Wound closure and healing via sealants, glues, hemostats in development

Natural tissue healing is a highly complex dance of processes that need to be working properly in order for the body to heal. Mammals have developed the ability to heal wounds rapidly through a cascade of processes that starts with hemostasis (blood clotting) to slow or stop the loss of blood. From the moment of injury, platelets start to aggregate, as well as starting to release cytokines, chemokines and hormones. Vasoconstriction takes place as the body tries to limit the loss of blood, and several vasoactive mediators come into play, including, norepinephrine, epinephrine, prostaglandins, serotonin, and thromboxane. Activated platelets lead to formation of a clot. Next, the inflammatory steps kick in, targeting and killing microbes and launching a natural internal debridement process, which serves to clean up any damaged tissue so that reconstruction may occur. Last in the cascade are the proliferative and maturation phases. These involve the deposition of new tissue matrix materials, and are intended to lead to reconstruction of tissue organelles and cellular structure. These healing steps actually overlap one another, and do not have strict times when each process begins or ends.

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. Factors which strongly affect wound healing include smoking, diabetes, age, oxygenation, stress, obesity, certain medications, alcoholism and nutrition.

Timescales for Development of
Sealants, Glues and Hemostat Products

screen-shot-2016-10-31-at-2-55-14-pm

Source: MedMarket Diligence, LLC; Report #S290.

While product development continues apace, and companies are launching their products in new countries, launches of actual new products has been relatively slow. This is due most likely to the highly technical (read: expensive) nature of the product development, as well as the cost and time involved in running clinical trials, and the strong patent protection which has been erected, especially by the leading companies. The need for the products is there, but the required clinical testing is putting a brake on the markets.

In July 2015, HyperBranch announced the product launch of Adherus® AutoSpray Dural Sealant in the US. FDA clearance to market the product was obtained in March 2015. The absorbable sealant is intended for use in brain surgery and is applied over the sutures for dura repair to prevent cerebrospinal fluid from leaking out of the incision site. The Adherus® AutoSpray Dural Sealant is made of two solutions: a PEG ester solution and a polyethylenimine (PEI) solution. When mixed together, the solutions combine to form a sealant gel that is applied to the incision site. According to the company, the sealant is fully absorbed in about 90 days.

Cohera Medical launched its TissuGlu® in select US cities in November 2015. At this point, TissuGlu® is available in ten cities in the USA, while B. Braun is the distributor for the product in Germany, Spain and Portugal.

Sanyo Chemical launched its first medical device, Hydrofit, in February 2014. The company obtained the approval of the medical device under the Pharmaceutical Affairs Law in December 2011, filing it as a novel surgical hemostatic agent intended for anastomosing the arterial blood and artificial blood vessel in surgical procedures. According to the company, the product will be produced by Sanyo and marketed by Terumo.

In 2014, Cohera Medical, Inc. launched Sylys Surgical Sealant, which can be used in gastrointestinal surgery to decrease anastomotic leak. In the same year, Baxter also gained the FDA permission for Tisseel® fibrin sealant, which, according to the company, is used in almost all types of surgical procedures.

Mallinckrodt will invest in the commercial launch and ongoing market development of both PreveLeak and Raplixa in FY 2016. According to the company, both products are faster to prepare and easier to use and store than competing products. PreveLeak, a surgical sealant, is allegedly more flexible than hemostasis glue products. It is indicated for use in vascular reconstructions to achieve adjunctive hemostasis by sealing areas of leakage. PreveLeak is currently marketed in Europe through distributors.

In an example of a delayed launch, CryoLife has been working towards launch of PerClot in the US, but ran into litigation trouble with Medafor, a wholly-owned subsidiary of CR Bard. In November 2015, CryoLife announced that it had entered into a resolution with Medafor to end the patent dispute in the US District Court for the District of Delaware between the companies regarding PerClot. Under terms of the resolution, all parties agreed to end the litigation, jointly dismissing all claims and counterclaims with prejudice and waiving all appeal rights in this case.  Each party is to pay its own attorneys’ fees and costs associated with the litigation.  However, the court’s preliminary injunction entered March 31, 2015 with respect to CryoLife’s marketing and sale of PerClot in the US will remain in effect until the expiration of Medafor’s US Patent No. 6,060,461 (the “‘461 Patent”) on February 8, 2019. CryoLife management says that this will not upset their plans, as CryoLife does not expect to receive FDA market approval for PerClot before 2018, if then.


From “Sealants, Glues, Hemostats to 2022” (#S290).

Medical, Surgical Sealants — Fibrin and Others

screen-shot-2016-10-26-at-2-23-29-pmFibrin is the result of the combination of solutions of thrombin and fibrinogen. This forms a clot just as in the body during the coagulation cascade. The thrombin then breaks the fibrinogen molecules into smaller bits of another blood protein, called fibrin. Fibrin molecules arrange themselves into a lattice with strands cross-linked by the blood component, Factor XIII. This resulting cross-linked net helps to stabilize the clot.

Numerous variants of fibrin sealant exist, including autologous products. Other, non-fibrin sealant types are thrombin, collagen & gelatin-based sealants.

Fibrin sealants are used in the US in a wide array of applications; they are used the most in orthopedic surgeries, where the penetration rate is thought to be 25-30%. Fibrin sealants can, however, be ineffective under wet surgical conditions. The penetration rate in other surgeries is estimated to be about 10-15%.

Fibrin-based sealants were originally made with bovine components. These components were judged to increase the risk of developing bovine spongiform encephalopathy (BSE), so second-generation commercial fibrin sealants (CSF) avoided bovine-derived materials. The antifibrinolytic tranexamic acid (TXA) was used instead of bovine aprotinin. Later, the TXA was removed, again due to safety issues. Today, Ethicon’s (JNJ) Evicel is an example of this product, which Ethicon says is the only all human, aprotinin free, fibrin sealant indicated for general hemostasis. Market growth in the sealants sector is driven by the need for improved biocompatibility and stronger sealing ability—in other words, meeting the still-unsatisfied needs of physician end-users.

The current market penetration of sealant products in the US stands at about 25% of eligible surgeries, with their largest volume of use in orthopedics.

Selected Fibrin and Other Sealant Types*

screen-shot-2016-10-26-at-2-10-21-pm

*Market status on each detailed in report S290.

Source: MedMarket Diligence, LLC; Sealants, Glues, Hemostats to 2022.

 

The Demand for Sealants, Glues, and Hemostats in 2016

The following is drawn from “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022.” Report #S290.

The need for surgical sealants, glues and hemostats is directly related to the clinical caseload and procedure volumes, as well as to the adoption of these products for multiple uses, such as the use of one product for sealing, hemostasis and anti-adhesion. It is fair to say that use of these products has become routine in the surgical suite and in other clinical locations. Procedure volumes are in turn driven by demographic forces, including global aging populations, while regulatory changes will continue to influence uptake of these products.

wound-prevalance

Source: MedMarket Diligence, LLC; Report #S290.

Medical Sealants

Fibrin sealants are made of a combination of thrombin and fibrinogen. These sealants may be sprayed on the bleeding surface, or applied using a patch. Surgical sealants might be made of glutaraldehyde and bovine serum albumin, polyethylene glycol polymers, and cyanoacrylates.

Sealants are most often used to stop bleeding over a large area. If the surgeon wishes to fasten down a flap without using sutures, or in addition to using sutures, then the product used is usually a medical glue.

Hemostatic Products

The surgeon and the perioperative nurse have a variety of hemostats from which to choose, as they are not all alike in their applications and efficacy. Selection of the most appropriate hemostat requires training and experience, and can affect the clinical outcome, as well as decrease treatment costs. Some of the factors that enter into the decision-making process include the size of the wound, the amount of hemorrhaging, potential adverse effects, whether the procedure is MIS or open surgery, and others.

Active hemostats contain thrombin products which may be derived from several sources, such as bovine pooled plasma purification, human pooled plasma purification, or through human recombinant manufacturing processes. Flowable-type hemostats are made of a granular bovine or porcine gelatin that is combined with saline or reconstituted thrombin, forming a flowable putty that may be applied to the bleeding area.

Medical Glues

Sealants and glues are terms which are often used interchangeably, which can be confusing. In this report, a medical glue is defined as a product used to bond two surfaces together securely. Surgeons are increasingly reaching for medical glues to either help secure a suture line, or to replace sutures entirely in the repair of soft tissues. Medical glues are also utilized in repairing bone fractures, especially for highly comminuted fractures that often involve many small fragments. This helps to spread out the force-bearing surface, rather than focusing weight-bearing on spots where a pin has been inserted.

Thus, the surgeon has a fairly wide array of products from which to choose. The choice of which surgical hemostat or sealant to use depends on several factors, including the procedure being conducted, the type of bleeding, severity of the hemorrhage, the surgeon’s experience with the products, the surgeon’s preference, the price of the product and availability at the time of surgery. For example, a product which has a long shelf life and does not require refrigeration or other special storage, and which requires no special preparation, usually holds advantages over a product which must be mixed before use, or held in a refrigerator during storage, then allowed to warm up to room temperature before use.

 

Sealants, Glues, Hemostats to 2022

 

Below is our bubble chart giving the segment size (bubble size and horizontal axis position) and growth (vertical axis position) of the products detailed in our 2014 report #S192.

Source: MedMarket Diligence, LLC; Report #S192 (published Oct. 2014)

Given the interest by companies actively involved in sealants, glues, and hemostats, we are publishing Report #S290 (June 2016), “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022.”

From Skitch

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 in Sealants, Glues, Hemostats, and Wound Closure is Absolute, Relative

(See the 2016 published report #S290, “Sealants, Glues, Hemostats, 2016-2022”.)

Of late, I have needed to re-emphasize the difference between absolute and relative growth in medtech markets (and its importance). So, here it is again, this time regarding surgical sealants and other wound closure products.

The lowest relative rate of growth in this industry is the well-established sutures and staples segment. Sales of these products globally, even supported by innovations in bioresorbables and laparoscopic delivery technologies, are only growing at a 5.6% compound annual growth rate from 2013 to 2018. By comparison, growth of sales of surgical glues and sealants is at 9.4% for 2013-2018.

But from an absolute sales growth point of view, sales of sutures and staples will go from $5.2 billion to $6.9 billion, or absolute growth of $1.7 billion. Simultaneously, the relatively high growth in surgical glues and sealants translates to the absolute growth from 2013 to 2018 of only $0.9 billion.

Obviously, both absolute and relative growth are of interest.

Screen Shot 2015-07-23 at 2.31.03 PM

Source: MedMarket Diligence, LLC; Report #S192.

Bioactive Agents in Wound Sealing and Closure

Excerpt from Report #S192, “Worldwide Surgical Sealants, Glues, and Wound Closure 2013-2018”.

Screen Shot 2015-03-30 at 10.14.59 AMBiologically 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.

Selected Biologically Active Sealants, Glues, and Hemostats 

CompanyProduct NameDescription/(*Status)
Asahi Kasei MedicalCryoSeal FS SystemFibrin sealant system comprising an automated device and sterile blood processing disposables that enable autologous fibrin sealant to be prepared from a patient’s own blood plasma in about an hour. Approved in the US for liver resection surgery and CE marked in Europe. Also sold in Japan and other Asian countries.
BaxterArtissFibrin sealant spray
TisseelBiodegradable fibrin sealant made of human fibrinogen and human thrombin. For oozing and diffuse bleeding.
FloSealHemostatic bioresorbable sealant/glue containing human thrombin and bovine-derived, glutaraldehyde-crosslinked proprietary gelatin matrix. For moderate to severe bleeding.
GelFoam PlusHemostatic sponge comprising Pfizer’s Gelfoam hemostatic sponge, made of porcine skin and gelatin, packaged with human plasma-derived thrombin powder.
Behring/NycomedTachoComb (sold OUS only). Manufactured by NycomedFleece-type collagen hemostat coated with fibrin glue components.
Bristol-Myers Squibb/ZymoGenetics (sold by The Medicines Company in the US and Canada)RecothromFirst recombinant, plasma-free thrombin hemostat; approved in US in 2008.
CSL BehringBeriplast P/Beriplast P Combi-Set (sold OUS only)Freeze dried fibrin sealant. Comprised of human fibrinogen-factor XIII and thrombin in aprotinin and calcium chloride solution.
Haemocomplettan P, RiaSTAPFreeze-dried human fibrinogen concentrate.
Haemocomplettan is sold in US and RiaSTAP is on the market in Europe.
J&J/EthiconEvicelEvicel is a new formulation of the previously available fibrin sealant Quixil (EU)/Crosseal (US). Does not contain the antifibrinolytic agent tranexamic acid, which is potentially neurotoxic, nor does it contain synthetic or bovine aprotinin, which reduces potential for hypersensitivity reactions.
EvarrestAbsorbable fibrin sealant patch comprised of flexible matrix of oxidized, regenerated cellulose backing under a layer of polyglactin 910 non-woven fibers and coated on one side with human fibrinogen and thrombin. FDA approved December 2012.
BIOSEAL Fibrin SealantLow-cost porcine-derived surgical sealant manufactured in China by J&J company Bioseal Biotechnology and targeted to emerging markets.
EvithromHuman thrombin for topical use as hemostat. Made of pooled human blood.
Pfizer/King PharmaceuticalsThrombin JMIBovine-derived topical thrombin hemostat.
Stryker/OrthovitaVitagel SurgicalBovine collagen and thrombin hemostat.
Takeda/NycomedTachoSilAbsorbable surgical patch made of collagen sponge matrix combined with human fibrinogen and thrombin. FDA approved as adjunct to hemostasis in cardiovascular surgery. This is the latest version of TachoComb (see above).
Teijin Pharma Ltd/Teijin Group (Tokyo, Japan)KTF-374Company is working with Chemo-Sero-Therapeutic Research Institute (KAKETSUKEN) to develop a sheet-type surgical fibrin sealant. Product combines KAKETSUKEN’s recombinant thrombin and fibrinogen technology with Teijin’s high-performance fiber technology to create the world’s first recombinant fibrin sealant on a bioabsorbable, flexible, nonwoven electrospun fiber sheet.
The Medicines Company (TMC)Raplixa (formerly Fibrocaps)Sprayable dry-powder formulation of fibrinogen and thrombin to aid in hemostasis during surgery to control mild or moderate bleeding.
In development: Fibropad patchFDA accepted company’s BLA application for Fibrocaps in April 2014 and set an action date (PDUFA) of January 31, 2015. In November 2013, the European Medicines Agency agreed to review the firm’s EU marketing authorization application. Company anticipates US and European launch in early to mid-2015.
Vascular SolutionsD-Stat FlowableThick, but flowable, thrombin-based mixture to prevent bleeding in the subcutaneous pectoral pockets created during pacemaker and ICD implantations.

Note: Status of products detailed in Report #S192.

Source: MedMarket Diligence, LLC

Wound Sealant and Securement Procedure Volumes by Clinical Area and End-Point

(See the 2016 published report #S290, “Sealants, Glues, Hemostats, 2016-2022”.)

Sealants, glues, hemostats, and other products in wound closure and securement offer benefits that vary by clinical area, but the nature of that benefit also varies by the type of end-point (benefit) the product achieves — does it provide a life-saving benefit? A time-saving? Cost-savings? A cosmetic or aesthetic benefit?

Accordingly, by examining the volume of procedures for which closure and securement products provide which kind of benefit is crucial to understanding demand, especially between competitive products.

Below is a categorization of benefits ranging from the critical (I) to the aesthetic (IV).

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

Screen Shot 2015-06-23 at 7.24.29 AM

Source: MedMarket Diligence, LLC (Report #S192)

Considering these different categories, below are the volumes of procedures distributed by category across each of the major clinical disciplines.

Surgical Procedures with Potential for the Use of Hemostats, Sealants, Glues and Wound Closure Products, Worldwide (Millions), 2014

 

 

 

 

Screen Shot 2015-06-23 at 7.28.36 AM

Source: MedMarket Diligence, LLC (Report #S192)

(See the 2016 published report #S290, “Sealants, Glues, Hemostats, 2016-2022”.)

Classification of Wounds by Morphology

Wounds may be classified according to their depth and whether underlying tissues are damaged. Partial-thickness wounds do not intrude through the dermis and can heal by regeneration; full-thickness wounds involve both the epidermis and dermis, and sometimes underlying tissues as well. They generally heal by scar formation. Wound classification by morphology is shown below:

TypeTissue CharacteristicsEtiologyPrognosis for Healing
Partial thicknessInvolves entire epidermis and portions of dermis.Friction, pressure, small cuts, minor burns.Heal within 10-18 days, epidermal element germinates and migrates up to the epithelial layer. Heals without significant scarring or functional impairment.
Deep partial thicknessInvolves entire epidermis and almost entire dermis.Friction, cuts, significant burns.Healing within 20-35 days.
Full thicknessInvolves epidermis and dermis; may extend into subcutaneous tissue. Sweat glands and hair follicles are destroyed.Severe deep cuts, surgical incisions, most chronic wounds, and third-degree burns.Heals by granulation, formation of new blood vessels, new biomaterial deposition, and new cells over many weeks. Scarring usually results.
Underlying tissue damageConsidered more extensive than full- thickness wounds. Involves subcutaneous tissue, muscle, fascia, bone, and other organs.Surgery of organs, electrical burns and certain thermal burns, such as molten metal or severe scalding, massive traumatic injury, and untreated chronic damage.May require debridement or removal of all necrotic tissue to expose viable bleeding tissue. Systemic antibiotic therapy and grafts/flap skin replacement.

Source: MedMarket Diligence, LLC

The global wound management market is the subject of Report #S249.

The global market for surgical sealants, glues, hemostats, vascular closure devices, sutures/staples, and tapes is the subject of Report #S192.

See also the October 2015 report, “Worldwide Wound Management, Forecast to 2024:
Established and Emerging Products, Technologies and Markets
in the Americas, Europe, Asia/Pacific and Rest of World”, Report #S251.

Manufacturers of sealants, glues, hemostats

Sealants and glues also are emerging as important adjunctive tools for sealing staple and suture lines, and some of these products also are being employed as general hemostatic agents to control bleeding in the surgical field. Manufacturers have also developed surgical sealants and glues that are designed for specific procedures – particularly those in which staples and sutures are difficult to employ or where additional reinforcement of the internal suture/staple line provides an important safety advantage.

Surgical sealants are made of synthetic or naturally occurring materials and are commonly used with staples or sutures to help completely seal internal and external incisions after surgery. In this capacity, they are particularly important for lung, spinal, and gastrointestinal operations, where leaks of air, cerebrospinal fluid, or blood through the anastomosis can cause numerous complications. Limiting these leaks results in reduced mortality rates, less post-operative pain, shorter hospital stays for patients, and decreased health care costs.

Although some form of suturing wounds has been used for thousands of years, sutures and staples can be troublesome. There are procedures in which sutures are too large or clumsy to place effectively, and locations in which it is difficult for the surgeon to suture. Moreover, sutures can lead to complications, such as intimal hyperplasia, in which cells respond to the trauma of the needle and thread by proliferating on the inside wall of the blood vessel, causing it to narrow at that point. This increases the risk of a blood clot forming and obstructing blood flow. In addition, sutures and staples may trigger an immune response, leading to inflamed tissue that also increases the risk of a blockage. Finally, as mentioned above, sutured and stapled internal incisions may leak, leading to dangerous post-surgical complications.

These are some of the reasons why surgical adhesives are becoming increasingly popular, both for use in conjunction with suture and staples and on a stand-alone basis. As a logical derivative, surgeons want a sealant product that is strong, easy-to-use and affordable, while being biocompatible and resorbable. In reality, it is difficult for manufacturers to meet all of these requirements, particularly with biologically active sealants, which tend to be pricey. Thus, for physicians, there is usually a trade-off to consider when deciding whether or not to employ these products.

Surgical sealants, glues, and hemostats can be divided into several different categories based on their primary components and/or their intended use. For the purposes of this analysis, the market is broken down by composition into products containing biologically active agents, products made from natural and synthetic (nonactive) components, and nonactive scaffolds, patches, sponges, putties, powders, and matrices used as surgical hemostats. The market for sealants, glues, and hemostats, while largely controlled by J&J/Ethicon and Baxter, nonetheless has many active players, many of whom have demonstrated staying power (and growing share) in the global market.

Below is illustrated the manufacturers in bioactive products, non-active natural or synthetic agents, and non-active materials.
Hemostats

Source: MedMarket Diligence, LLC; Report #S192(Note: This report has been superceded by the August 2016 Report #S290.)