From 2010 to present (Oct 2015), as included in the Medtech Startups Database, MedMarket Diligence identified 442 new (under one year old) medical technology startups whose businesses encompass, alone or in combination, medical devices, diagnostics, biomaterials, and the subset of both biotech and pharma that is in direct competition with medical devices, including tissue engineering and cell therapy. Of these, 74% were founded in the U.S., 5% were founded in Israel, and the rest were founded in 18 other countries.
Companies in the database have been categorized by clinical and/or technology area of focus, with multiple categories possible (e.g., minimally invasive and orthomusculoskeletal and surgery). Below is the composition of the companies identified from Jan. 2010 to Oct. 2015.
See the 2016 published report #S290, “Worldwide Surgical Sealants, Glues, Hemostats, 2016-2022”.
Tourniquet, pressure and sutures have been used for controlling excessive bleeding during surgical procedures for many hundreds of years. Fibrin sealants represented a revolution in local hemostatic measures for both bleeding and nonbleeding disorders. Fibrin sealant has the potential to provide life-saving control of excessive bleeding in many critical surgical operations and during a number of elective procedures. The terms “sealant” and “glue” are frequently used interchangeably in the surgical context, but there is actually a difference in adhesive strength between sealants, pioneered by fibrin products (sometimes homemade) and the later, stronger glues of which cyanoacrylate-based products are the most common.
In order for a sealant to be effective, the product should meet several parameters, depending upon the application. Among these are:
Ability to close the wound
Strength of bond
Speed of curing
Protection of the wound from infection
Low surface friction
Breathability in order to aid healing
Lack of adverse side effects to skin and internal tissues
Ease of handling
Fibrin and other sealant products have been approved and used outside the United States for many years and their use has created strong awareness of their surgical and economic benefits in Europe, Latin America and Asia. As a result, many such products have been marketed in these regions for 20 years or more, and have been developed for a variety of surgical uses. In the U.S., these products were initially approved as hemostatic adjuncts to suturing. They are increasingly being used for sealing of tissues, but their use beyond simple hemostasis (i.e., as sealants and low-strength glues) lags that of markets outside the U.S.
Despite the development of novel sutures (e.g., resorbable), endoscopically applied clips and other innovations, fibrin sealants will remain a versatile option available to surgeons to achieve hemostasis and sealing of wounds (alone or adjunctively with sutures/staples). Their clinical track record, biocompatibility and ready availability match high demand. Their limitation in adhesive strength, however, does put some limit on their sales potential, since significant demand exists for tight sealing and strong bonding of tissues under stress, such as in lung and bowel resections, cardiovascular and other anastomoses and adhesion of muscle, that go beyond what fibrin sealants can achieve. For this reason, other naturally-occuring “bioglues” are under development that will achieve tighter tissue bonds than fibrin sealants, but without the toxic effects of cyanoacrylates (“superglues”).
There are more than 30 companies worldwide developing fibrin sealants and driving a market that will exceed $2.2 billion by 2017.
In a forthcoming report on advanced technologies associated with the acute phase of wound management — specifically, hemostasis, closure and sealing — MedMarket Diligence will be revealing the state of the art and the industry for fibrin and other surgical sealants; cyanoacrylate and other synthetic and naturally-occurring high strength glues; a wide range of products providing hemostasis; products that prevent the formation of post-surgical adhesions; and the increasingly varied types of physical wound closure, including sutures, staples, clips, tapes, and other mechanical wound closure types.
Our analysis in 2012 illustrated the scope and depth to which these advanced wound closure products had penetrated the realm of many areas of clinical practice that, up to a scan decade ago, had been dominated for a millennia by simple physical methods to manage acute wounds — sutures and tapes. Below is an illustration of the size and growth in e sales of these products, showing that the advanced products are being adopted at accelerated rates, yet a sizable volume of wound closure remains in the hands of very traditional closure (sutures/staples).
Size and Growth of Surgical Securement Product Segments Worldwide 2010-2019
Of course, the field of sutures and staples is not exactly stagnant, devoid of innovation. Sutures, staples and clips innovation have been driven by the commensurate innovation in surgical technique. Traditional surgery via laparotomy has long since been revolutionized by laparoscopy, and endoscopic procedures in general have become the standard for minimizing surgical trauma and faster recovery. The endoscopic format has demanded new suturing and stapling technologies, and industry stalwarts like Ethicon, Covidien and others have been happy to provide the solutions. And even more recently, natural orifice transluminal endoscopic surgery (NOTES) procedures are pushing the minimally invasive principle to a greater extreme.
(This question was originally posed to me on Quora.com. I initially answered this in mid 2014 and am revisiting and updating the answers now, in mid 2015.)
An important determinant of “where medicine will be” in 2035 is the set of dynamics and forces behind healthcare delivery systems, including primarily the payment method, especially regarding reimbursement. It is clear that some form of reform in healthcare will result in a consolidation of the infrastructure paying for and managing patient populations. The infrastructure is bloated and expensive, unnecessarily adding to costs that neither the federal government nor individuals can sustain. This is not to say that I predict movement to a single payer system — that is just one perceived solution to the problem. There are far too many costs in healthcare that offer no benefits in terms of quality; indeed, such costs are a true impediment to quality. Funds that go to infrastructure (insurance companies and other intermediaries) and the demands they put on healthcare delivery work directly against quality of care. So, whether it is Obamacare, a single payer system, state administered healthcare (exchanges) or some other as-yet-unidentified form, there will be change in how healthcare is delivered from a cost/management perspective.
From the clinical practice and technology side, there will be enormous changes to healthcare. Here are examples of what I see from tracking trends in clinical practice and medical technology development:
Cancer 5 year survival rates will, for many cancers, be well over 90%. Cancer will largely be transformed in most cases to chronic disease that can be effectively managed by surgery, immunology, chemotherapy and other interventions. [View Aug. 2015: Cancer has been a tenacious foe, and remains one we will be fighting for a long time, but the fight will have changed from virtually incapacitating the patient to following protocols that keep cancer in check, if not cure/prevent it.]
Diabetes Type 1 (juvenile onset) will be managed in most patients by an “artificial pancreas”, a closed loop glucometer and insulin pump that will self-regulate blood glucose levels. OR, stem cell or other cell therapies may well achieve success in restoring normal insulin production and glucose metabolism in Type 1 patients. The odds are better that a practical, affordable artificial pancreas will developed than stem or other cell therapy, but both technologies are moving aggressively and will gain dramatic successes within 20 years. [View Aug. 2015: Developments in the field of the “artificial pancreas” have recently gathered considerable pace, such that, by 2035, type 1 blood glucose management may be no more onerous than a house thermostat due to the sophistication and ease-of-use made possible with the closed loop, biofeedback capabilities of the integrated glucometer, insulin pump and the algorithms that drive it, but that will not be the end of the development of better options for type 1 diabetics. Cell therapy for type 1 diabetes, which may be readily achieved by one or more of a wide variety of cellular approaches and product forms (including cell/device hybrids) may well have progressed by 2035 to become another viable alternative for type 1 diabetics.]
Diabetes Type 2 (adult onset) will be a significant problem governed by different dynamics than Type 1. A large body of evidence will exist that shows dramatically reduced incidence of Type 2 associated with obesity management (gastric bypass, satiety drugs, etc.) that will mitigate the growing prevalence of Type 2, but research into pharmacologic or other therapies may at best achieve only modest advances. The problem will reside in the complexity of different Type 2 manifestation, the late onset of the condition in patients who are resistant to the necessary changes in lifestyle and the global epidemic that will challenge dissemination of new technologies and clinical practices to third world populations. [View Aug. 2015: Despite increasing levels of attention being raised to the burden of type 2 worldwide, including all its sequellae (vascular, retinal, kidney and other diseases), the pace of growth globally in type 2 is still such that it will represent a problem and target for pharma, biotech, medical device, and other disciplines.]
Cell therapy and tissue engineering will offer an enormous number of solutions for conditions currently treated inadequately, if at all. Below is an illustration of the range of applications currently available or in development, a list that will expand (along with successes in each) over the next 20 years.
[View Aug. 2015: Cell therapy will have deeply penetrated virtually every medical specialty by 2035. Most advanced will be those that target less complex tissues: bone, muscle, skin, and select internal organ tissues (e.g., bioengineered bladder, others). However, development will have also followed the money. Currently, development and use of conventional technologies in areas like cardiology, vascular, and neurology entails high expenditure that creates enormous investment incentive that will drive steady development of cell therapy and tissue engineering over the next 20 years, with the goal of better, long-term and/or less costly solutions.]
Gene therapy will be an option for a majority of genetically-based diseases (especially inherited diseases) and will offer clinical options for non-inherited conditions. Advances in the analysis of inheritance and expression of genes will also enable advanced interventions to either ameliorate or actually preempt the onset of genetic disease. [View Aug. 2015: It’s a double-edged sword with the human genome. As the human blueprint, It is the potential mother lode for the future of medicine, but it remains a complex set of plans to elucidate and exploit for the development of therapies. While genetically-based diseases may readily be addressed by gene therapies in 2035, the host of other diseases that do not have obvious genetic components will resist giving up easy gene therapy solutions. Then again, within 20 years a number of reasonable advances in understanding and intervention could open the gate to widespread “gene therapy” (in some sense) for a breadth of diseases and conditions.]
Drug development will be dramatically more sophisticated, reducing the development time and cost while resulting in drugs that are far more clinically effective (and less prone to side effects). This arises from drug candidates being evaluated via distributed processing systems (or quantum computer systems) that can predict efficacy and side effect without need of expensive and exhaustive animal or human testing. [View Aug. 2015: The development of effective drugs will have been accelerated by both modeling systems and increases in our understanding of disease and trauma. It may not as readily follow that the costs will be reduced, something that may only happen as a result of policy decisions.]
Most surgical procedures will achieve the ability to be virtually non-invasive. Natural orifice transluminal endoscopic surgery (NOTES) will enable highly sophisticated surgery without ever making an abdominal or other (external) incision. Technologies like “gamma knife” and similar will have the ability to destroy tumors or ablate pathological tissue via completely external, energy-based systems. [View Aug. 2015: By 2035, technologies such as these will have measurably reduced inpatient stays, on a per capita basis, since a significant reason for overnight stays is the trauma requiring recovery, and eliminating trauma is a major goal and advantage of the NOTES technology platform. A wide range of technologies across multiple categories (device, biotech, pharma) will also have emerged and succeeded in the market by producing therapeutic benefit without collateral damage.]
Information technology will radically improve patient management. Very sophisticated electronic patient records will dramatically improve patient care via reduction of contraindications, predictive systems to proactively manage disease and disease risk, and greatly improve the decision-making of physicians tasked with diagnosing and treating patients. [View Aug. 2015: There are few technical hurdles to the advancement of information technology in medicine, but even in 2035, infotech is very likely to still be facing real hurdles in its use as a result of the reluctance in healthcare to give up legacy systems and the inertia against change, despite the benefits.]
Systems biology will underlie the biology of most future medical advances in the next 20 years. Systems biology is a discipline focused on an integrated understanding of cell biology, physiology, genetics, chemistry, and a wide range of other individual medical and scientific disciplines. It represents an implicit recognition of an organism as an embodiment of multiple, interdependent organ systems and its processes, such that both pathology and wellness are understood from the perspective of the sum total of both the problem and the impact of possible solutions. [View Aug. 2015: This orientation will be intrinsic to the development of medical technologies, and will increasingly be represented by clinical trials that throw a much wider and longer-term net around relevant data, staff expertise encompassing more medical/scientific disciplines, and unforeseen solutions that present themselves as a result of this approach.]
There will be many more unforeseen medical advances achieved within 20 years, many arising from research that may not even be imagined yet. However, the above advances are based on actual research and/or the advances that have already arisen from that research.
(See the 2016 published report #S290, “Sealants, Glues, Hemostats, 2016-2022”.)
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.
Development Timelines 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.
Surgical sealants have an enormous range of applications in the treatment of acute and chronic wounds, but while the majority of sealant revenues derives from their use in the hemostasis, closure and sealant of tissues to prevent blood loss…
Wounds have many different sources, etiologies and forms and, therefore, demand a range of approaches. By virtue of these differences, they have considerably different costs. At the top of the list of wound culprits driving up cost is the category of chronic wounds. Simply put, these wounds are very slow to heal due to poor circulation at the site (e.g., decubitus stasis, or pressure, ulcers), concomitant health issues (diabetes) and the difficulty in changing the local environment toward one with conditions more conducive to the healing process.
Chronic wounds are not the most common — that is a category represented by surgical wounds, in which the wound has been created medically or surgically in order to excise or otherwise manage diseased tissue. But surgical wounds, traumatic wounds and lacerations are by their nature acute and, especially for surgical wounds, can be surgically managed to create clean wound edges, good vascularization and other conditions that accelerate healing. Therefore, while the volume of surgical and traumatic wounds and lacerations is significant, their costs are manageable and their growth is unremarkable.
But the costs of chronic wounds are higher due to both the types of different products required and the length of time required for those products to be used. Moreover, given the association of chronic wounds with conditions that are growing in prevalence due to increasing incidence of obesity, diabetes and other conditions, combined with an aging population that is increasingly sedentary, the prevalence of chronic wounds is shifting the balance among wound types. Below is the balance of wound types by prevalence worldwide in 2011, followed by the projected balance of wound types in 2025.
Surgical wounds offer the potential for use of devices which can ensure hemostasis, prevent internal adhesions and anastomoses, secure soft tissue, and close the skin. Traumatic wounds also offer potential for skin closure products and for hemostats, and adhesion prevention during post-trauma surgery. New wound-covering sealant products may also offer potential for treatment of cuts, grazes, and burns.
Chronic wounds are generally not amenable to treatment by adhesives, sealants and hemostats unless the wound has either been debrided to a sterile bleeding surface (in which case it becomes like a surgical wound), or the product offers some stimulant activity. Many hemostats exhibit some inflammatory and cytokinetic activity, which has been associated with accelerated healing. However, this inflammatory activity has also been known to burn the patient’s skin. Chronic wounds are instead dealt with often by a combination of debridement, frequent dressing changes, products to address local vascular circulation and pressure (negative and positive) and others. Progress is being made in reducing the associated healing times, but a large opportunity remains.
(See the related 2016 published report #S290, “Sealants, Glues, Hemostats, 2016-2022”.)
Products that provide hemostasis, closure, sealing and anti-adhesion of wounds comprised long established products (e.g., tapes, sutures, etc.) as well as a variety of advanced products such as fibrin and other surgical sealants, surgical glues, hemostats and products to prevent post-surgical adhesion. While traditional products are being innovated to keep pace with advanced products (for example, through the development of absorbable sutures), the shift of caseload and product sales away from traditional products appears unrelenting.
As a result, the balance of the competitive landscape is forecast to shift over the next few years toward advanced sealing, hemostasis, closure and anti-adhesion products. Below is illustrated, in a combined “donut” chart, this shift from 2012 to 2017 in the share of the global market for these products.
These percentage shifts may not seem significant unless one considers that the global market for these products is well over $14 billion.
The MedMarket Diligence Report #S190, “Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2012-2017”, details the complete range of sealants & glues technologies used in traumatic, surgical and other wound closure, including tapes, sutures/staples/mechanical closure, hemostats, fibrin sealants/glues and medical adhesives and anti-adhesion products. The report details current clinical and technology developments, with data on products in development (detailing market status) and on the market; market size and forecast; competitor market shares; competitor profiles; and market opportunity. The report provides full year actual data from 2011. The report provides a worldwide forecast to 2017 of the markets for these technologies, with emphasis on the market impact of new technologies through the forecast period. The report provides specific forecasts and shares of the worldwide market by segment for Americas (detail for U.S., Rest of North America and Latin America), Europe (detail for United Kingdom, German, France, Italy, Spain, Rest of Europe), Asia/Pacific (detail for Japan, Korea, Rest of Asia/Pacific) 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 establish the current worldwide market size for major technology segments as a baseline for and projecting growth in the market through 2017. The report assesses and projects the composition of the market as technologies gain or lose relative market performance over this period. The report profiles 122 active companies in this industry, providing data on their current products, current market position and products under development.
This report details the complete range of sealants & glues technologies used in traumatic, surgical and other wound closure, including tapes, sutures/staples/mechanical closure, hemostats, fibrin sealants/glues and medical adhesives and anti-adhesion products. The report details current clinical and technology developments, with data on products in development (detailing market status) and on the market; market size and forecast; competitor market shares; competitor profiles; and market opportunity. The report provides full year actual data from 2011. The report provides a worldwide forecast to 2017 of the markets for these technologies, with emphasis on the market impact of new technologies through the forecast period. The report provides specific forecasts and shares of the worldwide market by segment for Americas (detail for U.S., Rest of North America and Latin America), Europe (detail for United Kingdom, German, France, Italy, Spain, Rest of Europe), Asia/Pacific (detail for Japan, Korea, Rest of Asia/Pacific) 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 establish the current worldwide market size for major technology segments as a baseline for and projecting growth in the market through 2017. The report assesses and projects the composition of the market as technologies gain or lose relative market performance over this period. The report profiles 122 active companies in this industry, providing data on their current products, current market position and products under development.