Traditional and Advanced Wound Product Types

Wound management technologies have been under development for hundreds of years. The current state of product and technology development is now largely represented by thirteen different product categories described with their specific typical applications (1)Specific companies and products are detailed in “Wound Management to 2026”, report S254.

Wound Management Technologies By Type

Wound product categoryDescriptionPotential applicationsProduct and Manufacturer Examples
Traditional GauzeInexpensive, common, breathable, usually dries out the wound, may stick to wound causing damage when removedMay be used to secure a dressing in place, or directly over any wound type to keep it clean while allowing aeration.See link
Traditional AdherentDry, inexpensive, common, non-absorbent, will not stick to wound. Usually uses a wide mesh material with a finer mesh or foam, nonstick material.Applied directly to wound; used for large surface wounds such as abrasions or burns. Indicated when a good granulation bed has developed.

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Traditional Non-AdherentConforms to wound, keeps wound bed moist, will not stick to the surface of wound.Light to moderately exudative wounds, burns.

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FilmAvailable as adhesive, thin transparent polyurethane film, and as a dressing with a low adherent pad attached to the film.Clean, dry wounds, minimal exudate; also used to cover and secure underlying absorptive dressing, and on hard-to-bandage locations, such as heel.

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FoamPolyurethane foam dressing available in sheets or in cavity filling shapes. Some foam dressings have a semipermeable, waterproof layer as the outer layer of the dressingEnables a moist wound environment for healing. Used to clean granulating wounds with moderate to severe exudation.

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HydrogelColloids that consist of polymers that expand in water. Available in gels, sheets, hydrogel impregnated dressings.Provides moist wound environment to add moisture to dry wound, aids in cell migration, reduces pain, helps to rehydrate eschar. Used on dry, sloughy or necrotic wounds.

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HydrocolloidMade of hydroactive or hydrophilic particles attached to a hydrophobic polymer. The hydrophilic particles absorb moisture from the wound, convert it to a gel at the interface with the wound. Conforms to wound surface; waterproof and bacteria proof.Gel formation at wound interface provides moist wound environment. Dry necrotic wounds, or for wounds with minimal exudate. Also used for granulating wounds.

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AlginateA natural polysaccharide derived from seaweed; available in a range of sizes, as well as in ribbons and ropes.Because highly absorbent, used for wounds with copious exudate. Can be used in rope form for packing exudative wound cavities or sinus tracts.

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AntimicrobialBoth silver and honey are used as antimicrobial elements in dressings.Silver: Requires wound to be moderately exudative to activate the silver, in order to be effective

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CollagenAvailable in several forms, including gels, pads, pastes, particles, sheets, solutions, and are derived from bovine, porcine or avian sources. Collagen dressings are often used for PUs, VLUs, skin donor sites and surgical wounds, arterial ulcers, DFUs, second-degree burns and trauma wounds.

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NPWTComputerized vacuum device applies continuous or intermittent negative or sub-atmospheric pressure to the wound surface. NPWT accelerates wound healing, reduces time to wound closure. Comes in both stationary and portable versions.May be used for traumatic acute wound, open amputations, open abdomen, etc. Seems to increase burn wound perfusion. Also used in management of DFUs. Contraindicated for arterial insufficiency ulcers. Contraindicated if necrotic tissue is present in over 30% of the wound.

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Bioengineered Skin & Skin SubstitutesBio-engineered skin and soft tissue substitutes may be derived from human tissue (autologous or allogeneic), xenographic, synthetic materials, or a composite of these materials.Burns, trauma wounds, DFUs, VLUs, pressure ulcers, postsurgical breast reconstruction, bullous diseases

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Growth FactorsOften derived from human placenta from a healthy delivery (i.e. amniotic tissue allografts) and amniotic fluid components.May be used for any type of wound, but most often used for chronic, non-healing wounds such as DFUs and VLUs, and potentially with second-degree burns.

"

Source: MedMarket Diligence, LLC; Report S254.

References   [ + ]

1. Specific companies and products are detailed in “Wound Management to 2026”, report S254

Billions in global wound care sales, yet chronic wounds still a chronic problem

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).


Trends in wound prevalence by type
Trends in wound prevalence by type including chronic wounds

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.

Wound management is the subject ongoing research and publications (https://mediligence.com/s254/) by MedMarket Diligence, LLC. https://mediligence.com.

Contact
Patrick Driscoll

The Human Burden of Wound Care

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.

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.

Industry Structure

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.

Traditional Wound Care Market Shares, 2017

Source: Report S254, “Wound Management to 2026”.

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.

Advanced Wound Care Market Shares, 2017

Source: Report S254. 

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 on request.

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 care market segmentation best done one country at a time

In March 2018, MedMarket Diligence published 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 relative demand for different technologies, without respect to overall market size.


Technology/Treatment Share of Country Total Wound Market

The balance of sales across different wound technologies varies by country, with different products accounting for greater or lesser shares of the total wound sales per country. Below are illustrated, for example, that non-adherent dressings account for a higher share of wound product sales in China than in all other countries.

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

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

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.

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, published March 2018.

 

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”, “TIME” and “DIDNT HEAL”

“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.

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
NPWT and Growth Factors, 2017

Source: Report #S254; MedMarket Diligence.

 

 

Factors Affecting Wound Healing

Coming March 2018:  Worldwide Wound Management, Forecast to 2026 more


The below is excerpted from Wound Management 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.

Wound bed preparation (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:

  • Debridement (autolytic)

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.

  • Infection/Inflammation

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.

  • Moisture balance

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.

  • Edge/Environment

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.

Extrinsic Factors

Extrinsic factors affecting wound healing include:

  • Mechanical stress
  • Debris
  • Temperature
  • Desiccation and maceration
  • Infection
  • Chemical stress
  • Medications
  • Other factors such as alcohol abuse, smoking, and radiation therapy

Mechanical Stress

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

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

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

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

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

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

Intrinsic factors that directly affect the performance of healing are:

  • Health status
  • Age factors
  • Body build
  • Nutritional status

Health Status

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.

Age Factors

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

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.

Nutritional Status

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 2026: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”. Report #S254. Available online.

Six Key Trends in Sealants, Glues, Hemostats Markets to 2022

From July 2016 published Report #S290.

Here are six key trends we see in the global market for surgical sealants, glues, and hemostats:

  1. Aggressive development of products (including by universities, startups, established competitors), regulatory approvals, and new product introductions continues in the U.S., Europe, and Asia/Pacific (mostly Japan, Korea) to satisfy the growing volume of surgical procedures globally.
  2. Rapid adoption of sealants, glues, hemostats in China will drive much of the global market for these products, but other nations in the region are also big consumers, with more of the potential caseload already tapped than the rising economic China giant. Japan is a big developer and user of wound product consumer. Per capital demand is also higher in some countries like Japan.
  3. Flattening markets in the U.S. and Europe (where home-based manufacturers are looking more at emerging markets), with Europe in particular focused intently on lowering healthcare costs.
  4. The M&A, and deal-making that has taken place over the past few years (Bristol-Myers Squibb, The Medicines Company, Cohera Medical, Medafor, CR Bard, Tenaxis, Mallinckrodt, Xcede Technologies, etc.) will continue as market penetration turns to consolidation.
  5. Growing development on two fronts: (1) clinical specialty and/or application specific product formulation, and (2) all purpose products that provide faster sealing, hemostasis, or closure for general wound applications for internal and external use.
  6. Bioglues already hold the lead in global medical glue sales, and more are being developed, but there are also numerous biologically-inspired, though not -derived, glues in the starting blocks that will displace bioglue shares. Nanotech also has its tiny fingers in this pie, as well.

See Report #S290, “Worldwide Sealants, Glues, and Hemostats Markets, 2015-2022”.

Recent Merger and Acquisition Activity in Sealants, Glues and Hemostats

Growth in sealants, glues, and hemostats markets has been strong enough for long enough to have attracted a lot of players. With growth slowing as the untapped potential is reducing more rapidly, consolidation has now appeared in the natural order of things.

Recent Merger and Acquisition Activity in Sealants, Glues and Hemostats

Original Company/ ProductAcquiring or Collaborating CompanyDate of Acquisition/Collaboration DealFinancial Details (where revealed)
Bristol-Myers Squibb/ Recothrom¨ Thrombin topical hemostatThe Medicines Company2012/2014$105 million collaboration fee
Cohera Medical/TissuGlu¨Collaboration with B. Braun Surgical S.A. to distribute in Germany, Spain and Portugal.Jan. 2015B. Braun Surgical S.A. will exclusively market and sell TissuGlu in the territories of Germany, Spain and Portugal through its existing Closure Technologies commercial teams.
Profibrix/ FibroCapsThe Medicines Company2013$90 million, with $140 million contingent upon milestones
Medafor/Arista¨ AH Absorbable Hemostatic ParticlesCR Bard (Bard Davol)2013$200 million upfront payment
Tenaxis Medical, with ArterX (among other products)The Medicines Company2014$58 million in upfront payments
The Medicines Company/ PreveLeakª (formerly known as ArterX), Raplixaª(formerly known as FibroCaps) fibrin sealant, Recothrom¨ Thrombin topical (Recombinant) sealantMallinckrodt plc2016The entire deal has a potential value of $410 million.
Xcede Technologies, Inc./Resorbable Hemostatic PatchCollaboration with Cook BiotechJan-16Signed three collaboration agreements with Cook Biotech, including a Development Agreement, a License Agreement and a Supply Agreement to complete development, seek regulatory clearance and produce XcedeÕs resorbable hemostatic patch.

Source: MedMarket Diligence, LLC; Report #S290.

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