Category Archives: surgery

topic is largely or exclusively about surgical products, technologies, markets and/or companies

Product Development in Surgical Glues

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.

Screen Shot 2014-04-23 at 3.49.13 PMDevelopment 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
Screen Shot 2014-04-23 at 3.54.26 PMCollagen 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)
Screen Shot 2014-04-23 at 3.55.52 PMPolymers 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
Screen Shot 2014-04-23 at 3.58.05 PMAlbumin, 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.

Delivery Systems

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Source: CryoLife

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.


Source: MedMarket Diligence, LLC; Report #S190, “Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2010-2017.”

Where will medicine be 20 years from now?

My answer from this question on Quora.

I can answer this question, at least speculatively, from the perspective of clinical practice and medical technology. The other side of “where medicine will be” is the question of healthcare delivery systems, reimbursement, etc. To get that part of it out of the way, 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Most surgical procedures will achieve the ability to be virtually non-invasive. Natural orifice translumenal endoscopic surgery 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.
  • 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.
  • 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.


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.

The Aesthetics & Reconstructive Surgery Products Global Market

Global medical aesthetic products are to achieve sales of more than $6.5 billion in 2013. Through 2018 the market is expected to reach a value of about $10.7 billion. Europe has been witnessing relatively a slower growth of 6.6% per year. Declining purchasing power, particularly in southern Europe affects the European market and this geographical segment is estimated at $1.84 billion in 2013 to reach $1.94 billion in 2018. The U.S. and the Latin America markets will have a CAGR close to 10%. The U.S. and Latin America will experience a growth respectively of 9.2% and 10% in line with global trends. The U.S. market still represents 45% of the global market.

Screen Shot 2014-04-15 at 7.27.04 AMThe Asia/Pacific region will have an overall CAGR of more than 14.1%. Asia will experience the strongest growth through 2018 and exceed the level of the European market in 2018 to $2.24 billion. Overall, the annual growth of the world market between 2013 and 2018 should be 10% to $10.7 billion.

The injectable products (botulinum toxin and fillers mainly hyaluronic acid) constitute the top market segment in value and will have a CAGR of 10.8% until 2018, thus confirming their constant development potential. Since 2012, the toxins market marginally exceeded the dermal fillers market in the world but with a few exceptions such as Europe. The main markets for injectable products by decreasing order are the U.S., E.U., Asia and South America.

The energy-based devices (laser, radiofrequency, ultrasounds) will have an average CAGR of 10.3% until 2018. The sub-segment of body contouring devices will have an average CAGR of 12.1% until 2018. It should represent as nearly half of the activity-based equipment energy by 2018. The main markets for energy-based devices by decreasing order are the U.S., E.U. Asia and South America.

The cosmeceuticals (active cosmetics) will follow the same trend as the injectable products. The major markets for active cosmetics in decreasing order are the U.S., Asia, South America and the E.U. The market for active cosmetics in 2013 and 2018 will be $1,026 million and $1,677 million respectively. The breast implants will have a reduced progression of 5.2% per year until 2018. The major markets for breast implants by decreasing order are the U.S., South America, E.U. and Asia. The 2013 and 2018 market for breast implants will be about $1,066 and $1,370 million respectively. The two most popular cosmetic surgery procedures are still, in the world as well as for each geographical area, the liposuction and the breast augmentation with prosthetic implants. Breast implants experienced a slowdown of about 9% mainly due to concerns about the safety of their components, but this suspicion seems to disappear gradually in recent months.

More limited surgical procedures now are performed in the face, arm, or the internal face of thighs. The goal is primarily to make a change with a natural result. For the face it is readily associated with fat injection to recover volumes. Minimal invasive therapies enjoy a strong growth in 2013, especially with the new botulinum toxin. Alternative techniques to the toxin as cryomodulation begin to develop. The non-invasive techniques are increasingly linked to each other: toxin for the upper face and hyaluronic acid for the lower face, willingly associated with rejuvenation and retightening techniques of the skin by radio frequency and light peels. Far from being opposed to surgery, these techniques maintain surgery result. There is strong growth of surgical cosmetic procedures for men and women above 50 years old in Western countries due to the demand for anti-aging treatment and social pressure. These procedures increased from 28% to 36% between 2005 and 2011, this demand is also significant for invasive treatments and non-invasive.

From “Global Markets for Products and Technologies in Aesthetic and Reconstructive Surgery, 2013-2018″, Report #S710, published by MedMarket Diligence, LLC.

Wound management spans big to small, established to startup

The worldwide wound management market is represented by a mixture of a small group of well established companies like Johnson & Johnson, 3M, KCI, Smith & Nephew, Systagenix and Covidien and a large number of mid-sized and smaller companies with niche product offerings; see Report S249 for a list of profiled companies (and note that we have profiled a select number of active companies discussed in the report).

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Source: MedMarket Diligence, LLC; Report S249.

The fastest-growing market segment is the Growth Factors market, with a compound annual growth rate well in excess of 20% annually since 2012. Favorable clinical evidence is a major driver of that growth. The largest product segment is Traditional Adhesive Dressings, followed by Negative Pressure Wound Therapy. The largely generic adhesive dressing continues to be used for the majority of wound care cases. Negative Pressure Wound Therapy is coming into increasing use as smaller devices allow use in non-hospital settings, and as the technology demonstrates efficacy.

The wound management market is, overall, a mature business sector which contains both long-established product groups and more recently developed approaches to wound care. Price competition remains the key strategy in maintaining value share for the major players. The major components of the market include:

  • Traditional wound care products, such as bandages, dressings and swabs made of generic cotton and textile fabrics.
  • Wound closure devices, including familiar devices such as sutures and staples, as well as newer methods of wound closure such as tissue sealants and glues; also hemostatic devices to help arrest bleeding while closing the wound. Wound closure devices are primarily used in surgery, and are not addressed in this report.
  • Advanced wound care (AWC) products. This umbrella covers dressings which are based on moist wound healing concepts, active therapies such as biomaterial composites and tissue engineered products, and products encompassing aspects of growth factors and angiogenesis. AWC products may be made of biopolymers, hydrocolloids, composites, foam materials, films, etc. These are used mainly for the treatment of chronic and slow-to-heal wounds.
  • Consumer wound care. This sector includes a wide range of wound care products, primarily for use in first aid. The consumer wound care market is not addressed in this report.

A company which develops expertise in engineering and manufacturing in one area of wound management will frequently leverage those skills by expanding into related areas of wound care. For this reason, a number of the leading wound management companies market products within most or all of these categories. When it comes to the advanced wound care products, wound management businesses may choose a strategy of partnering with specialist developers of these novel technologies. Such collaborations often lead to the larger firm acquiring the technology and/or the company that developed the technology, in order to bring the intellectual property in-house, as well as to optimize manufacturing and supply.

Global health care expenditure is expected to grow by at least 6% compound annual growth rate (CAGR) between 2011 and 2020. The demographic changes driving this growth include the aging of the population, the continuing increase in new technologies commanding ever higher prices, and improved understanding of disease processes. This last leads to development of new procedures, products, and therapy regimens to treat disease, which feeds (at least in the USA) into an increasing desire on the part of patients to have the latest and greatest in treatment, no matter the cost to society. Chronic wounds are born out of vascular disease and insufficiency, and diabetic conditions. These are prevalent within the older populations that are showing strongest growth in the developed economies.

Over $24 Billion in Spent on Plastic Surgery Worldwide

And that’s just the product sales including implants, fillers, and other products used for aesthetics and reconstruction. It doesn’t include the physician fees, the outpatient site fees and other money spent.

There are two parts to this, of course. Plastic surgery has two faces — reconstruction and aesthetics, the first medically-indicated and the second elective.  Of course, the surgical reconstruction of anatomy and outward appearance to restore what has been lost to disease or trauma (the medically-indicated side of plastic surgery) has  benefitted greatly by the expertise and medtech innovation of aesthetics (the elective side).  Because of this, the market for products in plastic surgery has elements of both the traditional medtech market (reimbursement, economy-independed funding) and consumer markets (elective products, sensitivity to general economic conditions).

Overall, the market for these products is growing at a compound average of 7.9%, which is a strong but not extraordinarily high growth rate for a medtech market. Within it, of course, there is wide variation in the growth rates of plastic surgery product sales. Below is illustrated the aesthetics and reconstructive surgery products market from 2013 to 2018.

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MedMarket Diligence, LLC; Report #S710

 

Use of Surgical Sealants for Cranial and Spinal Dura

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…

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Source: MedMarket Diligence, LLC; Report #S190

… a different niche use of sealants is stopping cerebrospinal fluid leaks and other dural wound treatments associated with cranial and spinal procedures. These include their use in:

  • Cranial and spinal dural plastic surgery to prevent CSF fistulas.
  • Dural plastic surgery in residual cavities following tumor removal.
  • Dural lacerations in hemilaminectomy operations

Of this, most of the use is currently in cranial applications, but use in spinal applications is growing considerably faster:

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Source: MedMarket Diligence, LLC; Report #S190

 

 

 

The increasing problem of chronic wounds, and their medtech solutions

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.

Worldwide Share of Wound Prevalence By Type, 2011

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Source: MedMarket Diligence, LLC; Report #S190 and Report #S249.

 

Worldwide Share of Wound Prevalence By Type, 2025

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Source: MedMarket Diligence, LLC; Report #S190 and Report #S249.

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.