Gauze dressings, bioengineered skin, alginates, negative pressure devices, cellular growth factors, hydrogels, antimicrobial dressings — all of these products (and more) represent the practice of wound management for the entire spectrum of wound types and severities.
Practice patterns, regulatory requirements, price pressures, healthcare delivery system gatekeepers, demographics, cultural sensitivities — all of these represent a sampling of the different forces that dictate the size and outlook of the markets for different wound management products in global markets.
It’s no surprise, then, that product sales are growing (or declining) at different rates in different regions of the world, but the data is clear on this. MedMarket Diligence researched and published this data in its global wound management market Report #S249, which details the clinical practice of wound management, the products on the market and in development, the current and forecast markets for each worldwide and regionally and the competitors vying for market presence now and in the future. Research from primary and secondary sources, the global wound market data illustrated above (which is also detailed by country) and presented in Report #S249 is a compelling read for market participants.
Wound management is a field and an industry in a constant state of flux. With so many different technologies involved in addressing wounds, from the chronic to the acute, with technologies from the very well established to the cutting-edge new, the balance of product utilization (and manufacturer revenues) is a constantly moving target.
Traditional wound dressings — simple gauze or other inert bandages — represent a huge existing market by virtue of their broad clinical utility and well established presence in the market (literally, centuries), while novel technologies like growth factors, which have just begun to demonstrate their potential to accelerate healing and/or solve the vexing problem of chronic wounds, have not really begun to penetrate clinical practice and generate substantial caseloads, yet. Between the extremes is a continuous range of products across the spectrum from the established to the novel.
Below is illustrated the 2012 to 2021 shift in the balance of the global wound management products market for the specific product types. The aggregate market is growing over this period at a respectable +7% CAGR, but that aggregate rate belies the individual segment rates ranging from a low of under 2% to a high of over 27%. That makes these share values all the more intriguing.
Surgical closure and securement products range from simple suture products to sophisticated biomaterial aids for hemostasis, sealant activity, and for adhesion prevention. Within the hemostasis field, products have the objective of rapidly achieving hemostasis and acting to seal in the presence of high pressure blood flow or air flow.
Natural hemostats such as gelatin, collagen and thrombin were first developed as hemostatic agents, followed by mixes and fibrin sealants. More recently, companies have introduced synthetic sealants and hemostats that accelerate the process of blood clotting and provide a stronger seal that will withstand greater pressures. These products employ various synthetic polymer chemistry systems. Glues are required to secure tissue firmly under substantial forces. In extreme cases such as musculoskeletal repair, these glues need to withstand high tension and pressure forces. Fibrin and other sealants are not strong enough for these applications and have been used as adjuncts to sutures and staples. Cyanoacrylate glues have sufficient strength for most procedures but are not yet cleared for use in the majority of internal applications due to toxicity concerns. They also lack sufficient flexibility for use in many procedures.
Efforts are progressing to develop new biomaterials capable of gluing tissues with high strength, low toxicity, and sufficient flexibility to avoid breakage of the bond. In addition, cyanoacrylate manufacturers are examining the possibility of improving cyanoacrylate technology to overcome the existing challenges of toxicity and brittleness. Despite this huge challenge, one or both of these two approaches are likely to establish new products in the next decade. In addition, the evidence of research work suggests it should be possible to create a glue technology that incorporates hemostatic properties to further enhance the role of this technology.
Apart from fibrin-based sealants and cyanoacrylate-based high-strength glues, there are three other main categories of closure/attachment products in use or in development at present.
Collagen and Thrombin Combination Collagen is a major protein found in most mammals; the form of collagen that is generally used for wound sealant and closure is a white water-soluble fiber containing several key amino acids. In most sealants, collagen forms a matrix on which thrombin (but also fibrin, polyethylene glycol (PEG) polymers, or other compounds) are attached. The role of the collagen matrix is to channel blood with its various clotting proteins to the compounds attached to the matrix (thrombin, etc.), triggering a clotting cascade.
Polyethylene Glycol Polymer (PEG) Polymers such as polyethylene glycol polymer (PEG) can absorb fluids and are the basis for products to seal and join tissues. CoSeal (Angiotech Pharmaceuticals, marketed by Baxter BioSurgery) and FocalSeal (Genzyme) are two products of this type. They are completely synthetic and offer quick sealing of the wound with the flexibility to expand and contract. Because these sealants are synthetic, they do not pose the risk of viral infection spreading from one person to another.
Albumin Cross-Linked with Glutaraldehyde Albumin, the protein that forms egg white, is one of the strongest natural adhesives in the market. Albumins are water-soluble and will coagulate when heated or combined with certain acids. When combined with glutaraldehyde, albumin forms a strong adhesive for internal surgery. The albumin/glutaraldehyde compound forms a cross-link with the tissues to be bonded that can even be stronger than the underlying tissues. In fact, the compound has been shown to withstand pressures of 500 mm–800 mm of mercury, which is more than four times normal human blood pressure.
CryoLife’s BioGlue is a widely used albumin/glutaraldehyde glue. It begins to set within 20–30 seconds of application and reaches its ultimate bonding strength within two minutes.
It is unlikely that any one formulation of tissue glue will be adequate for all applications. For example, fixing fragments of bone after significant bone trauma is likely to require an adhesive with a different modulus and strength to that required for adherence of pericardium during cardiovascular surgery. It is also likely that the sealant and hemostatic properties of these two products will need to be different. For example, to stick pericardial tissues together, the surgeon will be concerned with avoiding surgical adhesions and excessive fibrosis that might lead to problems during revision surgery. In the example of bone repair, rapid rehabilitation and avoidance of non-unions during fracture healing is a major challenge: this would suggest looking for a glue that encourages osteoblast activity and does not form an impenetrable barrier for cellular in- growth, but which can also tolerate the static and dynamic forces put upon bone.
Recently, new technologies have appeared on the market to address the need for adhesion prevention. These products have been formulated to be approvable by the FDA through device regulation routes; thus, in addition to providing a physical barrier, these products also may have some subsidiary active mechanism to achieve their objective.
In parallel with new products, in several instances new delivery systems have had to be developed. Surgeons also experiment with these products in an effort to produce superior results. A surgeon may, for example, mix a sealant with a few ml of saline to gain greater control over product application. Development of these delivery systems may be driven by several factors, such as: to improve the speed and ease of surgical procedures; to facilitate complex procedures that would otherwise be less successful; to better access a particular tissue; or to avoid premature mixing of two components, thus providing better control of the gluing process. New delivery systems have evolved to spray liquid hemostat solutions such as thrombin onto surgical sites to improve speed of hemostasis. Fibrin sealant is supplied as two powders that need to be solubilized and then mixed immediately prior to application to the surgical site. This has led to the development of a number of sophisticated medical delivery devices, and companies like Baxter aredeveloping single component systems that are already solubilized for immediate use in the surgical theater.
Cyanoacrylate adhesive for surgical closure is a topical-only treatment that eventually sloughs off the top surface of the wound. The product is applied to the surface of the skin to form a glue film that secures apposition of the cut edges of the incision. Currently, the cyanoacrylate is supplied in a device that aids the curing of the adhesive and ensures its safe handling and application.
Several fairly sophisticated delivery systems for new sealant and glue products have been developed or are currently under development. As new procedures are developed for cyanoacrylate and new glues, new devices will be required to aid the procedure. The devices will contribute an increasing proportion of the value associated with the gluing process.
Sophisticated surgical instruments are being developed to facilitate the application in each new indication for new high-strength glue products. High-strength glues are increasingly being utilized to repair vascular joints in coronary bypass operations. Customized instrumentation is designed to hold vessels in place and facilitate the application of exact amounts of adhesive and to avoid subsequent delays from leakage, or imperfect integration of the grafted tissues.
Advanced products for the closure, sealing, hemostasis and other endpoints for medical and surgical wounds generate varying degrees of clinical benefit based on the manner and extent to which they enable management of different wound types. Degrees range from the acute need end of “important and enabling” to the less clinically necessary “aesthetic and perceived benefits”:
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.
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).
Cost-effective and time-saving: Immediate reduction in surgical treatment time and follow-up treatments.
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.
These benefits are clearly different on a clinical specialty-by-specialty basis. The numbers of targeted or prospective procedures also vary considerably by specialty. As a result, wound closure and securement products have the following categorized potential use worldwide:
Source: “Surgical Procedures with Potential for the Use of Hemostats, Sealants, Glues and Adhesion Prevention Products, Worldwide “; Report #S190.
MedMarket Diligence (MMD) has published its 2010 report on the worldwide market for surgical sealants and related products in surgical and traumatic wound management.
The analysis by MMD reveals the size of the evolving opportunity for a diverse set of products in global markets. Based on extensive primary and secondary research, and leveraging MMD’s position as the leading source for the medtech industry on the subject, the report provides industry participants and hopefuls with invaluable data and insights.
This report details the complete range of sealants & glues technologies used in traumatic, surgical and other wound closure, from tapes, sutures and staples to hemostats, fibrin sealants/glues and medical adhesives. The report details current clinical and technology developments in this huge and rapidly growing worldwide market, with data on products in development and on the market; market size and forecast; competitor market shares; competitor profiles; and market opportunity.
This report is a market and technology assessment and forecast of surgical sealants, glues, hemostasis, other wound closure and anti-adhesion. The report details the current and emerging products, technologies and markets involved in wound closure and sealing using sutures and staples, tapes, hemostats, fibrin and sealant products, medical adhesives and products to prevent surgical adhesions. The report provides a worldwide historic (from 2008), current and annual forecast to 2015 of the markets for these technologies, with particular emphasis on the market impact of new technologies through the coming decade. The report provides specific forecasts and shares of the worldwide market by segment for the U.S., Europe (United Kingdom, German, France, Italy, BeNeLux), Latin America, Japan, Korea and Rest of World.
The report provides background data on the surgical, disease and traumatic wound patient populations targeted by current technologies and those under development, and the current clinical practices in the management of these patients, including the dynamics among the various clinical specialties or subspecialties vying for patient population and facilitating or limiting the growth of technologies.
The report establishes the current worldwide market size for major technology segments as a baseline for and projecting growth in the market over a five-year forecast. The report also assesses and projects the composition of the market as technologies gain or lose relative market performance over this period.
See link for complete table of contents and list of exhibits. The report may be ordered for immediate download from link.
The global market for surgical sealants, glues, other wound closure and anti-adhesion products (collectively referred to as "securement "products) is, like many medtech markets, dominated by the U.S., followed by Europe. But as one examines the performance of individual product segments in this market, it becomes clear that local markets have enough differences in their drivers to result in surprising variation from one another.
Below are illustrated the absolute size of the markets for products in securement by country and the relative contribution of revenues from each securement product type by country. The differences stand out.
Source: Preliminary findings, Report #S180, "Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2010-2015". (Publishing October 2010)
Nature-inspired surgical glue. Researchers at Brigham and Women’s Hospital and Boston Children’s Hospital are developing a poly(glycerol sebacate acrylate) (PGSA), a gel-like biomaterial that is composed of glycerol, a common ingredient in pharmaceutical, food and other human use, and sebacic acid, a naturally occurring fatty acid. This biomaterial compound will potentially enable strong, non-toxic adhesion of tissues while being water insoluble, a set of key requirements for effective surgical glues that can function in internal (as opposed to topical) applications. See link.
Oysters. Research is being done by Jonathan Wilkder at Perdue University on the naturally occurring cement used by oysters to secure their shells to each other and to reefs making extensive structures. The “cement” has turned out to be 10% organic (a protein) and 90% inorganic calcium carbonate, which turns out to be only slightly different in proportions than the oysters’ shells. Most importantly, and this is an important consideration in the study, this cement is wet-setting, which is a valuable characteristic of surgical glue or bone cement.
Since manufacturers wish to develop a surgical glue with the requisite strength while also being biocompatible, the bioglues of oysters, mussels and other organisms become acutely of interest. By contrast, synthetically developed high strength glues are often cyanoacrylate-based or similar and are therefore characterized by toxicity in local tissues, limiting their use to topical applications.
Bioglues are a topic of coverage in MedMarket Diligence’s analysis of the global products, technologies and markets surgical sealants, glues and wound closure. See “Worldwide Market for Surgical Sealants, Glues, Wound Closure and Anti-Adhesion, 2012-2017″, Report #S190, publishing February 2012.