The modern world would fall apart without glue. It is critical to the manufacturing of all kinds of items we depend on in our daily lives, from shoes to shelves to the roof over our heads. High-tech adhesives hold together airplanes and keep boats afloat. And humanity has been depending on sticky stuff for a long time. The earliest evidence of the use of glue dates back 200,000 years, when birch bark pitch was used to hold stone flakes to a crude wooden spear.
Adhesive materials are also common and incredibly useful in health care. Where would we be without the humble Band-Aid? Surgeons use a variety of glues and cements to stop bleeding, bind artificial joints, and close lacerations.
Now we have the first synthetic adhesive for internal soft tissue use, Cohera Medical’s TissuGlu Surgical Adhesive. Approved by the FDA in February as a medical device, TissuGlu is indicated for “the approximation of tissue layers where subcutaneous dead space exists between the tissue planes in abdominoplasty.”
Abdominoplasties—more commonly known as tummy tucks—remove excess skin and fat from the abdomen and, in most cases, involve some restoration of the muscles of the abdomen. They are done to remove hanging skin after someone has lost a great deal of weight as well as for cosmetic purposes. An abdominoplasty requires a lot of dissection, which, in turn, creates a space where fluid can pool and create seromas, pockets of serous fluid.
Seromas can delay healing, and they are a fertile place for bacteria to grow and produce a harmful infection. Typically, surgeons use numerous sutures between the tissue layers to tie the outer tissue to the muscle layer in a process similar to the process used to make quilts.
In addition, as an extra precaution, they often place tubes into the area to allow the fluid to drain, and sometimes a suction device is attached to these drains to pull any extra fluid out. When fluid isn’t allowed to gather, the tissue layers stay in contact with one another so they forge a nice strong bond during the healing process.
TissuGlu, a biocompatible polyurethane based prepolymer, creates a strong bond between tissue planes in the presence of moisture. The wound surfaces provide the moisture, so it does not need to be premixed. The adhesive is applied in drops to the tissue surface with an applicator that looks like what it is: a very precise, high-tech glue gun. The head of the applicator has a spacer guide, so the surgeon can deliver the tissue glue in grid with each drop 2.5 centimeters apart.
The adhesive takes between 30 and 45 minutes to cure, and the curing takes place while the surgeon and his team are busy with other tasks to complete the surgery. The adhesive’s bond is designed to stay strong enough to allow for complete healing and then, over time, degrade so the chemical components are eliminated from the body.
TissuGlu underwent numerous biocompatibility tests for cytotoxicity, pyrogenicity, carcinogenicity, reproductive toxicity, and other harms. The adhesive was studied in two pivotal trials. The first was conducted to evaluate safety and determine whether TissuGlu plus the use of drains was superior to the use of sutures plus the use of drains. This study failed to demonstrate superiority but did demonstrate safety.
The second study was also designed to evaluate safety and adverse events but, more importantly, to evaluate whether TissueGlu, along with standard wound closure (SWC) techniques but no drain placement, is as safe and effective as SWC with drains. The endpoints included fluid management, seroma formation, subjective satisfaction, and quality of life.
Powered as a noninferiority study, 130 subjects were randomized on a 1:1 basis. The control group received SWC plus the placement of two size 12 Blake drains over the abdominal fascia, delivered through stab incisions to the pubic area that were then fixed with suture. The exclusion criteria were factors that inhibit normal healing, such as a current smoking habit, collagen vascular disease, diabetes, and concurrent use of systemic steroids or immunosuppressive agents. Almost all (98.4%) of the study volunteers were women, most (70%) were white, their median age was 42, and their median weight, 143 pounds. All had skin laxity on the abdomen.
|Primary endpoint results of pivotal TissuGlu trial*|
|Standard wound closing with TissuGlu and no placement of drains (n=66)||Standard wound closing with drains (n=64)|
|Removal of drains||7||128|
*Post-operative invasive treatments include removal of drains, needle aspirations, repositioning of drains, re-insertion of drains.
Source: Cohera Medical
Patient-reported outcomes, collected as descriptive with no formal hypothesis testing, demonstrated that a subset of people in the TissuGlu group were able to shower, walk up stairs, and return to work earlier than their counterparts with the drains.
The primary endpoint of the trial was post-operative treatments, including removal of drains and needle aspirations (see table). The TissuGlu group had fewer postoperative treatments than the control group because there were no drains to remove. As expected, though, the patients in the TissuGlu group experienced more seromas and had more needle aspirations. Seromas that required an operative drain placement were considered serious adverse events, and four of those occurred (two in one patient) as well as one hematoma. A subset analysis based on BMI resulted in a warning that patients with a BMI of over 28 may be at increased risk of seroma complications.
TissuGlu is fascinating. The use of this substance is an attractive alternative to quilting and drain insertion for abdominoplasty. Once surgeons become adept at using the adhesive and the applicator, the operations should take less time. Shorter operations mean less anesthesia for patients and reduced operating room time for surgical teams. By eliminating the puncture wounds required for drain placement, TissuGlu should make the recovery from tummy tucks much more comfortable. A small percentage of TissuGlu patients did end up needing drains, but the majority (73% in the pivotal trial) avoided fluid-related related treatment.
Although the only approved indication for TissuGlu is abdominoplasty, numerous other procedures require the placement of drains so surgeons will look for other uses.
TissuGlu is not a huge leap forward, but it demonstrates that even incremental improvements are important and that any standard medical practice is subject to disruption by Tomorrow’s Medicine!