Healthcare systems move billions in global wound care sales, yet chronic wounds still are a chronic problem. Despite the legion of products developed for wound care, from dressings to bioengineered skin, the obesity- and age-driven increase in chronic slow-healing and non-healing wounds plague healthcare systems globally. Results according to MedMarket Diligence’s biennial, 2018 Wound Management report (#S254).
BIDDEFORD, Maine – April 1, 2018 – PRLog — Research and routine clinical practice in wound management have advanced the science to better understand and address chronic wounds, but much work remains for research and manufacturing to impact the growing caseload.
Chronic wounds represent a large but still underestimated problem for health systems globally and industry needs to step up in response, according to MedMarket Diligence, LLC.
“Our recent research shows that chronic wounds, which have long been no secret to clinicians, epidemiologists, and product manufacturers as a growing health problem, are actually even more prevalent and costly than has been previously reported,” says Patrick Driscoll of MedMarket Diligence, who has tracked wounds in clinical practice and industry for 25 years.
Care of chronic wounds is a significant, global burden on healthcare systems. In the USA alone, it is estimated that at least 6.7 million people suffer with chronic wounds, requiring treatment in excess of $20-50 billion per year (estimates vary according to the definitions). A report from the UK suggests, based on National Health System (NHS) data, that chronic wound prevalence in developed countries is about 6% and that care of chronic wounds accounts for around 3-5.5% of total healthcare spending in those countries. (Phillips CJ, et al. Estimating the costs associated with the management of patients with chronic wounds using linked routine data. Int Wound J. 2015. doi: 10.1111/iwj.12443.)
Definitions help clinicians determine whether a wound is healing or not. For example, for venous leg ulcers (VLUs), if the wound has not shown at least a 40% reduction in wound size in about four weeks, then additional therapies are called for. A non-healing foot ulcer is generally defined to be any ulcer that is unresponsive to standard therapies and persists after four weeks of standard care. Once a foot ulcer occurs, unfortunately some 60% of patients end up moving into the chronic non-healing category. Many diabetics develop foot ulcers.
Chronic wounds and burns continue to present challenging clinical problems. For example, chronic wounds may present with persistent infections, inflammation, hypoxia, non-responsive cells at the wound edge, the need for regular debridement, etc. For DFUs, it is important for the patient to continuously wear an offloading device such as a special boot. Additionally, the practitioner must carefully debride not only the necrotic tissue in the wound bed, but the wound edges. Cells at the wound edge seem to be unresponsive to typical healing signals, and therefore must be removed to promote and support proper healing.
To the person with a chronic wound, the condition represents pain, social and psychological debilitation and usually a financial load. To society, wound care—and especially the treatment of difficult-to-heal wounds—may represent great human suffering, social discomfort, days lost from work, mental health problems, recurrent infections and great economic burden and the human burden of wound care. Having a chronic wound not only necessitates physical care of the wound, including cleaning, disinfecting, irrigating, and changing dressings; it also impacts the emotional and psychological health of the patient. Depression can set in due to a lower quality of life and dependence on others for care of the wound, as well as for overall assistance, both physical and financial. Wounds may cause odors or may have visible drainage, staining clothing and triggering feelings of embarrassment and shame. These in turn may lead to isolation due to decreased mobility and the fear of being a burden on family and friends. To make things worse, increased stress can slow the progress of wound healing. For all of these reasons, chronic wounds drive product development.
In caring for a chronic wound, the dressing costs are only part of the picture; the less visible costs include such items as nursing care, medications for pain and infections, and hospitalization. Hospitalization is a leading cost driver for wound care, accounting for at least 50% of the global economic burden. Nursing time to properly care for the patient with a chronic wound can be lengthy, and this is time that could be spent with other patients. In a new report published in the December 2017 online version of the International Society for Pharmacoeconomics and Outcomes Research’s (ISPOR) Value in Health journal (An Economic Evaluation of the Impact, Cost, and Medicare Policy Implications of Chronic Nonhealing Wounds. Nussbaum, Samuel R. et al. Value in Health, Volume 21 , Issue 1 , 27 – 32) (see the study), the researchers found that the costs related to wound care in the Medicare population (USA) were much higher than originally estimated, and that care took place primarily in outpatient settings. For the calendar year 2014, there is considerable variation in the estimates originating from different sources:
“Total Medicare spending estimates for all wound types ranged from $28.1 to $96.8 billion. Including infection costs, the most expensive estimates were for surgical wounds ($11.7, $13.1, and $38.3 billion), followed by diabetic foot ulcers ($6.2, $6.9, and $18.7 billion,). The highest cost estimates in regard to site of service were for hospital outpatients ($9.9–$35.8 billion), followed by hospital inpatients ($5.0–$24.3 billion).”
The development of advanced wound care dressings, devices and biologics is helping to change this situation. Although these advanced products may seem (or may be) expensive, they end up saving money for health care systems by healing wounds more rapidly.
The wound care industry remains quite fragmented, with about eight companies holding leading market shares, but with possibly thousands of small cap companies around the world that are also manufacturing and marketing various wound care products. The Traditional Wound Care space remains attractive, in part since gauze dressings are relatively easy to manufacture and are also still the most commonly-used wound dressing. Even a small company can invent a novel twist to a dressing and experience a rise in profits and inroads into the market.
Low to medium industry concentration. As the traditional and advanced market shares diagrams below demonstrate, there are five to eight major players in Traditional and Advanced Wound Care Markets.
While these firms account for about 79% and 73% of the total markets, respectively, a significant portion of these markets are covered by hundreds or thousands of Other companies. This low to medium level of concentration means that smaller companies, or large companies looking to break into Wound Care, are able to do so more easily than if, say, three companies controlled 95% of the market.
Johnson & Johnson is estimated to be the Traditional Wound Care market leader with about 26% share, followed by Smith & Nephew, 3M Health Care and Hartmann. Medline Industries is estimated to account for about 8%, while Others account for about 21% of this market.
Breaking into the Advanced Wound Care markets presents a somewhat greater challenge. Here, the leading companies have invested heavily in R&D to gain strategic competitive advantage, as well as to create improved products for patients. Smith & Nephew is holds an estimated 21% of this market, followed by Acelity and Johnson & Johnson with 11% each, and Mölnlycke, 3M Health Care, Hartmann, Cardinal Health and ConvaTec accounting for smaller shares. Here again, Others accounts for at least 27% of this market.
Opportunities exist in both Traditional and Advanced Wound Care, especially if a company is in the position of acquiring part or all of an existing wound care company, and if the company can then invest in the development of its new products. If points of distribution overlap, then so much the better.
Relatively low barriers to entry. Good news for companies wishing to break into wound care: barriers to entry into the traditional wound dressing segments (Adherents, Gauze and Non-Adherent Dressings) are relatively low, while demand remains strong. Typically, once a company is established in a traditional segment, it may either plow revenues into research and development, or it may acquire companies to more easily break into new product segments and markets. Many companies in wound care have followed just this path to gain market share and make an impact in the industry.
From, “Wound Management to 2026”; Report S254. Excerpts available.
The clinical driver of sales in wound care is the prevalence of different wound types and the associated cost to manage them. While surgical wounds made by primary intent as part of surgical procedures (e.g., excision of skin lesion, appendectomy, coronary artery bypass graft, etc.) represent the biggest source of wounds, the biggest focus on reining in costs in medtech is slow-healing, chronic wounds, such as ulcers.
We have projected the global prevalence for the most common wound types through 2026, shown below.
Excerpted from, “Worldwide Wound Management, Forecast to 2024: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”, Report #S251.
A delicate physiological balance must be maintained during the healing process to ensure timely repair or regeneration of damaged tissue. Wounds may fail to heal or have a greatly increased healing time when unfavorable conditions are allowed to persist. An optimal environment must be provided to support the essential biochemical and cellular activities required for efficient wound healing and to remove or protect the wound from factors that impede the healing process.
Factors affecting wound healing may be considered in one of two categories depending on their source. Extrinsic factors impinge on the patient from the external environment, whereas intrinsic factors directly affect the performance of bodily functions through the patient’s own physiology or condition.
Preparation of the wound bed (WBP) is essential for the support of efficient and effective healing, especially when advanced wound care products are to be used. WBP involves removing localized barriers to healing, such as exudate, dead tissue or infected tissue.
Wound Bed Preparation: the TIME and DIMES acronyms
WBP involves debridement, reduction and neutralization of the bioburden and management of exudate from the wound. The TIME acronym provides a systematic way to manage wounds by looking at each stage of wound healing. The goal is to have the best, thoroughly-vascularized wound bed possible.
TIME stands for:
T: Tissue, non-viable or deficient.
The wound care professional should look for non-viable tissue, which includes necrotic tissue, tissue which has sloughed off, or non-viable tendon or bone.
I: Infection or Inflammation
Examine the wound for infection, inflammation or other signs of infection. Are there clinical signs that there may be a problem with bacterial bioburden?
M: Moisture Balance
Is the wound too dry, or does it have excess exudate?
What is the objective of topical therapy: absorption or drainage?
E: Edge of wound—non-advancing or undermined
Examine the edges of the wound. Are the edges undermined, or is the epidermis failing to migrate across the granulation tissue?
The DIMES acronym is very similar to TIME:
For wounds with the ability to heal, adequate and repeated debridement is an important first step in removing necrotic tissue. Debridement may also help healing by removing both senescent cells that are no longer capable of normal cellular activities and biofilms that may be shielding bacterial colonies.
The level of bacterial damage may include contamination (organisms present), colonization (organisms present which may cause surface damage if critically colonized) or infection. Treatment needs to make a match between the individual patient’s wound and the appropriate product.
Clinicians need to create a careful balance in the wound such that the environment is neither too wet nor too dry. The environment itself will change as the wound heals.
The clinician should carefully examine and monitor the wound edge. If the wound edge is not migrating after appropriate wound bed preparation, and if healing appears to be stalled, then more advanced wound care therapies should be considered.
Supportive Products and Services
There are additional products which support wound healing yet don’t fall into one of these steps. For example, proper nutritional support is important to achieving the goal of a fully healed wound.
Other factors such as alcohol abuse, smoking, and radiation therapy
Mechanical stress factors include pressure, shear, and friction. Pressure can result from immobility, such as experienced by a bed- or chair-bound patient, or local pressures generated by a cast or poorly fitting shoe on a diabetic foot. When pressure is applied to an area for sufficient time and duration, blood flow to the area is compromised and healing cannot take place. Shear forces may occlude blood vessels, and disrupt or damage granulation tissue. Friction wears away newly formed epithelium or granulation tissue and may return the wound to the inflammatory phase.
Debris, such as necrotic tissue or foreign material, must be removed from the wound site in order to allow the wound to progress from the inflammatory stage to the proliferative stage of healing. Necrotic debris includes eschar and slough. The removal of necrotic tissue is called debridement and may be accomplished by mechanical, chemical, autolytic, or surgical means. Foreign material may include sutures, dressing residues, fibers shed by dressings, and foreign material which were introduced during the wounding process, such as dirt or glass.
Temperature controls the rate of chemical and enzymatic processes occurring within the wound and the metabolism of cells and tissue engaged in the repair process. Frequent dressing changes or wound cleansing with room temperature solutions may reduce wound temperature, often requiring several hours for recovery to physiological levels. Thus, wound dressings that promote a “cooling” effect, while they may help to decrease pain, may not support wound repair.
Desiccation and Maceration
Desiccation of the wound surface removes the physiological fluids that support wound healing activity. Dry wounds are more painful, itchy, and produce scab material in an attempt to reduce fluid loss. Cell proliferation, leukocyte activity, wound contraction, and revascularization are all reduced in a dry environment. Epithelialization is drastically slowed in the presence of scab tissue that forces epithelial cells to burrow rather than freely migrate over granulation tissue. Advanced wound dressings provide protection against desiccation.
Maceration resulting from prolonged exposure to moisture may occur from incontinence, sweat accumulation, or excess exudates. Maceration can lead to enlargement of the wound, increased susceptibility to mechanical forces, and infection. Advanced wound products are designed to remove sources of moisture, manage wound exudates, and protect skin at the edges of the wound from exposure to exudates, incontinence, or perspiration.
Infection at the wound site will ensure that the healing process remains in the inflammatory phase. Pathogenic microbes in the wound compete with macrophages and fibroblasts for limited resources and may cause further necrosis in the wound bed. Serious wound infection can lead to sepsis and death. While all ulcers are considered contaminated, the diagnosis of infection is made when the wound culture demonstrates bacterial counts in excess of 105 microorganisms per gram of tissue. The clinical signs of wound infection are erythema, heat, local swelling, and pain.
Chemical stress is often applied to the wound through the use of antiseptics and cleansing agents. Routine, prolonged use of iodine, peroxide, chlorhexidine, alcohol, and acetic acid has been shown to damage cells and tissue involved in wound repair. Their use is now primarily limited to those wounds and circumstances when infection risk is high. The use of such products is rapidly discontinued in favor of using less cytotoxic agents, such as saline and nonionic surfactants.
Medication may have significant effects on the phases of wound healing. Anti-inflammatory drugs such as steroids and non-steroidal anti-inflammatory drugs may reduce the inflammatory response necessary to prepare the wound bed for granulation. Chemotherapeutic agents affect the function of normal cells as well as their target tumor tissue; their effects include reduction in the inflammatory response, suppression of protein synthesis, and inhibition of cell reproduction. Immunosuppressive drugs reduce WBC counts, reducing inflammatory activities and increasing the risk of wound infection.
Other Extrinsic Factors
Other extrinsic factors that may affect wound healing include alcohol abuse, smoking, and radiation therapy. Alcohol abuse and smoking interfere with body’s defense system, and side effects from radiation treatments include specific disruptions to the immune system, including suppression of leukocyte production that increases the risk of infection in ulcers. Radiation for treatment of cancer causes secondary complications to the skin and underlying tissue. Early signs of radiation side effects include acute inflammation, exudation, and scabbing. Later signs, which may appear four to six months after radiation, include woody, fibrous, and edematous skin. Advanced radiated skin appearances can include avascular tissue and ulcerations in the circumscribed area of the original radiation. The radiated wound may not become evident until as long as 10-20 years after the end of therapy.
Intrinsic factors that directly affect the performance of healing are:
Chronic diseases, such as circulatory conditions, anemias and autoimmune diseases, influence the healing process as a result of their influence on a number of bodily functions. Illnesses that cause the most significant problems include diabetes, chronic obstructive pulmonary disease (COPD), arteriosclerosis, peripheral vascular disease (PVD), heart disease, and any conditions leading to hypotension, hypovolemia, edema, and anemia. While chronic diseases are more frequent in the elderly, wound healing will be delayed in any patient with a pre-existing underlying illness.
Chronic circulatory diseases which reduce blood flow, such as arterial or venous insufficiency, lower the amount of oxygen available for normal tissue activity and replacement. Anemias such as sickle-cell anemia result in reduced delivery of oxygen to tissues and decreased ability to support wound healing.
Normal immune function is required during the inflammatory phase by providing the WBCs (white blood cells) that orchestrate or coordinate the normal sequence of events in wound healing. Autoimmune diseases such as lupus and rheumatoid arthritis interfere with normal collagen deposition, and impair granulation.
Diabetes is associated with delayed cellular response to injury, compromised cellular function at the site of injury, defects in collagen synthesis, and reduced wound tensile strength after healing. Diabetes-related peripheral neuropathy (DPN), which reduces the ability to feel pressure or pain, contributes to a tendency to ignore pressure points and avoid pressure relief strategies.
Acquired Immune Deficiency Syndrome
Patients with acquired immunodeficiency syndrome (AIDS) have significant impact on the wound healing market as their numbers rise and their average life expectancy increases. Patients in the latter stages of the disease experience drastic reductions in mobility, activity, and nutritional status, placing them at high risk for the development of pressure ulcers. Minor scrapes or abrasions are at high risk for infection and may progress to full-thickness wounds requiring antibiotic therapy and aggressive wound management. Skin tumors, such as Kaposi’s sarcoma, lead to surgical incisions closed by secondary intention requiring the use of appropriate dressings.
The skin of AIDS patients becomes drier as the syndrome progresses. As the CD4+ T cell count falls below 400/mm3, pruritus increases and erythematous patches appear on the skin, progressing to ichthyosis and appearing as large polygonal scales, especially on the lower limbs. Histological changes include hyperkeratosis and thinning of the granular layer of the epidermis. As skin becomes more fragile, care must be exercised in the selection of tapes and adhesive dressings to avoid skin stripping and skin tears.
Observable changes in wound healing in the elderly include increased time to heal and the fragile structure of healed wounds. Delays are speculated to be the result of a general slowing of metabolism and structural changes in the skin of elderly people. Structural changes include a flattening of the dermal-epidermal junction that often leads to skin tears, reduced quality and quantity of collagen, reduced padding over bony prominences, and reduction in the intensity of the immune response.
Body build can affect the delivery and availability of oxygen and nutrients at the wound site. Underweight individuals may lack the necessary energy and protein reserves to provide sufficient raw materials for proliferative wound healing. Bony prominences lack padding and become readily susceptible to pressure due to the reduced blood supply of wounds associated with bony prominences. Poor nutritional habits and reduced mobility of overweight individuals lead to increased risk of wound dehiscence, hernia formation, and infection.
Healing wounds, especially full-thickness wounds, require an adequate supply of nutrients. Wounds require calories, fats, proteins, vitamins and minerals, and adequate fluid intake. Calories provide energy for all cellular activity, and when in short supply in the diet, the body will utilize stored fat and protein. The metabolism of these stored substances causes a reduction in weight and changes in pressure distribution through reduction of adipose and muscle padding. Sufficient dietary calories maintain padding and ensure that dietary protein and fats are available for use in wound healing. In addition, adequate levels of protein are necessary for repair and replacement of tissue. Increased protein intake is particularly important for wounds where there is significant tissue loss requiring the production of large amounts of connective tissue. Protein deficiencies have been associated with poor revascularization, decreased fibroblast proliferation, reduced collagen formation, and immune system deficiencies.
Reduced availability of vitamins, minerals, and trace elements will also affect wound healing. Vitamin C is required for collagen synthesis, fibroblast functions, and the immune response. Vitamin A aids macrophage mobility and epithelialization. Vitamin B complex is necessary for the formation of antibodies and WBCs, and Vitamin B or thiamine maintains metabolic pathways that generate energy required for cell reproduction and migration during granulation and epithelialization. Iron is required for the synthesis of hemoglobin, which carries oxygen to the tissues, and copper and zinc play a role in collagen synthesis and epithelialization.
Adequate nutrition is an often-overlooked requirement for normal wound healing. Inadequate protein-calorie nutrition, even after just a few days of starvation, can impair normal wound-healing mechanisms. For healthy adults, daily nutritional requirements are approximately 1.25-1.5 g of protein per kilogram of body weight and 30-35 calories/kg. These requirements should be increased for those with sizable wounds.
Malnutrition should be suspected in patients presenting with chronic illnesses, inadequate societal support, multisystem trauma, or GI or neurologic problems that may impair oral intake. Protein deficiency occurs in about 25% of all hospitalized patients.
Chronic malnutrition can be diagnosed by using anthropometric data to compare actual and ideal body weights and by observing low serum albumin levels. Serum prealbumin is sensitive for relatively acute malnutrition because its half-life is 2-3 days (vs 21 d for albumin). A serum prealbumin level of less than 7 g/dL suggests severe protein-calorie malnutrition.
Vitamin and mineral deficiencies also require correction. Vitamin A deficiency reduces fibronectin on the wound surface, reducing cell chemotaxis, adhesion, and tissue repair. Vitamin C is required for the hydroxylation of proline and subsequent collagen synthesis.
Vitamin E, a fat-soluble antioxidant, accumulates in cell membranes, where it protects polyunsaturated fatty acids from oxidation by free radicals, stabilizes lysosomes, and inhibits collagen synthesis. Vitamin E inhibits prostaglandin synthesis by interfering with phospholipase-A2 activity and is therefore anti-inflammatory. Vitamin E supplementation may decrease scar formation.
Zinc is a component of approximately 200 enzymes in the human body, including DNA polymerase, which is required for cell proliferation, and superoxide dismutase, which scavenges superoxide radicals produced by leukocytes during debridement.
From, “Worldwide Wound Management, Forecast to 2024: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”. Report #S251. Available online.