The Physiology of Wound Healing

Drawn from “Wound Management to 2026”. Details
See also, “Factors Affecting Wound Healing.”

When body tissue is damaged by trauma, surgery, hypoxia, or other destructive processes, the body’s physiology of wound healing quickly reacts to protect itself and begin the process of healing. Clean surgical wounds closed by primary intention heal rapidly and do not usually require additional medical intervention and support. Chronic wounds and those left to heal by secondary intention will require more attention from the medical team. Most of the literature describing the phases of wound healing has been written following investigation of clean, acute wounds, and the sequence and timing of the events described thus only relate to acute wounds. It is assumed that the chronic wound follows a similar wound-healing course with the timing of events delayed or prolonged compared with acute wounds.

All wounds must pass through three recognized physiological processes in order to achieve healing: the inflammatory phase, proliferative phase, and maturation phase. It is useful to view the stages of wound healing as distinct events, but in reality, there is overlap between the phases, and an individual wound may be in several phases at the same time. Unlike acute or surgical wounds, which heal by “primary intent” – the joining of the wound edges by sutures, staples, or adhesive strips – skin ulcers and severe burns heal by “secondary intent,” through the formation of granulation tissue, contraction of the wound, and epithelialization. A normal wound heals in about 21 days in organized phases of inflammation, proliferation, and remodeling, but chronic wounds often stall between the inflammatory and proliferation stages, creating wounds that can last for months or even years. It is only when all the stages have been accomplished over the entire wound surface that complete wound healing has been achieved.

Wound healing physiology is also alternatively divided into defensive, proliferative, and maturation; each phase must be allowed to occur without impediment for healing to be complete. The defensive phase occurs from the time of injury to three days and is characterized by hemostasis and inflammation. The clotting cascade is initiated, and white blood cells mobilize to defend and protect the area from bacterial invasion. Vasodilatation and serous exudate facilitate the removal of debris and the delivery of nutrients to injured tissue.

Proliferation lasts from day two until the area is healed and features granulation, contraction, and epithelialization. Granulation includes neo angiogenesis and collagen formation. Granular tissue is pale pink to beefy red, glistening, and has a rough surface due to blood vessels and collagen deposits. Contraction occurs as a result of myofibroblasts pulling collagen toward the cell body, and epithelialization is the migration of epithelial cells to resurface the area.

Maturation is the last phase of healing, and involves scar remodeling after wound closure. This phase may take years. Maturation sees a scar change from red to purple/pink to white, and from bumpy to flat.

Wound management priorities include: 1) reducing or eliminating causative factors (pressure, shear, friction, moisture, circulatory impairment, and/or neuropathy), 2) providing systemic support for healing (blood, oxygen, fluid, nutrition, and/or antibiotics), and, 3) applying the appropriate topical therapy (remove necrotic tissue or foreign body, eliminate infection, obliterate dead space, absorb exudate, maintain moist environment, protect from trauma and bacterial invasion, and provide thermal insulation).

wound market segments globally
Wound treatments are myriad.

The diversity of wounds and wound care products complicates the dressing selection process; many wounds have several options for dressings that are effective. Matching wound characteristics with dressing features is one important goal in the wound care and healing process. For example, a heavily exuding wound needs an absorptive dressing, and a wound with necrotic eschar needs a dressing that facilitates debridement. Dressings fall into several categories: gauze, hydrogel, hydrocolloid, transparent film, alginate, foam, and accessory products such as enzymes, growth factors, biological dressings, compression devices, support surfaces, and methods for securing dressings.

Factors affecting healing include tissue perfusion and oxygenation, presence or absence of infection, nutrition, medications, underlying disease, mobility and sensation, and age. Circulation and adequate oxygen saturation deliver nutrients for wound healing and gas exchange. All wounds disrupting the integument are contaminated, but not necessarily infected. Bacteria compete with tissues for nutrients, prolonging the inflammatory stage and delay collagen synthesis and epithelialization. Vitamin C, the B vitamins, zinc, and copper are necessary for collagen synthesis. Vitamin A combats the effects of steroids and protein is needed for collagen and skin growth. Steroids and immunosuppressive drugs suppress the inflammatory phase thus slowing the entire healing process. Underlying chronic disease(s) also competes for nutrients, increases risk of infection, and stresses the healing process. Limited mobility and/or sensation contribute to wound formation and impair the perception of wound presence or complications.

Debridement is necessary when necrotic eschar or fibrinous slough is present in the wound base. Necrotic eschar is thick, leathery, devitalized, black tissue, and slough is white or yellow tenuous tissue. Methods of debridement are described as sharp (surgical), mechanical (dressings), autolytic (dressings) and enzymatic (enzymes). Sharp debridement is indicated for extensive necrosis or for large wounds. Mechanical and autolytic debridement is indicated for many pediatric wounds and is accomplished with dressings. Mechanical debridement is done with a wet to dry dressing using woven gauze; as wet fibers dry, tissue adheres to the fiber and is removed when the dressing is removed. Autolytic debridement is also indicated for many pediatric wounds and is done with an occlusive dressing that retains moisture on the wound and allows white blood cells and enzymes to break down necrotic tissue. Hydrocolloids, transparent films, and hydrogels are effective for autolytic debridement. Enzymatic debridement is indicated when selective debridement is desired because enzymes only work on necrotic tissue. Enzymatic preparations contain fibrinolysin, collagenase, papain or trypsin in a cream or ointment base. Enzymatic debridement is slow, but effective, and instructions for using enzymes must be followed closely.

Wound cleansing removes dressing residue, microbes, and cellular debris (may include healing tissue). Cleansing products need to be safe for healing tissue and effective at removing debris. The adage “don’t put anything in a wound you wouldn’t put in your eye” are safe words to work by. Many topical cleansing agents and antiseptics are cytotoxic, and it is imperative to weigh the risks of cytotoxicity against the benefits of cleansing effectiveness and antimicrobial activity.

Normal saline is safe, effective, readily available, and inexpensive. Wound irrigation pressure needs to be high enough to remove debris and low enough to avoid traumatizing tissue. Pressures ranging from 4-15 pounds per square inch (psi) are effective for cleaning. For example, a 60cc catheter tip syringe delivers 4.2 psi, a 35cc syringe with a 19-gauge needle delivers 8.0 psi, and a Water Pik at its highest setting delivers >50 psi. Frequency of wound cleansing varies with wound characteristics and dressing selection, but once a day cleansing is a minimum. Clean versus sterile technique for dressing changes is constantly debated with varying outcomes and supporting arguments. Most importantly, consider the host system defenses and type of wound when deciding whether to use a clean or sterile technique for dressing changes and cleansing.

Wound assessment involves many parameters, but the following indices should be included in continued documentation of wound healing: size (length, width, depth), extent of tissue involvement (partial or full thickness; stage of pressure ulcer), presence of undermining or tracts, anatomic location, type of tissue in base (viable or nonviable), color (red, yellow, black categories), exudate, edges, presence of foreign bodies, condition of surrounding skin, and duration. Photography is useful for documenting progress and should include a measuring scale and date.


Drawn from MedMarket Diligence report #S254,  “Wound Management to 2026”. Details.

Global Wound Prevalence Forecast by Type, 2016-2026

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.

Source: MedMarket Diligence, LLC; Report #S254(Request excerpts.)

 

USA slipping behind Asia/Pacific markets in wound care sales

We present data from our 2016 to 2026 forecast of the global market for wound management products (report #S254, published March 2018). 


At a glimpse, you can see the overall trend in global wound management, including the relative size of each market. (The four regional sales charts are shown on the same scale to illustrate this.)  Most notably, the USA dominance of this global market is fading, as aggregate Asia/Pacific sales of all wound products will eclipse USA sales within the forecast period.

 

 

 

 

 

 


Source: MedMarket Diligence, LLC; Report #S254.

Looking at just the aggregate of all wound product types, Asia/Pacific relative sales are squeezing out shares in every other region.Source: MedMarket Diligence, LLC; Report #S254.

When we then look specifically at the USA versus Asia/Pacific, it illustrates that by 2020, Asia/Pacific’s sales of wound management products will eclipse those of the U.S., making it the largest regional wound management market.

Source: MedMarket Diligence, LLC; Report #S254.

Growth of wound care product sales worldwide

Wound care product sales are growing at wildly variable rates around the world, with extremes spanning from the emergence of new technologies in rapidly growing economies to the technologies with low innovation in sluggish economies.

MedMarket Diligence’s global analysis of wound care products, technologies, companies and markets reveals the full spectrum of growth rates for well established to rapidly emerging products.

Below is illustrated the high growth country/product segments in wound management, reflecting the rapid adoption of new technologies such as growth factors and bioengineered skin, as well as older products such as alginates that are gaining sales in rapidly developing economies.

wound-country-high

Source: MedMarket Diligence, LLC; Report #S249, “Wound Management, Worldwide Market and Forecast to 2021: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World.”

At the other end of the extreme are those very well established products growing at less than anemic rates in countries where the economy is not as robust and/or where the growth has been superseded by sales of more novel products. Conventional dressings and bandages offer considerably less demand than do growth factors, bioengineered skin and skin substitutes and similar new products.

wound-country-low

Source: MedMarket Diligence, LLC; Report #S249

Of course, growth of sales in wound management products (and any product) is defined as the percentage change in sales volume over time. Smaller markets (typically soon after they have formed as a result of their initial commercialization) tend to grow on a percentage basis much faster. Indeed, a $1 dollar sale in year 1 followed by a $2 sale in year 2 represents a 100% growth rate, while a $1 increase in sales from year 1 to year 2 for a $100 million market represents virtually zero growth. Conversely, a 1% increase in a $1.75 billion market is a $17.5 million increase. This is indeed obvious, but must be kept in mind when considering the growth rates discussed above.

Prevalence of dermal applications for sealants and glues

Skin securement has always been an essential final step in surgical procedures. In early years, the skin surface was sutured; in recent years a number of advances have been made, including new tapes, sutures, staples, hemostats, and glues.

Burns

Approximately 24,000 burn victims in the United States received skin grafts every year. These represent the very worst burn cases; in fact, approximately 25% of this group will die from their injuries. Glues and sutures are used to secure skin grafts in place and hemostats are used to prevent bleeding and to prepare the new skin for repair. Skin grafts provide an immediate covering for the patient that prevents further cell death, stimulates repair, and reduces fluid loss through the burnt skin. Products in this category may also be required to treat the skin after donor site material is taken from an intact region on the patient’s skin for skin grafting. Advances in sealant, hemostat, and closure technologies offer the potential to accelerate repair by creating the right environment to accelerate the healing process and provide better repair.

Pressure Ulcers

About 1.5 million pressure ulcer patients were treated in the United States in 2008. These wounds develop in immobile patients who often suffer from underlying biochemical deficiencies that lead to inadequate skin healing. Prevalence is highest in the old and infirm, and incidence is increasing in line with aging of the population. Sealants, hemostats, and closure products provide opportunities for a radical surgical method to treat these life-threatening wounds, which normally would be treated with conservative (though often sophisticated) wound healing products designed to reduce points of pressure, mask smell and absorb excess moisture while the body repairs itself. The strongest opportunity for use of surgically oriented products for repair of pressure ulcers is among young paraplegics and short-term acute care patients who are immobilized but otherwise healthy (approximately 5% of all pressure ulcers).

Diabetic Ulcers

Diabetes causes many abnormalities in tissue biochemistry and nutrition, many of which lead to impaired tissue healing. In addition, diabetes leads to conditions of hypoxia and peripheral neuropathy that can directly cause ulcers. Approximately 800,000 diabetics in the United States have diabetic foot ulcers; closure and securement products offer a surgical route to aiding repair that may offer potential to accelerate repair in a number cases.

Venous Ulcers

There are approximately one million venous ulcer patients in the United States today. Prevalence is increasing in line with aging demographics exacerbated by a sedentary lifestyle. Venous ulcers are caused by underlying vascular and venous flow abnormalities, which can often be treated by knowledgeable application of pressure bandaging and, in some cases, appropriate topical wound care. However, this treatment is largely symptomatic and many physicians believe surgical intervention to repair the underlying vascular abnormalities is required to effect a cure and avoid tissue breakdown. Sealants, hemostats, and closure products offer a surgical route to aiding repair that may offer potential to accelerate repair in a number cases.

Plastic Surgery

About 2 million cosmetic augmentation procedures are performed in the United States every year. The most popular procedures are liposuction (455,000) and breast augmentation (365,000). Most of the latter use synthetic materials and biomaterials for augmentation purposes. Other procedures where sealant products may be relevant include rhinoplasty (200,000), abdominoplasty (170,000) and eyelid surgery (230,000).

Adjunctive products for securement and closure offer potential to improve surgical procedure, reduce infections, and improve aesthetic and physiological properties of newly repaired tissues, as well as offering more rapid rehabilitation and the avoidance of donor site morbidity in approximately 27,000 of these operations involving the use of donated tissue from another region of the patient’s body.

 

dermal applications of sealants

Source: MedMarket Diligence, LLC; Report #S175, "Worldwide Surgical Sealants, Glues and Wound Closure, 2009-2013."

 

Wound Management: Wound Prevalance, Treatment Trends

From Report #S245, “Wound Management, 2007-2016: Established and Emerging Products, Technologies and Markets in the U.S., Europe, Japan and Rest of World,” published by MedMarket Diligence, LLC (November 2007).

Wound types fall into four general categories — surgical, traumatic, burns, and chronic — yet there is a wide variety of specific types, with different prevalence and growing at different rates. The exhibit below illustrates the current patient population (prevalence) and the compound annual growth rate for each wound type over the 2005-2014 period.

Wound Prevalence by Etiology Worldwide

Wound Management Trends

Surgical Wounds

Surgical wounds account for the vast majority of skin injuries. We estimate that there are over 100 million surgical incisions a year, which require some wound management treatment. Approximately 80% of these wounds use some form of closure product (sutures, staples, and tapes). Many employ hemostasis products, and use fabric bandages and surgical dressings.

Surgical wounds are projected to increase in number at an annual rate of 3.1%, but overall the severity and size of surgical wounds will continue to decrease over the next ten years as a result of the continuing trend toward minimally invasive surgery.

Surgical procedures generate a preponderance of acute wounds with uneventful healing and a lower number of chronic wounds, such as those generated by wound dehiscence or post-operative infection. Surgical wounds are most often closed by primary intention, using products such as sutures, staples, or glues, where the two sides across the incision line are brought close and mechanically held together. Surgical wounds that involve substantial tissue loss or may be infected are allowed to heal by secondary intention where the wound is left open under dressings and allowed to fill by granulation and close by epithelialization. Some surgical wounds may be closed through delayed primary intention where they are left open until such time as it is felt it is safe to suture or glue the wound closed.

A significant feature of all wounds is the likelihood of pathological infection occurring. Surgical wounds are no exception, and average levels of infection of surgical wounds are 7 to 10 percent dependent on the procedure. These infections can be prevented by appropriate cleanliness, surgical discipline and skill, wound care therapy, and antibiotic prophylaxis. Infections usually lead to more extensive wound care time, the use of more expensive products and drugs, significantly increased therapist time, and increased morbidity and rehabilitation time. A large number of wounds will also be sutured to accelerate closure, and a proportion of these will undergo dehiscence and require aftercare for healing to occur.

Traumatic Wounds

There are estimated to be 1.5 million cases of traumatic wounding every year. These wounds required cleansing and treatment with low adherent dressings to cover them, prevent infection, and allow healing by primary intention. Lacerations are a specific type of trauma wound that are generally more minor in nature and require cleansing and dressing for a shorter period of healing. Lacerations occur frequently (approximately 19 million cases a year) as a result of cuts and grazes and can usually be treated within the doctor’s surgery and outpatient medical center and hospital accident and emergency department.

Burns

Burn wounds can be divided into minor burns, medically treated, and hospitalized cases. Out-patient burn wounds are often treated at home, at the doctor’s surgery, or at outpatient clinics. As a result a large number of these wounds never enter the formal health service system. We estimate that approximately 3.3 million burns in this category do enter the outpatient health service system and receive some level of medical attention. These burns use hydrogels and advanced wound care products, and may even be treated with consumer based products for wound healing. Medically treated burn wounds usually get more informed care to remove heat from the tissue, maintain hydration, and prevent infection. Advanced wound care products are used on these wounds. Approximately 6.3 million burns like this are treated medically every year. Hospitalized burn wounds are rarer and require more advanced and expensive care. These victims require significant care, nutrition, debridement, tissue grafting and often tissue engineering where available. They also require significant aftercare and rehabilitation to mobilize new tissue, and physiotherapy to address changes in physiology.

Chronic Wounds

Chronic wounds generally take longer to heal and care is enormously variable, as is the time to healing. There are approximately 7.4 million pressure ulcers in the world that require treatment every year. Many chronic wounds around the world are treated sub-optimally with general wound care products designed to cover and absorb some exudate. The optimal treatment for these wounds is to receive advanced wound management products and appropriate care to address the underlying defect that has caused the chronic wound; in the case of pressure ulcers the causal effect is pressure and a number of advanced devices exist to reduce pressure for patients. There are approximately 11 million venous ulcers, and 11.3 million diabetic ulcers in the world requiring treatment. Chronic wounds are growing in incidence due to the growing age of the population, and due mostly to awareness and improved diagnosis. At present these factors are contributing to growth of this pool of patients faster than the new technologies are reducing the incidence of wounds by healing them.

Wound management products are also used for a number of other conditions including amputations, carcinomas, melanomas, and other complicated skin cancers, which are all on the increase.


See wound report #S245 description, table of contents here. This report may be ordered for immediate download online or may be purchased via Google Checkout, below.