Growth Factors in Wound Management

Growth Factors, Production and Known Effects in Wound Healing

Growth FactorProduced byCurrently Known Effects
Epidermal Growth Factor (EGF)Platelets, macrophagesStimulates fibroblasts to secrete collagenase to degrade the matrix during the remodeling phase. Stimulates keratinocyte and fibroblast proliferation. May reduce healing time when applied topically.
Transforming Growth Factor (TGF)Platelets, macrophages, lymphocytes, hepatocytesTGF-a: Mitogenic and chemotactic for keratinocytes and fibroblasts
TGFPlatelets, macrophages, lymphocytes, hepatocytesTGF-b1 and TGF-b2: Promotes angiogenesis, up-regulates collagen production and inhibits degradation, promotes chemo attraction of inflammatory cells.
TGFPlatelets, macrophages, lymphocytes, hepatocytesTGF-b3 (antagonist to TGF-b1 and b2): Has been found in high levels in fetal scarless wound healing and has promoted scarless healing in adults experimentally when TGF-b1 and TGF-b2 are suppressed.
Vascular Endothelial Growth Factor (VEGF)Endothelial cellsPromotes angiogenesis in hypoxic tissues.
Fibroblast Growth Factor (FGF)Macrophages, mast cells, T-lymphocytesPromotes angiogenesis, granulation, and epithelialization via endothelial cell, fibroblast, and keratinocyte migration, respectively.
Platelet-Derived Growth Factor (PDGF)Platelets, macrophages, and endothelial cellsAttracts macrophages and fibroblasts to zone of injury. Promotes collagen and proteoglycan synthesis.
InterleukinsMacrophages, keratinocytes, endothelial cells, lymphocytes, fibroblasts, osteoblasts, basophils, mast cellsIL-1: Proinflammatory, chemotactic for neutrophils, fibroblasts, and keratinocytes. Activates neutrophils
InterleukinsMacrophages, keratinocytes, endothelial cells, lymphocytes, fibroblasts, osteoblasts, basophils, mast cellsIL-4: Activates fibroblast differentiation. Induces collagen and proteoglycan synthesis.
InterleukinsMacrophages, keratinocytes, endothelial cells, lymphocytes, fibroblasts, osteoblasts, basophils, mast cellsIL-8: Chemotactic for neutrophils and fibroblasts.
Colony Stimulating Factors (CSF)Stromal cells, fibroblasts, endothelial cells, lymphocytesGranulocyte colony stimulating factor (G-CSF): Stimulates granulocyte proliferation.
CSFStromal cells, fibroblasts, endothelial cells, lymphocytesGranulocyte Macrophage Colony Stimulating Factor (GM-CSF): Stimulates granulocyte and macrophage proliferation.
Keratinocyte growth factorFibroblastsStimulates keratinocyte migration, differentiation, and proliferation.

Source: “Wound Management to 2024”, Report #S251

Wound management regional growth (“rest of north america”)

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From Report S251 (see global analysis and the above detail for Americas (with detail for U.S., Rest of North America and Latin America), Europe (United Kingdom, Germany, France, Spain, Italy, and Rest of Europe), Asia/Pacific (Japan, Korea, and Rest of Asia/Pacific) and Rest of World.

Do you wish to see excerpts from “Worldwide Wound Management, Forecast to 2024: Established and Emerging Products, Technologies and Markets”?

Bioengineered Skin & Skin Substitutes in Wound Care

Bioengineered skin was developed because of the need to cover extensive burn injuries in patients who no longer had enough skin for grafting. Not so long ago, a patient with third degree burns over 50% of his body surface usually died from his injuries. That is no longer the case. Today, even someone with 90% TBSA has a good chance of surviving. With the array of bioengineered skin and skin substitutes available today, such products are also finding use for chronic wounds, in order to prevent infection, speed healing and provide improved cosmetic results.

apligraf
Apligraf, Organogenesis

Skin used in wound care may be autograft (from the patient’s own body, as is often the case with burn patients), allograft (cadaver skin), xenogeneic (from animals such as pigs or cows), or a combination of these. Bioengineered skin substitutes are synthetic, although they, too, may be combined with other products. It consists of an outer epidermal layer and (depending on the product) a dermal layer, which are embedded into an acellular support matrix. This product may be autogenic, or from other sources. Currently most commercial bioengineered skin is sheets of cells derived from neonatal allogenic foreskin. This source is chosen for several reasons: because the cells come from healthy newborns undergoing circumcision, and therefore the tissue would have been discarded anyway; foreskin tissue is high in epidermal keratinocyte stem cells, which grow vigorously; and because allergic reactions to this tissue is uncommon.

Selected Bioengineered Skin & Skin Substitutes

bio-skin

Source: Exhibit 3-16 in MedMarket Diligence, LLC, Report #S251. To get excerpts, Click Here

Bioengineered skin displacing traditional wound management products

Very decided shifts are taking place in the wound management market as advanced wound technologies take up caseload from traditional technologies like gauze and others. It becomes evident that traditional products once representing above average sales are now projected to be below average (gauze) as are even a moderately new technology, “negative pressure wound therapy devices” (NPWD), while bioengineered skin and skin substitutes will represent “above average”.

Global Wound Management Market,
Above/Below Average Sectors, 2015 & 2024

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Source: Report #S251.

Global Wound Management Market, Sales, 2015 & 2024

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Source: Report #S251.

Despite the tepid growth of traditional wound management products, they remain very large markets that even the most aggressively growing segments will require time to match that volume. Bioengineered skin and skin substitutes are moving fast in that direction.

Global CAGR 2016-2024 for Wound Management Segments

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Source: Report #S251.

If you would like excerpts from this report, Click Here.

Wound Markets East and West: A Comparison?

Placed on the same scale, U.S. markets for wound management technologies do not seem starkly different from those in the Asia/Pacific region, with insignificant differences, now and in the future, in the balance of different technologies used.

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Source: MedMarket Diligence, LLC; Report #S251.

However, one cannot really compare the U.S. and Asia/Pacific on the “same scale” without seeing the obvious differences:

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Source: MedMarket Diligence, LLC; Report #S251. If you would like excerpts from this report, Click Here.

Growth in wound management from trends in prevalence, technology

Worldwide, an enormous number of wounds are driving a $15 billion market that will soon pass $20 billion. What is driving wound sales is the continued growth and prevalence of different wound types targeted by medical technologies ranging from bandages to bioengineered skin, physical systems like negative pressure wound therapy, biological growth factors, and others.

Most attention in wound management is focused on improving conventional wound healing in difficult clinical situations, especially for chronic wounds, in the expansion of wound management technologies to global markets, and in the application of advanced technologies to improve healing of acute wounds, especially surgical wounds.

Global Prevalence of Wound Types, 2015

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Source: MedMarket Diligence LLC; Report #S251. Request excerpts from this report.

Total Wound Care Market as Percent of Entire Market, 2024

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Source: MedMarket Diligence LLC; Report #S251. Request excerpts from this report.


 

Global Wound Management Market: Segment Size, Growth to 2024

The content of this post is drawn from the complete Report #S251, “Worldwide Wound Management, Forecast to 2024: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”. For separate coverage of sealants, glues, and hemostats in wound management, see Report #S290.

The World Market for Wound Management Report encompasses twelve product segments:

  • Traditional Adhesive Dressings
  • Traditional Gauze Dressings
  • Traditional Non-Adherent Dressings
  • Film Dressings
  • Foam Dressings
  • Hydrogel Dressings
  • Hydrocolloid Dressings
  • Alginate Dressings
  • Antimicrobial Dressings
  • Negative Pressure Wound Therapy Devices
  • Bioengineered Skin & Skin Substitutes
  • Wound Care Growth Factors

The report examines North and South America, the European Union, Asia/Pacific and Rest of World, and looks at markets and growth rates by product and country for the years 2014-2024. The world market in 2024 for the total wound management market represented by the segments listed above is projected to be worth over $22 billion, with segments growing at widely variable rates, with lowest sales growth in traditional adhesive bandages and the highest sales growth in bioengineered skin and skin substitutes

Source: MedMarket Diligence, LLC; Report #S251.

Below are representative examples of each type of wound management product.

    
Dressing categoryProduct examplesDescriptionPotential applications
FilmHydrofilm, Release, Tegaderm, BioclusiveComes 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.
FoamPermaFoam
PolyMem
Biatain
Polyurethane foam dressing available in sheets or in cavity filling shapes. Some foam dressing have a semipermeable, waterproof layer as the outer layer of the dressingFacilitates a moist wound environment for healing. Used to clean granulating wounds which have minimal exudate.
HydrogelHydrosorb Gel Sheet, Purilon, Aquasorb, DuoDerm, Intrasite Gel, GranugelColloids which consist of polymers that expand in water. Available in gels, sheets, hydrogel-impregnated dressings.Provides moist wound environment for cell migration, reduces pain, helps to rehydrate eschar. Used on dry, sloughy or necrotic wounds.
HydrocolloidCombiDERM, Hydrocoll, Comfeel, DuoDerm CGF Extra Thin, Granuflex, Tegasorb, Nu-DermMade 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.
AlginateAlgiSite, Sorbalgon Curasorb, Kaltogel, Kaltostat, SeaSorb, TegagelA 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.
AntimicrobialBiatain Ag
Atrauman Ag
MediHoney
Both 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
NPWDSNa
V.A.C. Ulta
PICO
Renasys (not in USA)
Prospera PRO series
Invia Liberty
Computerized 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. Not to be used if necrotic tissue is present in over 30% of the wound.
Bioengineered Skin and Skin SubstitutesAlloDerm, AlloMax, FlexHD, DermACELL, DermaMatrix, DermaPure, Graftjacket Regenerative Tissue Matrix, PriMatrix, SurgiMend PRS, Strattice Reconstructive Tissue Matrix, Permacol, EpiFix, OASIS Wound Matrix, Apligraf, Dermagraft, Integra Dermal Regeneration Template, TransCyteBio-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

Source: MedMarket Diligence, LLC; Report #S251.

There are some market restraints at work, primarily the high cost of the new technologies. Not all country healthcare budgets can afford advanced wound care products, even if they are proven to decrease healing times and hospital costs over the longer run. The development of substitute products threatens existing product categories, while a lack of sufficient clinical and economic evidence backing new technology hinders growth and acceptance of some of the more advanced wound management technologies.

In addition, improved wound prevention and a lack of regulation on tissue engineering in the EU are also expected to hold back the development of new technologies. In addition to market restraints, there are a number of drivers that are expected to shape this market in the years to come. One of the primary drivers is the aging of the global population. 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 underlying illness. Happily, most wounds heal without any problems. However, chronic wounds may take months or years to fully close, or may never close. Chronic wounds adversely affect the individual’s quality of life, and are a leading cause of burgeoning healthcare costs. Type 2 diabetes represents 85-95% of all diabetes in developed countries, and accounts for an even higher percentage in developing countries. There were 26 million diabetic patients in the US in 2012 and 285 million patients globally.   Of these patients, approximately 15% will develop a diabetic foot ulcer and 50% of these will become infected, representing an estimated 2 million patients. Diabetic foot infections are currently treated with systemic antibiotics, but the estimated failure rate of antibiotics for diabetic foot ulcers is in excess of 22%. A patient with diabetes is at significant risk of damage to tissues caused by impaired homeostasis due to the disease process. For example there is a tendency for such tissues to develop blockages in smaller blood vessels, which reduces the ability of these vessels to provide sufficient oxygen to tissues already under stress due to compromised nutrient supply and the diabetic condition. These patients then develop arterial ulcers. They may also have a tendency to suffer from venous ulcers, due to the underlying poor condition of cells as a result of the diabetes. The diabetic foot is the most common cause of non-traumatic lower extremity amputations in the US and Europe: there is an average of 82,000 amputations per year in the U.S., costing an estimated $1.6 billion annually. The estimated cost of foot ulcer care in the U.S. ranges from $4,595 per ulcer episode to more than $28,000 and the total annual cost of foot ulcer care in the US has been estimated to be as high as $5 billion.

Pressure, or decubitus, ulcers are another of the most common types of chronic wounds. The treatment of pressure ulcers places a major burden on healthcare systems worldwide, with an emerging additional cost of litigation increasing in importance over recent years. Healthcare practitioners need to be aware of both the direct and indirect costs and consider how the implementation of prevention protocols may offer cost savings in the longer term. The cost of a dressing for example as a prevention tool is minimal in comparison to the costs of treating an established pressure ulcer. Following are a few hard numbers on the true financial cost of pressure ulceration:

  • The estimated cost to the US hospital sector is $11 billion per annum
  • The estimated cost to the UK national health service is estimated at £1.4-£2.1 billion annually (4% of total NHS expenditure)
  • Lawsuits remain common in both acute and long term care — with high payments in certain cases
  • The average cost to treat an individual with an unstageable ulcer or a deep tissue injury is estimated to be $43,180
  • The average length of stay in hospital is almost three times longer for chronic wounds
  • The mean hospital cost for management of pressure ulcers in the U.S. is $14,426. In comparison, the same cost in Korea is identified as $3,000-$7,000.

The cost of treating chronic wounds is one element driving the development and utilization of advanced wound care technologies. Other drivers are the aging of the population, and the obesity epidemic, which is expected to produce a wave of diabetics in the years to come.

Source: Report #S251.

 

Top Growth Wound Care Product Sales By Country

Whether sales growth arises by a preferred adoption of one technology over another or by better than average economic conditions — or both, sales of wound management products are driven by technology adoption rates that vary by country, clinical practice patterns, reimbursement and other variables.

We assessed current and forecast sales for the following products:

  • Traditional Adhesive Dressings
  • Traditional Gauze
  • Traditional Non-Adherent
  • Film
  • Foam
  • Hydrogel
  • Hydrocolloid
  • Alginate
  • Antimicrobial
  • Negative Pressure Wound Therapy
  • Bioengineered Skin & Skin Substitutes
  • Growth Factors

For all product segments but the traditional adhesive, gauze, and non-adherent wound care products (which were assessed only at the global level), we assessed growth in each of the following countries/regions: Americas (USA, Rest of North America, Latin America), Europe (United Kingdom, Germany, Italy, France, Spain, Rest of Europe), Asia/Pacific (Japan, Korea, Rest of Asia/Pacific), and Rest of World.

From our examination (report #S251) of the global market for wound management products, below are the top product-country cohorts in terms of projected compounded sales growth from 2015 to 2024.

Source: MedMarket Diligence, LLC; Report #S251.

 

Leaders in the global wound management market

There are literally many hundreds—perhaps thousands—of companies in wound care, ranging from tiny companies operating with a couple of employees in a developing country, to large-cap market leaders with thousands of employees located in offices around the world.

The following exhibit shows that a handful of companies account for a large part of the global advanced wound care market. Acelity LP, Inc., which is a merger of Kinetic Concepts, Inc. (KCI), Systagenix, Inc. and LifeCell, is now one of the leaders in this market, and accounts for about 20% of wound care revenues. Acelity is followed by Smith & Nephew plc, which is followed by several other companies with 13% or less of the market. The hundreds of other companies fall into the 20% of “Other”. In summary, about seven companies account for approximately 80% of the advanced wound care market worldwide.

Source: MedMarket Diligence, LLC; Report #S251.