The Physiology of Wound Healing

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

anatomy of human skin
Anatomy of human skin

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
Source: Medscape (

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 care market segmentation best done one country at a time

This month, MedMarket Diligence is publishing its biennial report on the global wound care market, “Worldwide Wound Management, Forecast to 2026: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World.Details.

Markets for medical technologies work according to the forces in play where products sell. There is no “global market”, per se, but an amalgamation of far-flung markets where, in one country, a new technology is embraced, and in another it’s passe or taboo or too expensive or de rigueur.

Cultural differences regarding medicine can be significant. How the sick are treated socially, how wounds are considered, the value of an innovation — may all be viewed differently through local lenses.

Differences in effective sales and distribution can exist, particularly for new technologies, in technology-importing countries.

Regulatory differences can be HUGE.  Besides the timing of FDA PMA or 510(K) versus the CE mark for the same technology, the regulatory entities are not entirely in sync regarding approval for new technologies.

On the global playing field, all active players know that some countries sre better than others at allowing foreign conpetition.

Even well established products, like traditional wound products (gauze, adherent, non-adherent), remain less well established in emerging markets.

below are the shares of each country’s total wound market represented by each technology, for non-adherent dressings, adherent dressings, gauze dressings, NPWT, and antimicrobial wound products.

The  net effect on local markets?

— Each country has greater/lesser demand for different technologies


Technology/Treatment Share of Country Total Wound Market

[For example, non-adherent wound dressings represent a little over 6% of the U.S. market, but as much as 16% of the market in China, and under 4% of the aggregate wound market in the rest of Asia/Pacific (Australia, India, etc.).]

non-adherent dressings

Source: MedMarket Diligence, LLC; Report S254.

Other traditional products like adherent dressings and gauze show a pattern of lesser use in the U.S., western European countries, and Japan.

traditional adherent dressings in wound care
Source: MedMarket Diligence, LLC; Report S254.

Traditional gauze is a less significant component of the U.S. or Japan, both of which have rapidly adopted and instead use more advanced technologies.

traditional gauze dressings in wound care
Source: MedMarket Diligence, LLC; Report S254

Negative Pressure Wound Therapy, a more involved wound care technology, shows different patterns in demand across countries than other wound products.

negative pressure wound therapy wound care
Source: MedMarket Diligence, LLC; Report S254.

The actual level of risk of infection, the perceived risk of infection, and the resulting differences in adoption of antimicrobials give rise to some different adoption than one might expect.

antimicrobial wound care products
Source: MedMarket Diligence, LLC; Report S254.

Markets for advanced wound care technologies, such bioengineered skin or growth factors (not shown), illustrates a common dynamic, with the highest country use being the U.S. and whose manufacturers have often pursued the U.S. market for new technology introduction, to be followed by Europe, Asia, South America, etc. as technology migrates to less well developed markets.

Other products in wound with their own country-to-country dynamics include film dressings, foam, hydrogel, hydrocolloid, alginate, collagen, and growth factors.

See Report #S254, publishing March 2018.


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.)


Factors Affecting Wound Healing… (more)

In addition to the factors we detailed in a past post, we show here a number of frameworks used by clinicians to properly assess the condition of wounds and the wound healing process, providing a systematic way to optimize wound healing.


“DIMES” focuses on providing an efficient use of resources in the management of chronic wounds.

The DIMES Acronym for Treatment Planning and Products

Source: MedMarket Diligence, LLC Report S254; GS Schultz, et al. Wound bed preparation: a systematic approach to wound management. Wound Repair Regen. 2003 Mar;11 Suppl 1:S1-28.)


“TIME” is focused specifically on wound bed preparation, a key determinant of wound healing.

TIME Acronym for Wound Bed Preparation

Source: MedMarket Diligence, LLC Report S254; GS Schultz, et al. Wound bed preparation: a systematic approach to wound management. Wound Repair Regen. 2003 Mar;11 Suppl 1:S1-28.)


“DIDNT HEAL” is similarly intended to be a useful mnemonic regarding key wound healing factors.

Source: MedMarket Diligence, LLC Report S254.

March 2018: Worldwide Wound Management, Forecast to 2026″. Report #S254.

Bioengineered Skin and Skin Substitutes, Sales and Growth, 2017 to 2026

The use of bioengineered skin and skin substitutes in the treatment of wounds is on a strong, but variable growth curve. Currently, the highest sales of these products in wound management occurs in the United States, where sales are in excess of $700 million annually already and growth in sales of these products is projected at or near 10% annually through 2026.

While China “only” has sales of just over $200 million in bioengineered skin and skin substitutes, the projected >20% CAGR to 2026 will result in China’s sales approximating U.S. sales in a decade.

Source: MedMarket Diligence, LLC; Report #S254.

Wound Care Market Shares Worldwide

Analyzing data from Report #S254 ,”Wound Management to 2026″, we present the distribution of top competitor’s sales in each segment in 2017. Smith & Nephew, Johnson & Johnson, and 3M dominate the global wound management, with varying dominance between them — or by other companies — in each segment.

Source: MedMarket Diligence, LLC; Report #s254. (Publishing March 2018)

S&N leads the global market, following closely by JNJ. Both companies are active in multiple segments of wound management. S&N has lower traditional wound management product sales (simple dressings and bandages) and higher sales of “advanced” wound management products. J&J does $800 million more sales in traditional dressings, gauze and bandages than S&N, but lesser involvement in newer wound technologies such as NPWT, bioengineered skin, and growth factors.

Source: MedMarket Diligence, LLC; Report #s254. (Publishing March 2018)


China, USA, and Japan Wound Markets

The distribution of sales of different wound management products naturally varies from one country to the next based on pricing, reimbursement, local clinical practice trends, cultural characteristics, and any number of other drivers. The net effect is different distributions.

The goal for wound market players in gauging opportunities is knowing where things are going.

In the global aggregate, here is how we anticipate the market for wound management products in 2016 will stack up compared to 2026:

Source: MedMarket Diligence, LLC; Report #S254.

As you can see, traditional wound management products are giving way in the balance to advanced products. How this global dynamic plays out differently in local markets is important for manufacturers to consider, as shown in the comparison of wound markets in China, the USA and Japan, both in 2017 and 2026.

Source: MedMarket Diligence, LLC; Report #S254.

You can see (in graph, above) the difference in relative sizes of the USA, Japan and China wound markets, in both 2017 and 2026. The largest relative increase in the absolute market will occur in China as a result of its double-digit growth rate. By comparison, the USA market overall is growing slightly faster than Japan (5.8% versus 4.2%, CAGR 2017-26).

Source: MedMarket Diligence, LLC; Report #S254.

More remarkable is the difference in distribution of products sold in these three countries. With the exception of a consistent general decline in relative sales of traditional products, each of these countries is exhibiting different rates of change in the distribution of wound product sales from 2017 to 2026.

March 2018
Worldwide Wound Management, Forecast to 2026:

Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World.” Report #S254.


Wound Care Shares: Traditional/Advanced Products, Fragmented/Dominated

Traditional wound care products (gauze, non-adherents, and adhesive dressings) encompass low innovation, commodity-like pricing and ultimately different sets of competitors than advanced wound care products.

Below illustrates the global market shares of wound care sales in traditional versus advanced  products. JNJ and S&N have swapped positions in the traditional versus advanced wound markets.

Source: Report #S254; MedMarket Diligence.


Among wound care’s most fragmented markets in terms of competitive activity are hydrocolloids and foam dressings, with no one competitor dominating the market. While 3M and S&N control significant shares of the hydrocolloid and foam dressings market, their aggregate share is still well under 50%.

Global Wound Management Market Shares in
Hydrocolloids and Foam Dressings, 2017

Source: Report #S254; MedMarket Diligence.

By comparison, other markets have clearly dominant players, such as in negative pressure wound therapy (NPWT) and growth factors used in wound care. In each, there is clearly one dominant player and the top two players control a large majority of each market.

Global Wound Management Market Shares in
Hydrocolloids and Foam Dressings, 2017

Source: Report #S254; MedMarket Diligence.



Country and Regional Variability in Growth of Wound Management Sales

As illustrated in a previous post, wound management products are a spectrum from the simple to the complex:

Source: MedMarket Diligence Report #S254.

Generally, the longer the product has been around (e.g., gauze), the less complex it is compared to emerging technologies…

…BUT simpler is easy to adopt and, with well established sales, growth on a percentage basis will be low (see area in red).

Generally, new technologies incorporate rarer materials, have more complex construction, and may cost considerably more…

…BUT complex technologies may be far more effective clinically than older technologies and may allow treatment where no older technology could, and with low initial sales (penetrated potential), growth on a percentage bases will be high (see area in green).

Country and Regional Variation in Growth Rates

While this size-to-growth dynamic exists for most product types, the dynamic varies from one geographic region to the next. The time point at which a particular product/technology starts to be more rapidly adopted — or the rate at which use of  established products are use starts to decline — can vary considerably from country to country.

As a result, there will be variability in sales growth rates for a product in one country/region versus another.

For example, the 2017 to 2026 compound annual growth rate in sales of Alginates in wound management range from a low of 5.3% in one country to a high of 24.3% in another country. (If you make alginates, in which country would YOU like to compete?)

Regionally, as in USA versus Europe versus Asia/Pacific, etc., there is less variation in growth rates for any given product in that region. For alginates:

country-to-country variation in CAGR: 19%
region-to-region variation in CAGR: 7.8%

In other words, the difference between the countries with the highest and lowest CAGRs for alginate sales is 19%, while the difference between regions shows one region with a 7.8% higher CAGR for alginates than the lowest growth region.

Source: MedMarket Diligence, LLC; Report #S254.

Before chasing after that high growth rate, it is important to know the underlying volume. (Sales of $1 in year 1 and $2 in year 2 is a 100% growth rate, but it’s absolute growth of only $1.)

See the full REPORT, “Wound Management to 2026” details or order online. Please also see the forecast and market share data available separately from the report.


Highest growth in wound management sales to 2026 by product, region

Whenever we complete a new analysis of the global wound management market, as we have just done, we like to present top line findings, such as the top “region-wound segment” growth markets.

We assess the 10-year sales size and growth for 13 different wound product segments worldwide, in major geographic regions and individual countries — USA, Rest of N. America, Latin America, Europe, United Kingdom, Spain, France, Germany, Italy, Rest of Europe, Asia/Pacific, Japan, Korea, China, Rest of Asia/Pacific, Rest of World.

Below we show the top 15 combinations of regional market and product segments in descending order of their compound annual growth rate from 2017 to 2026.

Source: MedMarket Diligence, LLC; Report #S254.

As becomes clear, the greatest relative growth in sales in the area of wound management is in several wound care product types — bioengineered skin & skin substitutes, growth factors — and the geographic regions of Japan, Rest of World, China, Germany, Asia-Pacific.  This reflects the high level of investment and attention in Asian markets, especially China.

[The complete set of wound market forecast data, from 2016 to 2026, is available at 2018 Wound Management Report #S254. The associated full report, including this data, will be publishing March 2018.]