Add tick cement to the list of natural adhesives pursued for medical applications

In past posts, we have reported on multiple naturally-occurring substances or methods for strong adhesion that are being investigated for their potential to be exploited for medical or surgical adhesion. These include adhesives from remora, mussels, geckos, crab shells, barnacles, Australian burrowing frogs, spider webs, porcupine quills, sandcastle worms, etc.

Researchers from MedUni Vienna and Vienna University of Technology are now investigating 300 different ticks for the “cement” used by the parasites to attach to hosts. The goal is to study the composition of the natural tick “dowel” used by the mouthparts of ticks and determine how it might serve as a template for new tissue adhesives.

The Vienna research also notes other natural adhesives are similarly being investigated for medical and surgical use:

Other potential “adhesive donors” are sea cucumbers, which shoot sticky threads out of their sac; species of salamander, which secrete extremely fast-drying adhesive out of skin glands, if attacked; or insect larvae, which produce tentacles or crabs, which can remain firmly “stuck,” even under water.

The incentive for studying natural adhesives is that they have been driven by evolution to provide strong adhesion without toxicity in various wet or dry conditions that are challenging for existing synthetic or existing natural glues (e.g., fibrin glues, cyanoacrylates, etc.). Surgical glues currently in use have some limitation arising from lesser strength, ease of use, toxicity, and other shortcomings. New glues will gain wider adoption, capturing procedure volume used with sutures, clips and other closure methods, particularly in internal use, if they are stronger and/or provide tighter seals (without needing to be combined with sutures on the same incision/wound) and do not cause the toxicity that some high strength medical glues do (e.g., synthetics like cyanoacrylates; “super glues”). The biologically-derived glues (or the surfaces structures of gecko feet) avoid the toxicities of synthetics and have often proven to have very high tensile strength. (The fast-curing cement used by barnacles has been shown to have a remarkable tensile strength of 5,000 pounds per square inch.)

Edit: See also, Biomimetic Glue, based on shellfish natural adhesive.

MedMarket Diligence tracks the technologies, clinical practices, companies, and markets associated with medical and surgical sealants and glues, with the most recent coverage in, “Worldwide Markets for Medical and Surgical Sealants, Glues, and Hemostats, 2015-2022,” (report #S290).

Six Key Trends in Sealants, Glues, Hemostats Markets to 2022

From July 2016 published Report #S290.

Here are six key trends we see in the global market for surgical sealants, glues, and hemostats:

  1. Aggressive development of products (including by universities, startups, established competitors), regulatory approvals, and new product introductions continues in the U.S., Europe, and Asia/Pacific (mostly Japan, Korea) to satisfy the growing volume of surgical procedures globally.
  2. Rapid adoption of sealants, glues, hemostats in China will drive much of the global market for these products, but other nations in the region are also big consumers, with more of the potential caseload already tapped than the rising economic China giant. Japan is a big developer and user of wound product consumer. Per capital demand is also higher in some countries like Japan.
  3. Flattening markets in the U.S. and Europe (where home-based manufacturers are looking more at emerging markets), with Europe in particular focused intently on lowering healthcare costs.
  4. The M&A, and deal-making that has taken place over the past few years (Bristol-Myers Squibb, The Medicines Company, Cohera Medical, Medafor, CR Bard, Tenaxis, Mallinckrodt, Xcede Technologies, etc.) will continue as market penetration turns to consolidation.
  5. Growing development on two fronts: (1) clinical specialty and/or application specific product formulation, and (2) all purpose products that provide faster sealing, hemostasis, or closure for general wound applications for internal and external use.
  6. Bioglues already hold the lead in global medical glue sales, and more are being developed, but there are also numerous biologically-inspired, though not -derived, glues in the starting blocks that will displace bioglue shares. Nanotech also has its tiny fingers in this pie, as well.

See Report #S290, “Worldwide Sealants, Glues, and Hemostats Markets, 2015-2022”.

The Demand for Sealants, Glues, and Hemostats in 2016

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

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


Source: MedMarket Diligence, LLC; Report #S290.

Medical Sealants

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

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

Hemostatic Products

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

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

Medical Glues

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

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


Opportunities for med/surg sealants, glues, hemostats driven by type of clinical benefit, competition

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.

High Strength Medical and Surgical Glues

See the updated, published 2012 Report #S190, “Surgical Sealants, Glues, Sutures, Other Wound Closure and Anti-Adhesion, Worldwide Markets, 2012-2017.”

Cyanoacrylate products are the main form of high-strength surgical glue that is approved for human clinical use in the worldwide market. A number of new materials are under development for internal use in particular, but these represent new chemical entities and their commercialization is likely to be delayed by regulatory requirements.  While sutures will be replaced by cyanoacrylate glues in many procedures over the next 10 years, this will only occur after some technical challenges are overcome. For example, cyanoacrylate glues used for external skin closure are approximately five times less strong than sutures, and cyanoacrylates produce cytotoxic compounds as part of the curing process when used for securing torn or excised tissue. This has delayed the development and clinical evaluation of these potentially useful materials for internal surgical procedures. However, cyanoacrylate glues are marketed actively by a number of companies for topical wound closure in accident/emergency situations and in surgical closure.

Given the current size of the global market for high strength glues (at over $700 million) and the potential for this market to expand as products overcome the challenges of strength and toxicity, a respectable number of competitors compete in this space and many are working on further developing cyanoacrylate-based and other high strength adhesives (including fibrin-based and other “bio-glues”) to not only garner greater share of the existing market but to also erode the market for sutures and other mechanical wound closure products (e.g., clips and staples).

Source: MedMarket Diligence Report #S180, “Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2010-2015.”

Ethicon (J&J), Covidien and B. Braun (Aesculap) hold the major positions in the market for high strength medical and surgical adhesives, but their positions are at risk, and will continue to be at risk, as long as the unmet need exists for stronger, more compatible glues.  Some of the many products on the market and in development in the area of high strength glues include SurgiSeal, DermaSeal, FloraGuard, LiquiBand, SkinLink, Histoacryl, Gluetiss, Autologous biological glue, Chemence USP Class VI adhesives, TissueGlu, Indermil, Glubran2, Glubran Tiss, GluSeal, GluSite, PeriAcryl, GluShield, Dermabond, InteguSeal, Epiglu, Surgical Tissue Sealants (STS) and others.

Technology platforms and clinical applications overlap

Diverse technologies have a surprising number of common threads, whether in the technologies themselves or in the clinical applications.  For this reason, manufacturers need to consider that:

1. A technology platform can be the launchpad for products in clinically diverse areas. Case in point, cell therapy, which as a fundamental scientific discipline can have uses as far afield as wound management, bone repair, treatment of myocardial ischemia and others.

2. A disease state can sometimes be targeted by many very different technologies.  Examples include that wound management can be accomplished by tissue engineering, sutures, fibrin-based surgical glues, cyanoacrylate-based surgical glues, dressings and others.

The driver behind technologies having multiple clinical applications is, of course, that companies wish to maximize their ROI.  

The driver behind single disease states being the target of multiple alternative technologies is cost — healthcare systems (in principle, anyway) seek the most competitive options for treating specific patient populations, and this driver has been gaining momentum over the past ten years due to “managed care” efforts as well as aggressive, cost-focus innovators creating technologies that displace market share with convincingly better patient outcomes compared to alternative technologies.

MedMarket Diligence publishes medical technology market reports on a wide range of clinical and technology subjects (of course, sometimes overlapping). See list.

(This post was done via the Palm Pre WebOS app Po’ster by Gabriele Nizzoli.) 

Sandcastle worms, mussels, burrowing frogs and gecko feet

Add to the list of naturally occurring glue sources — mussels, the C. crescentus bacteria, Australian burrowing frogs and the gecko ("geckel" glue) — the sandcastle worm.  University of Utah bioengineers have made a synthetic version of a superglue based on a naturally occurring glue produced by sandcastle worms, which use this glue to build tube shaped homes out of bits of sand and shell fragments.

The synthetic version of the sandcastle worm glue is being explored for its application in orthopedic applications — glueing together small bone fragments in fractured knees, wrists, elbows, and ankles, as well as the face and skull.  The applications will at least initially not be for gluing load-bearing sites like large bone fractures, since these can be addressed with screws and pins, while small fractures are more problematic for existing methods.

The researchers will be publishing their findings in the journal Macromolecular Biosciences.

Naturally occurring glues, especially those such as the above, which have demonstrated high strength, are particularly of interest for medical/surgical applications, since existing "biocompatible" glues such as autologous fibrin sealants provide reasonably effective sealing, and even hemostasis, but do not withstand the more challenging stresses of orthopedics and other applications like sealing leaks in lung resections.  The higher-strength alternative to fibrin sealants is cyanoacrylate-based glues, but for all their "superglue" strength, their toxicity is a limiting factor.  It is for this reason that naturally occurring "bioglues" like those from mussels, geckos and sandcastle worms hold such promise.

MedMarket Diligence published its report #S175, "Worldwide Surgical Sealants, Glues and Wound Closure Market, 2009-2013" for publication in January 2009.