Sutures, Staples and Other Fading Technologies

See Report #S192, “Worldwide Surgical Sealants, Glues, and Wound Closure Markets, 2013-2018”. (Note: This report has been superceded by the August 2016 Report #S290.)

Sutures have been in use for potentially thousands of years, and staples for the last several decades. Both have been frequently been the target of new development in wound closure and management, with competition in the form of advanced wound closure, whether surgical sealants, glues, hemostats, and even other mechanical wound closure. Novel wound closure technologies have decidedly gained enough credibility in clinical practice to displace volume in sutures and staples.

Sutures and Staples Are Not Fading…

Manufacturers of sutures and staples have not sat idly and watched their share erode. Indeed, the development of bioresorbable sutures and other novel suture types, the development of sophisticated stapling and suturing endoscopic instrumentation and other developments have begun to erode the share loss. Consequently, the shift “away” from sutures and staples has ebbed, such that the aggregate swing in market shares is no more than 3% compared to the swing projected three years ago of nearly 7% (see link).

Sutures and Staples in Wound Closure (excerpt from Report #S192)

The vast majority of sutures, staples, and endostaples are used to close procedures involving acute surgical wounds. Typically, chronic wounds do not involve the use of sutures and staple products unless some degree of surgical intervention is employed to remove necrotic tissue or to create a new acute wound bed to aid healing.

Sutures are classified as absorbable or non-absorbable; monofilament, multifilament or braided; and natural or synthetic. Absorbable or non-absorbable describes the suture’s effective life within tissue. Absorbable sutures lose the majority of their tensile strength within 60 days after use. Non-absorbable sutures are resistant to living tissue and do not break down. Monofilament, multifilament, and braided describe the structure or configuration of the suture based on the number of strands used to manufacture the product. Natural or synthetic refers to the origin of the suture. Natural suture materials include surgical gut, chromic gut, catgut and silk. Catgut is made from the natural collagen fibers found in the intestine of sheep, goats, cattle, hogs and horses. (It was never made from the gut of cats.) It is debatable whether catgut should continue to be used for suturing wounds, since cotton is cheaper and cotton or synthetic threads are less likely to cause infection. Synthetic suture materials include nylon, polyester, stainless steel, polypropylene, polyglycolic acid (PGA), polyglycolide-co-caprolactone (PGCL), and polydioxanone.

Suture products consist of two component parts, the needle and the suture. These can be found in a wide range of sizes and types, made of a range of materials, and the method of attachment of the suture to the needle can involve a variety of methods. Sutures are divided into braided and monofilament categories. Braided sutures are typically more pliable than monofilament and exhibit better knot security. Monofilament sutures are wirier and may require a more secure knot; however, they cause less tissue drag than braided sutures, a characteristic that is especially important in cardiovascular, ophthalmic and neurological surgery

Stapler devices are an evolution of suture technology. The goal of stapler products is to avoid infection and make the wound closure procedure easier and faster.  Staples are made of stainless steel and biomaterials and are used to join internal tissues, reconstruct or seal off organs, remove diseased tissue, occlude blood vessels, and close skin incisions and lacerations. They are primarily used during surgery as internal and/or external closure devices.

Staples are available in an assortment of sizes and features and stapler devices have been developed for specific procedures as well as for multiple uses.

Internal staplers are used to approximate (or close) internal tissues and organs. The devices may be reusable or disposable. Some disposable staplers may be reloaded several times during the course of a single patient surgical procedure, before being discarded.

The most recent internal staplers are used to perform minimally invasive surgical procedures. These allow the surgeon to endoscopically secure internal wounds instead of having to operate through an open procedure. Moreover, internal biodegradable staples obviate the need for staple removal. Such staples are ideally suited to laparoscopic surgery and are delivered via procedure-specific laparoscopic instruments. However, most staples are still made of stainless steel and when used for internal stapling procedures, whether open or laparoscopic, are not removed after healing. Skin staples are removed after the incision is healed.

Probably the major benefit of staples is that they can be applied more rapidly than sutures and can be placed precisely without requiring the skill necessary for suturing. This also means increased safety for the patient, and patients can often be discharged more rapidly if procedures are stapled rather than sutured.

While cosmetically acceptable results are usually obtained, staplers normally are not used in highly visible areas such as the face. Here, surgeons will still close by hand to minimize any scarring. In many skin closure procedures, sutures have begun to be replaced by cyanoacrylate glues. However, the ideal alternative to suturing has not yet been developed; for example, cyanoacrylate glues used for external skin closure are only one-fifth as strong as sutures.

Surgical Sealants, Glues, and Hemostats: Bioactive, Nonactive, Matrices/Scaffolds

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

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

Sealants and glues 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.

  • Products containing biologically active agents (e.g., Baxter Tisseel, Bristol-Myers Squibb Recothrom)
  • Products made from natural and synthetic (nonactive) components (e.g., Baxter CoSeal, Cohera Sylys)

  • Nonactive scaffolds, patches, sponges, putties, powders, and matrices used as surgical hemostats (e.g., Beekin Biomedical NuStat, Equimedical Equitamp)
RevMedX XStat

 

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

Bioactive and Synthetic Sealants in Wound Closure

The following is excerpted from sections of Report #S192, “Worldwide Surgical Sealants, Glues, and Wound Closure Markets, 2013-2018”, published by MedMarket Diligence, LLC.

Sealants and glues in wound closure may be comprised of naturally-occurring (bioactive) ingredients (including from human or animal) or may be synthetic in origin. Many bioactives are comprised primarily of fibrin sealant, give its evolutionary design in stopping bleeding and sealing wounds. Bioactive sealants offer the benefit of well documented performance with lack of toxicity, but with the existing sealants on the market, the strength of the closure provided falls somewhat short of what is needed for sealants to be used autonomously in all but the least challenging closure conditions. For this reason, a wide range of other biologically active agents with higher sealant strength are in various phases of evaluation (See “Gecko feet, mussel shells and other sticky things” at link).

Bioactive sealants that on the market and in development are detailed at link.

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 that are on the market and in development are detailed at link.

Below is the global surgical wound closure products market.

Surgical Wound Closure Products Market, by Device Segment

 

Source: MedMarket Diligence, LLC; Report #S192.

Technologies Gaining Nearly $600M Fundings in Medtech for October 2015

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.

Wound Sealing and Closure Markets by Country: Germany and United Kingdom

(Note: See the August 2016 Report #S290.)


Population differences represent a major difference between countries in the relative demand for medical products, but there remain many other differences in drivers and limiters of sales.

The markets for wound closure encompassing sutures & staples, vascular closure devices, surgical hemostats, surgical tapes, and surgical sealants & glues show distinct sensitivities country-by-country as a result of differences in:

  • Practice patterns
  • Cultural differences in perception of “wounds”
  • Reimbursement
  • Regulatory
  • Perception of new technology
  • Economics

For example, the two graphics below illustrate the wound closure markets in Germany and the United Kingdom. To have fully compared the markets in these two countries aside from differences in population, we might have presented per capita values in the sales, but even without doing so it is clear that relative sizes and growth rates in the two countries are sufficiently different to warrant attention in local efforts to market these products.

Screen Shot 2015-10-06 at 8.13.22 AM

Source: “Worldwide Surgical Sealants, Glues, and Wound Closure Markets, 2013-2018”, Report #S192; published by MedMarket Diligence, LLC. (Note: This report has been superceded by the August 2016 Report #S290.)

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

See updated analysis in Report #S290, “Sealants, Glues, Hemostats to 2022”.

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.
BaxterArtissFibrin sealant spray
BaxterTisseelBiodegradable fibrin sealant made of human fibrinogen and human thrombin. For oozing and diffuse bleeding.
BaxterFloSealHemostatic bioresorbable sealant/glue containing human thrombin and bovine-derived, glutaraldehyde-crosslinked proprietary gelatin matrix. For moderate to severe bleeding.
BaxterGelFoam PlusHemostatic sponge comprising Pfizer's Gelfoam hemostatic sponge, made of porcine skin and gelatin, packaged with human plasma-derived thrombin powder.
Behring/NycomedTachoCombFleece-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.
CSL BehringBeriplast P/Beriplast P Combi-SetFreeze dried fibrin sealant. Comprised of human fibrinogen-factor XIII and thrombin in aprotinin and calcium chloride solution.
CSL BehringHaemocomplettan P, RiaSTAPFreeze-dried human fibrinogen concentrate. Haemocomplettan (US) and RiaSTAP (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.
J&J/EthiconEvarrestAbsorbable 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.
J&J/EthiconBIOSEAL Fibrin SealantLow-cost porcine-derived surgical sealant manufactured in China by J&J company Bioseal Biotechnology and targeted to emerging markets.
J&J/EthiconEvithromHuman 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.
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.
The Medicines Company (TMC)In development: Fibropad patchFDA accepted company's BLA application for Fibrocaps in April 2014 and set an action date (PDUFA) in 2015. In November 2013, the European Medicines Agency agreed to review the firm's EU marketing authorization application. Status update in report #S192.
Vascular SolutionsD-Stat FlowableThick, but flowable, thrombin-based mixture to prevent bleeding in the subcutaneous pectoral pockets created during pacemaker and ICD implantations.

Source: MedMarket Diligence, LLC

Note: Status of products detailed in Report S192. See UPDATED analysis in 2016 report #S290. Available online.

 

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.)