Thomas Morrow, MD

An absorbable polyester material holds great promise beyond its primary use as a new type of surgical suture

Thomas Morrow, MD

Mention the word "polyester" and most people will immediately think of a 1970s leisure suit, remember a costume party or recall a popular spy parody. But not all polyester is laughable.

The FDA has just approved the first polymer suture material created using recombinant technology, and it is actually a type of absorbable polyester. The product, Tephaflex Absorbable Suture, is made from a specific type of polyester derived from the class of polymers called polyhydroxyalkanoates, or PHAs.

There are numerous polymers, both natural and synthetic, used in medicine. Stedman's Medical Dictionary defines polymer as "a substance of high molecular weight made up of a chain of identical repeated base units." The base unit can be made up of polysaccharides, amino acids, nucleic acids, or any of a number of other organic monomers.

Currently available polymers use specific properties to meet medical needs. Polymers are used to create catheters, contact and implantable lenses, sutures, hemofiltration membranes, surgical glues, vascular grafts, and prostheses. Other polymers are made up of proteins such as collagen, and are used in wound dressings and drug delivery microspheres. Still others are made up of chains of sugars (polysaccharides) such as hyaluronic acid derivatives, and are used for viscosupplementation in patients with degenerative joint diseases.

PHA recombinant polymer

The creation of this PHA recombinant polymer may not appear to be an important development, but the impact of this remarkable material and the process to manufacture it is likely to be immense because of its potential use in heart valve replacement and organ, tendon, and ligament harvesting.

PHAs are naturally occurring compounds created by a large number of both gram positive and gram negative bacteria. By polymerizing small soluble organic molecules into large macromolecules, the cell can store significant amounts of energy in an insoluble form that does not alter its osmotic state and that is not lost to the local environment.

Once extracted from the cell, these molecules exhibit properties very similar to common plastics such as polypropylene.

Literally thousands of potential PHAs can be created by a variety of bacteria. The type and characteristics of the PHA can be "fine tuned" by scientists by regulating a number of variables including gene makeup, environment, blend of nutrients, and pH. The genes used for this technology were discovered and isolated in the 1980s. Numerous genes encoding enzymes involved in the creation of PHAs in the bacteria have since been cloned and have led to recombinant varieties of bacteria specifically tailored to the needs of specific medical applications.

Poly-4-hydroxybutyrate

Tephaflex Absorbable Suture is the first absorbable polymer suture made from material isolated from bacteria that have been modified using recombinant DNA technology and tailored to meet specific needs for a biopolymer.

The material used to manufacture the suture is poly-4-hydroxybutyrate. This polymer cannot be produced via chemical synthesis. It is grown through fermentation using recombinant E. coli. Native E. coli cannot produce biosynthetic polyesters without the addition of the proper gene, hence the need for recombinant technology.

Precise production is possible by implanting the gene in this well-studied bacterium. Tephaflex material is purified from the bacteria after lysing the cell membranes. Particular attention is paid to removing endotoxin, a naturally occurring toxin in bacteria.

Remarkable properties

This molecule has remarkable properties. First, it contains none of the residual metal catalysts that are used in making synthetic polyesters. It is superior in strength and more flexible than synthetic absorbable monofilament sutures currently marketed in the United States. Its breaking point is roughly 10 times its original length. It has a long shelf life, having greater resistance to degradation by moisture than other absorbable polymers, and it is easy to sterilize using ethylene oxide, a common medical sterilization agent. It acts like other plastics in that it "melts" at reasonable temperatures and can be molded and extruded into a variety of shapes. It also can be "poured" into a variety of shapes and will "fill" irregular surfaces.

The Tephaflex material breaks down in a manner that results in a gradual loss of tensile strength, with no significant inflammatory reaction. As it degrades, it yields small amounts of a non-toxic natural human metabolite — 4-hydroxybutyrate (4HB), which in turn is metabolized in the Krebs cycle, yielding carbon dioxide and water.

The material would not be much of a breakthrough if the only commercial application were an improved suture.

This and similar materials are being studied for use in peripheral nerve repair "guides," absorbable coronary and peripheral stents and stent coatings, vascular grafts, film products, and surgical meshes and patches for cardiovascular, ligament, tendon, and cartilage repair — as well as in drug delivery applications.

Valvular heart disease

Even more exciting is the potential for use of this material in valvular heart disease. Nearly 100,000 heart valve replacements are performed in the United States each year for both congenital and acquired disorders. Currently available valves are either mechanical or porcine in origin, but are deficient in a number of ways.

For example, the current valves do not grow as the patient grows, so children who undergo this type of heart valve replacement must undergo additional surgery on a periodic basis. In addition, surgeons need an improved "patch" material that can serve as a tissue scaffold for repair of heart defects rather than the nonviable material currently used.

Some constructs made of Tephaflex material seal themselves after a suture. Currently available materials "leak" through needle holes.

In studies conducted on sheep, scientists created a heart valve using Tephaflex material as part of an absorbable scaffold. After seeding this scaffold with vascular cells, the matrix was grown in a dynamic flow chamber that simulated the heart. As the vascular cells proliferated over time, sufficient "living" material was created and was readied for implantation. This tissue-engineered heart valve functioned well, without thrombus formation or stenosis. After 20 weeks, the implanted material was almost indistinguishable from the native valve in tensile and mechanical properties, biochemical analysis, and function. Interestingly, the histological structure took on the characteristic three distinct organized layers of a native valve and it appeared to grow in size with the growth of the lamb.

Although only the suture material is currently available, this remarkable substance could signal the start of a new revolution in the biotechnology field that will unfold for those who seek Tomorrow's Medicine.

Thomas Morrow, MD, is the immediate past president of the National Association of Managed Care Physicians. He has 21 years of managed care experience at the payer or health plan level.
Dr. Morrow is employed by Genentech, Inc., as a director in the value-based health department. During the last three years, before taking the Genentech position, he received honoraria or other financial benefits from: Amgen, Amylin Pharmaceuticals, AstraZeneca, Biogen Idec, Centocor, Galderma, GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Novo Nordisk, Pfizer, Procter & Gamble, Q-Med, Sanofi-Aventis, Teva Pharmaceuticals Industries, UCB, and Wyeth. The views expressed in Tomorrow's Medicine are Dr. Morrow's alone.

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