Tepha, Inc., a Boston-area medical device company, hopes its newly developed absorbable mesh will provide a solution to this problem. The mesh is made of a novel, naturally produced type of polyester material called TephaFLEX® polymer, also known as poly-4-hydroxybutyrate (P4HB). TephaFLEX Surgical Mesh retains its strength considerably longer than meshes made from traditional synthetic absorbable polymers; studies in animals reveal that TephaFLEX Surgical Mesh retains over half of its original strength after 12 weeks in vivo, while a commonly used synthetic mesh loses virtually all of its strength after only 4 weeks. Thus, mesh made of TephaFLEX provides reinforcement for a period of time more compatible with the tissue repair process. “That’s the key,” says Dr. David Martin, Senior Director of Research and Development at Tepha, “to provide the necessary structural support during the wound healing process without the long-term implications of a permanent implant.”
In addition to overcoming the hurdle of absorption rate, TephaFLEX biopolymer exhibits a number of other advantages. It is more flexible than its synthetic counterparts, making it easier for surgeons to handle, but it is still very tough. The by-product of its degradation (the 4HB monomer) is a natural human metabolite present in a number of organs and tissues, including the brain and the heart. Thus, it is not surprising that TephaFLEX absorption does not appear to have any negative effects in vivo, particularly since there is virtually no accumulation of 4HB due to the slow rate of biopolymer degradation and the rapid elimination of 4HB from the body.
A Microbial Workforce
Although the value of TephaFLEX material stems from its strength and functionality, the process by which the polymer is produced is also remarkable. In nature, some microorganisms make similar polyesters as part of an energy storage scheme when they do not have access to certain nutrients. Because it is impossible to synthesize P4HB chemically in a test tube, large-scale production of the polymer requires exploitation of this natural biological process.
Two decades ago, a group of scientists at Massachusetts Institute of Technology developed a process to do just that. By introducing a handful of genes into a laboratory strain of E. coli and growing the bacteria under specific conditions, they induced the production of P4HB. Vast quantities of the polymer are generated and accumulate as distinct granules in the bacterial cell. The polymer is then extracted and purified as a raw material before it is processed and shaped into its desired form. Unlike many other naturally occurring biopolymers, P4HB is thermoplastic, meaning that it can be softened with heat; this makes it easier to mold TephaFLEX into forms suitable for a range of purposes.
Moving Toward Clinical Application
Tepha has performed a series of in vivo studies to determine the safety and absorption characteristics of TephaFLEX, and has also confirmed the ability of the mesh to support hernia repair in an animal model. Based on these results, Tepha recently received clearance from the Food and Drug Administration to market its Surgical Mesh, as well as TephaFLEX Absorbable Sutures, in the United States. In addition to making two potentially valuable medical device products available for use, this success is significant for another reason. “This is the first biologically derived polyester used in a medical device,” explains Martin.
The next step is commercialization of the mesh and suture product lines. This is not a job the small company plans to undertake on its own. “Tepha is now in the process of identifying distribution partners for the commercialization of TephaFLEX mesh as a hernia repair and general surgery medical device,” explains Dr. Ajay Ahuja, Tepha’s Director of Business Development. Tepha already has commercial relationships for the marketing of the absorbable sutures.
Tepha envisions a number of additional applications for TephaFLEX and other similar naturally produced polymers, and is currently pursuing possibilities in cardiovascular health and orthopedics. Experiments in animal models indicate that TephaFLEX material can serve as a tissue regeneration scaffold for pulmonary artery augmentation and heart valve replacement, providing a matrix to guide growth of a patient’s own cells into a functional tissue before melting away. Tepha is also developing TephaFLEX-based devices for the repair of ligament, tendon, and cartilaginous tissue injury, as well as exploring how best its technology may be harnessed as a platform for controlled drug delivery.
If these biopolymers perform to their potential, Tepha will be well poised to create innovative products as well as improve existing medical devices for a wide range of applications. Success will mean, among other things, that patients will no longer need to worry about the potential complications of carrying a permanent memento of their surgery.
This research is funded in part by the National Institute of Biomedical Imaging and Bioengineering.
Martin DP, Williams SF. Medical applications of poly-4-hydroxybutyrate: a strong flexible absorbable biomaterial. Biochem Eng J. 2003;16:97-105.