Demand drivers for products in wound sealing, closure, hemostasis and anti-adhesion

MedMarket Diligence’s global market Report #S190 on the range of products involved in wound securement encompasses surgical sealants, high-strength medical adhesives, sutures/staples/clips, hemostatic agents and products to prevent post-surgical adhesion.

The potential impact of emerging products in this area is driven by not only caseload but by the nature of the clinical “need”, ranging from a product being critical to provide treatment for a particular indication to a need that may only be represented in perceived benefits.

We have quantified the current and future market for products in surgical wound closure, hemostasis, anti-adhesion and related applications by detailing the products on the market and under development and assessed their current and forecast utilization based on the net result of clinical need drivers and the competitive landscape into which these products may find adoption.

For the sake of characterizing the nature of the need behind possible future product adoption, we have quantified the caseload, by clinical area, relative to a spectrum of needs levels from “important and enabling” to “aesthetic and perceived benefits”.

Category I:  Important and Enabling

Important to prevent excessive bleeding and transfusion, to ensure safe procedure, and to avoid mortality and to avoid complications associated with excessive bleeding and loss of blood.

Category II: Improved Clinical Outcome

Reduces morbidity due to improved procedure, reduced surgery time, and prevention of complications such as fibrosis, post-surgical adhesion formation, and infection (includes adjunct to minimally invasive surgery).

Category III: Cost-Effective and Time-Saving

Immediate reduction in surgical treatment time and follow-up treatments.

Category IV: Aesthetic and Perceived Benefits

Selection is driven by aesthetic and perceived benefits, resulting in one product being favored over a number of medically equivalent treatments.

On this basis, see the graphic representation below, which illustrates that the majority of demand for these products arises from the fact that they improve the clinical outcome for patients. Another key element of this is that the primary clinical areas of application contributing to demand for these products is in cardiovascular, general surgery, neurology and digestive specialties.  Note, please the categories of I-IV refer to the categories described above.

sealant-product-caseload

Source: MedMarket Diligence, LLC; Report #S190.

As further indication of the value of these products is the fact that the category exhibiting the lowest level of demand is for products that offer only aesthetic or perceived benefits.

Factors Affecting Wound Healing

The prevalence of wound types, clinical practice, products, technologies, markets, market shares and companies in wound management are detailed in the 2013 MedMarket Diligence report, “Worldwide Wound Management, Forecast to 2021″, Report #S249. (See also, “Worldwide Surgical Sealants, Glues, and Wound Closure, 2013-2018″, Report #S192, published October 2014. )


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.

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 includes sutures; dressing residues; fibers shed by dressings; and foreign material 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 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 seek to remove sources of moisture, manage wound exudates, and protect skin around 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 mainly limited to those wounds and circumstances when infection risk is high, and they are rapidly discontinued in favor of less cytotoxic agents, such as saline and non-ionic 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, 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 manifest until 10-20 years after the termination 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 underlying illness.

Chronic circulatory diseases reducing 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, reducing the ability to feel pressure or pain, contributes to a tendency to ignore pressure points and avoid pressure relief strategies.

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 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.


From the March 2013 report, “Worldwide Wound Management, Forecast to 2021″, Report #S249.


See also, “Worldwide Surgical Sealants, Glues, and Wound Closure, 2013-2018″, Report #S192, published October 2014.

 

Active wound healing technologies

Interactive and bioactive wound dressings reflect the major thrust in advanced wound management developments — effective (i.e., complete and timely) wound healing demands active intervention to not just protect wounds from the elements, so to speak, but to drive processes that accelerate wound healing.

A wound is a dynamic setting in which a great number of activities are taking place and, if not actively managed, can go decidedly awry.  Many factors influence the rate of wound healing and, in some cases, may actually turn acute wounds into chronic, non-healing wounds. These factors include mechanical stress, debris, temperature, dessication and macerations, infection, chemical stress, medication, and other extrinsic factors (e.g., alcohol abuse, smoking, radiation therapy and other) as well as the patient’s existing condition (e.g., health, age, body build, nutritional status, etc.).

Therefore, even if one only considers the products in the traditional category of wound care products — wound dressings — there is a considerable number of product types that have been developed to control these processes:

  • film dressings — allow the passage of oxygen and moisture
  • foam dressings — facilitate care of delicate wounds through less frequent changes
  • hydrogels — provide benefits of moist wound healing and absorption of exudate, support autolytic debridement
  • hydrocolloids — very absorbent for wounds with high exudate, support autolytic debridement
  • alginates — conformable, provide high absorbency and support autolytic debridement
  • anti-microbial dressings — provide moist wound healing without simultaneously stimulating growth of microbes

These products operate at the low end of the intervention scale by playing the projective role of traditional wound dressings, but in a dynamic way to facilitate and/or accelerate wound healing.

A step beyond wound dressings is the growing practice of effectively replacing the damaged tissues through homograft, allograft and other skin replacements and skin substitutes.  These products may be used with or without cellular and tissue growth factors.

At the more extreme end of the scale are involved devices and equipment that aggressively alter the wound environment to accelerate healing — negative pressure wound therapy, therapeutic ultrasound, electrical stimulation and others.


Wound care is the subject of the 2013 MedMarket Diligence Report #S249, “Wound Management, Worldwide Market and Forecast to 2021: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”, described in full at link.

Skin and Skin Substitutes in Wound Management

The development of bioengineered skin was motivated by the critical need to cover extensive burn injuries in patients with insufficient skin for grafting. Bioengineered skin substitutes have also been widely used for a variety of chronic wounds with the aim of faster healing, reduced infection and better cosmetic appearance.

Bioengineered skin consists of an outer epidermal layer and/or a dermal layer (the layer of skin between the epidermis and the subcutaneous tissue) embedded into an acellular matrix (a support structure) forming a biological skin substitute.

This ‘artificial’ tissue can be grown from the patient’s own cells or from another ‘allogeneic‘ (non-self) sources. Most commercial bioengineered skin consist of sheets of cells derived from neonatal (allogenic) foreskin. Neonatal foreskin is chosen because it is a convenient source obtained from healthy babies undergoing circumcision, it has a high content of epidermal keratinocyte stem cells, the cells grow vigorously with high metabolic activity, and allergic reactions against the cells are rare.

EpidermisBioengineered skin is designed to temporarily take over the functions of the epidermis and/or dermis until the patient’s skin barrier repairs spontaneously or until definitive skin replacement is possible with a skin graft or cultured equivalent. It is thought that bioengineered skin accelerates wound healing by introducing living cells to re-establish the conditions needed for repair including moist wound environment, structural support, cytokines and growth factors to stimulate immune response and tissue regeneration.

Globally, the market for bioenegineered skin and skin substitutes stands at just under $400 million and is growing at 14% annually. Active companies in this field include: LifeCell, Organogenesis, Celadon Science, Smith & Nephew, Genzyme Biosurgery, Brennen Medical, Integra LifeSciences, Fidia Advanced Biopolymers, Healthpoint, Ortec International, and Advanced Tissue Sciences, among others.

Skin substitutes, bioengineered skin and a wide range of other established and emerging products in wound management are the subject of the 2013 MedMarket Diligence Report #S249, “Wound Management, Worldwide Market and Forecast to 2021: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World.” (See link for full details.)

Medtech fundings, July 2013

Medtech fundings for July 2013, with a big $93 funding of Hansen Medical, have risen to over $600 million. Below are the top fundings for the month thus far:

  • Hansen Medical has secured $93 million in a private funding (intravascular robotics)
  • JenaValve Technology, Inc., has raised $62.5 million (transcatheter aortic valve)
  • uniQure Biopharma has raised $58 million in debt and equity (gene therapy)
  • GI Dynamics has raised $57.6 million (obesity treatment device)
  • ReVision Optics has raised $55 million (corneal inlays)
  • ReNeuron has raised £33.2 million or $50.99 million (stem cell therapies)
  • Tengion has raised $33.6 million (organ regenerative medicine)
  • CVRx, Inc., has raised $29.6 million (device for hypertension, heart failure)
  • BioDelivery Sciences International has raised $20 million in debt funding (drug delivery technologies)
  • Neuropace, Inc., has raised $18 million (implantable devices for epilepsy, other neuro)

For the complete list of fundings, see link.

Technologies at Medtech Startups Identified in June 2013

Below is the list of technologies at medtech startups identified in June 2013 and added to the Medtech Startups Database:

  • Implantable electrospun neurosurgical meshes and tools.
  • Undisclosed technology for the treatment of aneurysm.
  • Catheter-based, self-expandable device to restore vessel/duct patency in peripheral vascular, neurology, cardiology and women’s health applications.
  • Ultrasound guidance for interventional procedures.
  • Undisclosed medical technology development.
  • Technologies for hip replacement.
  • Angiography catheters, others.
  • Neural interface research products and technologies.
  • Hip and knee implants.
  • Surgically implanted, invisible hearing aid device.
  • Undisclosed medical technology relating to allografts.
  • Developing “generic” versions of medical technology.

For a historical listing of medtech startups technologies, see link.

Medtech Fundings, June 2013

Medtech financing for the month of June is coming in at a good clip, with the total for the month at $558 million. Below is illustrated the ranking of fundings by company for the month through June 25.

June 2013 Medtech Fundings To Date

Fundings-June-25-2013

Source: Compiled by MedMarket Diligence, LLC

The complete list of fundings in June 2013 is detailed at link.

For a historical list of fundings, see link.