Sealants, hemostats, glues — future markets foreseen

From our past coverage of surgical sealants, glues, hemostats in our 2014 Report #S192.  (See the forthcoming June 2016 report, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022”, Report #S290.)

Fibrin and synthetic sealants offer a significant advantage over pure hemostats because they do not rely on the full complement of blood factors to produce hemostasis. Sealants provide all the components necessary to prevent bleeding and will often prevent bleeding from tissues where blood flow is under pressure and the damage is extensive.

CryoLife
Source: CryoLife

These products have the potential to replace sutures in some cases where speed and strength of securement are priorities for the surgical procedure.

Biologically active sealants typically contain various formulations of fibrin and/or thrombin, either of human or animal origin, which mimic or facilitate the final stages of the coagulation cascade. The most common consist of a liquid fibrin sealant product in which fibrinogen and thrombin are stored separately as a frozen liquid or lyophilized powder. Before use, both components need to be reconstituted or thawed and loaded into a two-compartment applicator device that allows mixing of the two components just prior to delivery to the wound. Because of the laborious preparation process, these products are not easy to use. However, manufacturers have been developing some new formulations designed to make the process more user friendly. Leaders in biologic surgical sealant space include Baxter International and Johnson & Johnson’s Ethicon Biosurgery division, but there are a number of smaller suppliers as well, in what has become an increasingly crowded field.

Compared to biologically active sealants containing fibrin and other human- or animal-derived products, synthetic sealants represent a much larger segment of the sealant market in terms of the number of competitors, variety of products, and next-generation products in development. Non-active synthetic sealants do not contain ingredients such as fibrin that actively mediate the blood clotting cascade, rather they act as mechanical hemostats, binding with or adhering to the tissues to help stop or prevent active bleeding during surgery.

Synthetic sealants represent an active category for R&D investment in large part because they offer several advantages over fibrin-based and other biologically active sealants. First and foremost, they are not derived from animal or human donor sources and thus eliminate the risks of disease transmission. Moreover, they are typically easier to use than biological products, often requiring no mixing or special storage, and many of these products have demonstrated improved sealing strength versus their biological counterparts. Synthetic products also have the potential to be more cost-effective than their biologically active counterparts. Leaders in the synthetic surgical sealants space include Baxter International Inc., CryoLife, CR Bard, and Ethicon/J&J; however, there are many up-and-coming competitors operating in this segment of the market with some interesting next-generation technologies that could gain significant traction in the years ahead. Moreover, unlike the fibrin sealants segment, where most products have more general indications for surgical hemostasis, a good number of competitors in the synthetic sealant field are focused on specific clinical applications for their products, such as cardiovascular surgery, plastic surgery, or ophthalmic surgery.

Sealants-Hemostats-Glues-companies-by-type
Source: Report #S192 (pub. 2014)

The non-active hemostats segment of the market includes a variety of scaffolds, patches, sponges, putties, powders, and matrices made of various nonactive materials that act mechanically to stop/absorb active bleeding, often in conjunction with manual compression, during surgical procedures as well as emergency use. Many of the companies active in the first two market segments discussed above also participate in this sector, including Ethicon/J&J, CR Bard, Baxter, and CryoLife, but there are also many other companies that compete in the hemostats market worldwide.


MedMarket Diligence is completing a global analysis of medical and surgical sealants, glues, and hemostats to reveal the patterns of sales, product adoption rates, and the realized/unrealized opportunities for extant stakeholders inclusive of manufacturers, buyers, and the investment arena. Publishing in June 2016, Report #S290, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022”.

 

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 healing factors; Growth in peripheral stenting; Nanomed applications

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
Debris
Temperature
Desiccation and maceration
Infection
Chemical stress
Medications
Other factors

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.


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Source: “Global Market Opportunities in Peripheral Arterial and Venous Stents, Forecast to 2020”, Report #V201.


Selected Therapeutic and Diagnostic Applications of Nanotechnology in Medicine

Below are selected applications for neuromedical technologies in development or on the market currently.

Drug Delivery
Chemotherapy drug delivery
Magnetic nanoparticles attached to cancer cells
Nanoparticles carrying drugs to arterial wall plaques
Therapeutic magnetic carriers (TMMC) [guided using magnetic resonance navigation, or MRN]

Drugs and Therapies
Diabetes
Combatting antimicrobial resistance
Alzheimer’s Disease
Infectious Disease
Arthritis

Tissue, cell and genetic engineering involving nanomedical tools
Nanomedical tools in gene therapy for inherited diseases
Artificial kidney
ACL replacements
Ophthalmology
Implanted nanodevices for alleviation of pain

Biomaterials 

Nanomedicine and Personalized Treatments

Source: Report #T650, “Global Nanomedical Technologies, Markets and Opportunities, 2016-2021”. Report #T650.

Cerebral thrombectomy systems

Selected Cerebral Thrombectomy Systems on the U.S. and International Markets

From the 2015 report, “Emerging Global Market for Neurointerventional Technologies in Stroke, 2014-2019”.

CompanyDeviceFeaturesVessel RangeDevice Sizes (D/L)Regulatory Status
AcandisAperioSelf-expanding nitinol stent-based device with hybrid cell design and adaptable working length1.5 to 5.5 mm3.5, 4.5, 6.0 mm / 28, 30 or 40 mmCE Marked
BALTCatch+ Mini/, Catch+, Catch+ Maxi, Catch+ MegaSelf-expanding 16-wire nitinol baskets with tapering cell size design, closed distal tip and 3 distal-1 proximal radiopaque markers2.0 to 7.0 mm3.0, 4.0, 6.0, 9.0 mm / 15, 20, 30, 55 mmCE Marked
Codman /DePuyRevive SESelf-expanding nitinol basket with hybrid cell design, closed distal tip, and 3 radiopaque markers1.5 to 5.5 mm2.5, 3.0, 3.5, 4.0, 5.0, 6.0 mm / 20, 30, 40 mmCE Marked, Approved in China, South Korea, and Taiwan
CovidienSolitaire FRSelf-expanding nitinol stent-based device with Parametric design (for multiple planes of clot contact to enhance capture). Features 3 or 4 distal and 1 proximal markers2.0 to 5.5 mm4.0, 6.0 mm /26, 31, 42 mmCE Marked, FDA approved
NeuraviEmbotrapSelf-expanding nitinol stent-based device with open cell design, closed distal tip, and 3 radiopaque markers. Features dilating inner channel for rapid flow restoration and integrated distal and side branch protection2.0 to 5.5 mm3.0, 4.0, 6.0 mm / 15, 20, 30, 55 mmCE Marked
PenumbraPenumbra SystemAspiration based system comprised of vacuum pump, specialty clot capture & retrieval catheters, and Separator> 3 mm3.0, 4.0, 5.0 mm / 26 mmCE Marked, FDA approved, available in Asia, Australia, and South America
PhenoxpREsetSelf-expanding nitinol stent-based tapering device with closed ring design, and stable proximal opening2.0 to 4.0 mm4.0, 6.0 mm / 30, 45 mmCE Marked
StrykerTrevo Pro, Trevo View, Trevo XPLine of self-expanding nitinol stent-based devices (standard, all radiopaque, oversized) with spiral cell design and soft, guidewire-like closed distal tip1.5 to 4.0 mm4.0, 5.0, 6.0 mm / 20, 30, 40 mmCE Marked, FDA approved

Source: MedMarket Diligence, LLC; Report #C310.

Surgical Procedures with Potential for Sealants, Glues, Hemostats

Sealants, glues, and hemostats must offer benefit to be adopted in clinical practice, or surgical procedures. Benefits can fall into a number of categories. These range from preventing serious complications from surgery (blood loss), improved patient outcomes (fewer complications, reduction in repeats), reductions in procedure time or other time- or cost-saving benefits, or improved aesthetic and perceived benefits. See these detailed below.

Criteria for Adjunctive Use of Hemostats, Sealants, Glues and Adhesion Prevention Products in Surgery

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Source: MedMarket Diligence, LLC; Report#S192.

We have assessed surgical sealants, glues, and hemostats for their potential in general surgery, aesthetics, neurology, urological, gastroenterology, orthopedics, and cardiovascular medicine.

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Source: MedMarket Diligence, LLC; Report #S192, “Worldwide Surgical Sealants, Glues, and Wound Closure Markets, 2013-2018”.


See the forthcoming report #S290, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022: Established and Emerging Products, Technologies and Markets in the Americas, Europe, Asia/Pacific and Rest of World”.  (Contact us for details to acquire the 2014 report #S192 and the new report, #S290, for a combined price before S290 publishes.)

 

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”?

Stents: From Peripheral Arterial to Peripheral Venous

Interventional technologies are expanding in all directions and vasculatures. Peripheral stenting as part of endovascular aortic repair or treatment of other symptomatic peripheral artery disease also include bare metal and drug-eluting stents for critical limb ischemia resulting from iliac, femoropopliteal and infrapopliteal occlusive disease; stent-grafting devices used in endovascular repair of abdominal and thoracic aortic aneurysms; as well as a subset of indication-specific and multipurpose peripheral stents used in recanalization of iliofemoral and iliocaval occlusions resulting in CVI.

Despite similarities in market dynamics (a notable difference here is the higher growth rate of venous stents)…

Screen Shot 2016-03-21 at 9.36.37 AM

Source: MedMarket Diligence, LLC; Report #V201.

…venous markets have not yet reach the same scale as arterial stents (now shown on the same scale):

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Source: MedMarket Diligence, LLC; Report #V201.

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.


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