From our weekly email to blog subscribers…
Extrinsic Factors Affecting Wound Healing
From 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.”
Extrinsic factors affecting wound healing include:
Mechanical stress factors include pressure, shear, and friction. Pressure can result from immobility, such as experienced by a bed- or chair-bound patient, or local pressures generated by a cast or poorly fitting shoe on a diabetic foot. When pressure is applied to an area for sufficient time and duration, blood flow to the area is compromised and healing cannot take place. Shear forces may occlude blood vessels, and disrupt or damage granulation tissue. Friction wears away newly formed epithelium or granulation tissue and may return the wound to the inflammatory phase.
Debris, such as necrotic tissue or foreign material, must be removed from the wound site in order to allow the wound to progress from the inflammatory stage to the proliferative stage of healing. Necrotic debris includes eschar and slough. The removal of necrotic tissue is called debridement and may be accomplished by mechanical, chemical, autolytic, or surgical means. Foreign material may include sutures, dressing residues, fibers shed by dressings, and foreign material which were introduced during the wounding process, such as dirt or glass.
Temperature controls the rate of chemical and enzymatic processes occurring within the wound and the metabolism of cells and tissue engaged in the repair process. Frequent dressing changes or wound cleansing with room temperature solutions may reduce wound temperature, often requiring several hours for recovery to physiological levels. Thus, wound dressings that promote a “cooling” effect, while they may help to decrease pain, may not support wound repair.
Desiccation of the wound surface removes the physiological fluids that support wound healing activity. Dry wounds are more painful, itchy, and produce scab material in an attempt to reduce fluid loss. Cell proliferation, leukocyte activity, wound contraction, and revascularization are all reduced in a dry environment. Epithelialization is drastically slowed in the presence of scab tissue that forces epithelial cells to burrow rather than freely migrate over granulation tissue. Advanced wound dressings provide protection against desiccation.
Maceration resulting from prolonged exposure to moisture may occur from incontinence, sweat accumulation, or excess exudates. Maceration can lead to enlargement of the wound, increased susceptibility to mechanical forces, and infection. Advanced wound products are designed to remove sources of moisture, manage wound exudates, and protect skin at the edges of the wound from exposure to exudates, incontinence, or perspiration.
Infection at the wound site will ensure that the healing process remains in the inflammatory phase. Pathogenic microbes in the wound compete with macrophages and fibroblasts for limited resources and may cause further necrosis in the wound bed. Serious wound infection can lead to sepsis and death. While all ulcers are considered contaminated, the diagnosis of infection is made when the wound culture demonstrates bacterial counts in excess of 105 microorganisms per gram of tissue. The clinical signs of wound infection are erythema, heat, local swelling, and pain.
Chemical stress is often applied to the wound through the use of antiseptics and cleansing agents. Routine, prolonged use of iodine, peroxide, chlorhexidine, alcohol, and acetic acid has been shown to damage cells and tissue involved in wound repair. Their use is now primarily limited to those wounds and circumstances when infection risk is high. The use of such products is rapidly discontinued in favor of using less cytotoxic agents, such as saline and nonionic surfactants.
Medication may have significant effects on the phases of wound healing. Anti-inflammatory drugs such as steroids and non-steroidal anti-inflammatory drugs may reduce the inflammatory response necessary to prepare the wound bed for granulation. Chemotherapeutic agents affect the function of normal cells as well as their target tumor tissue; their effects include reduction in the inflammatory response, suppression of protein synthesis, and inhibition of cell reproduction. Immunosuppressive drugs reduce WBC counts, reducing inflammatory activities and increasing the risk of wound infection.
Other extrinsic factors 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.
Source: “Wound Management to 2024”, Report #S251.
Source: “Global Market Opportunities in Peripheral Arterial and Venous Stents, Forecast to 2020”, Report #V201.
It was once quite convenient for manufacturers of deluxe medical widgets to worry only about other manufacturers of deluxe medical widgets. Manufacturers must now widen their perspective to consider current and future competition (and opportunity) from whatever direction it may come. –> Just thought I might chime in and suggest that, if you do make such widgets, it might be a good idea to maybe throw at least an occasional sidelong glance at biotech. (Most of you are, great, but some of you think biotech is too far away to compete…)
Organ Bioengineering is years away and poses little challenge to medical devices …FALSE. Urinary bladders have been engineered for pediatric applications. Bioengineered skin (the “integumentary” organ) is now routinely bioengineered for burns, chronic wounds, and other wound types. Across a wide range of tissue types (bone, cardiac, smooth muscle, dermal, etc.) scientists — clinicians — have rapidly developed technologies to direct the construction and reconstruction of these tissues and restore their structure and function.
Cell Biology. Of course cells are engineered into tissues as part of the science of tissue engineering, but combine this with advances in engineering not just between cells but between cells AND within cells and (…sound of my head exploding). With the sum of the understanding and capacity to control we have gained over cellular processes over the past few decades now rapidly accelerating, medical science is fast approaching the point at which it can dictate outcomes for cell, tissues, organs, organ systems, and humans (I am not frightened, but excited, with caution). Our understanding and proficiency gained in manipulating processes from cell division to pluripotency to differentiation to senescence to death OR NOT has profound consequences for fatal, debilitating, incurable, devastating, costly, and nearly every other negative superlative you can conceive.
CRISPR*: This is a new, relatively simple, but extraordinary tool allowing researchers or, more importantly, physicians to potentially swap out defective genes with healthy ones. See Nature.
(* clustered regularly interspersed short palindromic repeats)
Biotech has, over its history, often succeeded in getting attention, but has had less success justifying it, leaving investors rudely awakened to its complexities. It has continued, however, to achieve legitimately exciting medical therapeutic advances, if only as stepping stones in the right direction, like mapping the human genome, the development of polymerase chain reaction (“PCR”), and biotech-driven advances in molecular biology, immunology, gene therapy, and others, with applications ripe for exploitation in many clinical specialties, Sadly, the agonizing delay between advanced and “available now” has typically disappointed manufacturers, investors, clinicians and patients alike. CRISPR and other tools already available (see Genetic Engineering News and others) are poised to increase the expectations – and the pace toward commercialization – in biotechnology.
Vaccines and Infectious Disease: Anyone reading this who has been under a rock for lo these many years, blissfully ignorant of SARS, Ebola, Marburg, MRSA, and many other frightening acronyms besides HIV/AIDS (more than enough for us already) should emerge and witness the plethora of risks we face (and self-inflict through neglect), any one of which might ultimately overwhelm us if not medically then economically in their impacts. But capitalists (many altruistic) and others have come to the rescue with vaccines such as for malaria and dengue-fever and, even, one for HIV that is in clinicals.
Critical Mass, Synergies, and Info Tech. Biotechnology is succeeding in raising great gobs of capital (if someone has a recommended index/database on biotech funding, let me know?). Investors appear to be
forgetful increasingly confident (in the 1990s, I saw big layoffs in biotech because of ill-advised investments, but that was then…) that their money will result in approved products with protected intellectual property and adequate reimbursement and manageable costs in order to result in attractive financials. The advances in biological and medical science alone are not enough to account for this, but such advances are almost literally being catalyzed by information technologies that make important connections faster, yielding understanding and new opportunities. The net effect of individual medically-related disciplines (commercial or academic) advancing research more efficiently as a result of info tech and info sharing/synergies between disciplines is the expected burst of medical benefits ensuing from biotech. (Take a look also at Internet of DNA.)
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
Source: Report #S251.
Global Wound Management Market, Sales, 2015 & 2024
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
Source: Report #S251.
If you would like excerpts from this report, Click Here!
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
Total Wound Care Market as Percent of Entire Market, 2024
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.
Bioengineered skin, skin substitutes, foam dressings, hydrocolloids, and growth factors are among top growth segments in a global market for advanced wound management that is otherwise modest in growth, but high in volume.
The 2016 global wound management market will hit nearly $15 billion. With sales growing at just better than 5% annually on population growth, migration of technologies to developing markets, and increased per capita utilization, the aggregate market is stably tied to persistent caseload. This regular, high volume of wound product sales supports a steady stream of innovation intended to gain even the smallest edge in share, an advantage that gains its value in real terms from the multiple of such a large global caseload.
In a market in which autografts and allografts have long been common, the development of cost-effective and safe bioengineered skin and skin substitutes is finding ready adoption in wounds of all types, but particularly burn wounds.
Due to their small base of existing sales thus far, even incremental expansion of sales in the use of biological growth factors in wound management reflects high growth through the forecast period.
Biotech need not be behind the higher growth in wound management technologies. Excellent growth prospects are also seen in foams, hydrogels, hydrocolloids, and other dressing materials.
Physical systems, including negative pressure wound devices, are not demonstrating growth prospects as good as traditional wound dressing products, let alone advanced wound products.
In short, the large global market is stable and growing at best modestly, but within this market, advanced wound management technologies’ sales are accelerating at the expense of traditional wound products. Growth in wound management is clearly coming from within.
Advanced Wound Care Sales, 2014 & 2024
Source: MedMarket Diligence, LLC; Report #S251.
Fundings for medical technology reached $594 million for the month of October 2015. These are the technologies gaining funding In October 2015:
- Tissue engineering in blood vessels, including for acellular vessels use for vascular access in ESRD
- Magnetically adjustable spinal bracing system
- Technologies to reduce the risk of stroke in transcarotid artery revascularization
- Technologies to treat hearing loss
- Surgical adhesives and sealants
- Drug-device for novel treatment of urologic diseases
- Drug delivery device technology
- Minimally invasive device for the treatment of acute decompensated heart failure
- Diagnostics for acute kidney injury
- Catheter-based, minimally invasive treatment of endovascular arteriovenous fistula
- Minimally invasive, non-surgical technology for circulatory support
- Endovascular aortic aneurysm repair
- Non-invasive intracranial pressure measurement
- Implantable pump technology for fluid management
- Intraoperative imaging and navigation
- Devices for dry eye, glaucoma, others.
- Nonsurgical device for the treatment of chronic nasal obstruction
- Focused ultrasonic surgical devices for hemostasis, cauterization, and ablation
- Technology for drug delivery to brain
- Technologies for robotically-assisted minimally invasive surgery
- Catheter based therapeutic devices for the treatment of cerebral aneurysms
- Neuromodulation technologies
- Renal denervation
- Device to provide rapid allergy relief and device to monitor neonatal end-tidal carbon monoxide
For details on these, including the companies and their funding amounts, see link.
From 2010 to present (Oct 2015), as included in the Medtech Startups Database, MedMarket Diligence identified 442 new (under one year old) medical technology startups whose businesses encompass, alone or in combination, medical devices, diagnostics, biomaterials, and the subset of both biotech and pharma that is in direct competition with medical devices, including tissue engineering and cell therapy. Of these, 74% were founded in the U.S., 5% were founded in Israel, and the rest were founded in 18 other countries.
Companies in the database have been categorized by clinical and/or technology area of focus, with multiple categories possible (e.g., minimally invasive and orthomusculoskeletal and surgery). Below is the composition of the companies identified from Jan. 2010 to Oct. 2015.
Source: Medtech Startups Database
Below is a graphic on the companies by country. The U.S. (not shown) led with 327 companies.
Source: Medtech Startups Database
In the U.S., the breakdown by state, other than California and its 466 companies (excluded only to show states with significantly lower numbers), is as follows:
Source: Medtech Startups Database
Fundings for medical technologies in April 2015 reached $615 million, led by the huge $225 million funding of Intarcia Therapeutics.
Below are the top fundings for the month.
|Intarcia Therapeutics has raised $225 million in a round of funding according to the company||Subcutaneous, osmotic pump for drug delivery in type 2 diabetes|
|Mesoblast has raised $58.5 million in a round of funding by Celgene Corp.||Precursor and stem cells for cell therapy|
|MyoKardia, Inc., has raised $46 million in a round of funding according to a regulatory filing||Genetically based treatments for cardiomyopathies|
|Scanadu has raised $35 million in a Series B round of funding according to press reports||Device that enables patients to scan and upload diagnostic information|
|Neuronetics, Inc., has completed a $34.3 million Series F funding round, according to the company||Transcranial magnetic stimulation for the treatment of depression|
|Lombard Medical, Inc., has raised $26 million in financing from Oxford Finance, LLC||Stent grafts for treatment of abdominal aortic aneurysm|
|EBR Systems, Inc., has raised $20 million in a round of funding according to the company||Wireless cardiac pacing|
For the complete list of medtech fundings in April 2015, see link.
For a historical list of the individual fundings in medtech, by month, since 2009, see link.