 % of the patients. With regard to minerals, the levels of iron and zinc were low in 63 and 60 % of the patients, but the levels of magnesium and copper were usually normal. These results indicate that the serum levels of Hb, vitamin C, iron, and zinc are commonly low in diabetic foot ulcer patients.

More recently, the therapeutic effects of ultrasound energy in the KHz range have been examined. It has been proposed that low-frequency ultrasound in this range may improve wound healing via the production, vibration, and movement of micron-sized bubbles in the coupling medium and tissue. Several high-intensity ultrasound devices with contact probes are currently available for wound debridement. Generally used frequency and power for the debridement are 40 KHz and 50 W, respectively.

Ultrasonic debridement has been designed to optimize the well-known capabilities of high-intensity, low-frequency ultrasound to disrupt, inactivate, and remove bacterial organisms from surfaces and stimulate the body’s self-healing ability. When solution flows through the titanium alloy probe, attached to the handpiece distal end, the ultrasound scatters become mist, amplifies the mechanical vibration, and transfers the acoustic energy into the tissue via direct contact. Mechanical and hydrodynamic effects and the resulting cavitation produce tissue disruption, excision, fragmentation, and emulsion in the wound bed. The design of the individual wound care probes allows them to effectively debride a variety of wound shapes and a variety of tissue types, providing maximum wound debridement efficiency. The combination of probe shape and amplitude settings offers the surgeon a variety of options to match specific debridement requirements, from the removal of slough or fibrin to a full excisional debridement. The device is easy to use and suitable for a variety of solutions. Additionally, ultrasonic debridement can decrease healing time and reduce bleeding. Clinical applications include diabetic foot ulcers, venous ulcers, pressure sores, and burns.

HBO helps increase tissue oxygenation by administration of 100 % oxygen to patients within an airtight vessel under increased atmospheric pressure (Fig. 6.​33). Therefore, HBO can help cell activities for wound healing by increasing oxygen delivery to the key cells. However, there is controversy as to the effectiveness of HBO at this time.

Many authors have reported that increasing tissue oxygenation by administering supplemental hyperbaric oxygen can have a significant beneficial impact on wound healing, and some included fairly extensive cases. Ladurner et al. evaluated whether measuring TcPO₂ could be used to predict the risk of nonhealing and amputation in patients with diabetic foot ulcers. That study of 141 patients concluded that assessing TcPO₂ is suitable as a clinical screening tool for estimating the risk of nonhealing in patients with diabetic foot ulcers. Kranke et al. assessed the benefits of adjunctive HBO for treating chronic ulcers of the lower limbs using Cochrane methodology (literature-based meta-analysis) and extracted data from nine randomized controlled trials (total of 471 participants). Among them, eight trials (total of 455 participants) enrolled patients with diabetic foot ulcers. Their conclusion was that HBO therapy significantly improved healing of diabetic foot ulcers at 6 weeks of follow-up. In addition, consensus statements from an expert panel were that TcPO₂ <40 mmHg reduces the likelihood of amputation healing and that TcPO₂ >40 mmHg is usually associated with subsequent healing.

Although the effect of HBO therapy has been observed in various experimental and clinical studies, the use of HBO therapy is limited for several reasons. Clinical applications of HBO therapy are limited by high-cost, low availability of HBO chambers, need for trained personnel to monitor patients, poor patient compliance because of headache and otalgia, and the possibility of high oxidative potential contributing to pulmonary edema and brain injury. The occurrence of oxygen-toxic seizures after HBO therapy has also been reported. Cardiopulmonary, nephrologic, and neurologic comorbidities may be more frequent in patients with chronic wounds, who commonly have a poor general health condition. In addition, many patients with chronic wounds have difficulty moving to an HBO chamber or may have claustrophobia. For these reasons, the use of HBO therapy has been limited in patients with chronic wounds.