Since the first marketed synthetic absorbable suture in the 1960s, absorbable medical materials have developed into a burgeoning industry. By reducing the need for surgical removal procedures and the permanence of implants, absorbable polymers (also known as resorbable or biodegradable polymers) present an attractive option for both patients and medical professionals. Due to compositions featuring a hydrolytically cleavable backbone, these polymers degrade in the presence of moisture, resulting in physical dissolution when in contact with bodily tissues. By altering monomeric components and relative compositions, polymers can be tuned to provide specific mass and strength loss profiles that match a required function, such as wound healing or surgical aids. For example, absorbable materials for bone ties in orthopedics may feature mass degradation over a time period of 12 to 24 months, while short-term use sutures may resorb over three to four months or less.
Absorbable Polymers are Trusted Device Components
The textile market for absorbables is currently dominated by sutures and mesh material, although there is growing interest in absorbable polymers for new uses, such as tissue scaffolding and temporary or semi-permanent complete device platforms. The current design limitations on such devices generally stem from a dearth of materials able to satisfy more diverse combinations of mass and strength loss profile requirements with specific mechanical or physical conditions. Current commercially available products include surgical meshes, such as those for hernia repair, gynecological laparoscopies, and hemostasis, as well as staples, ligation clips, bone tacks and plates, and tissue barriers. However, the vast majority of absorbable products sold today are sutures. The first commercially available completely synthetic suture was composed of polyglycolide (PGA), and these sutures still endure in the market today. In the last few decades, suture composition has expanded to copolymers of glycolide with l-lactide, ε-caprolactone, polydioxanone, or trimethylene carbonate. Polyglycolide features high stiffness and mass loss in three to six months, while poly(l-lactide) features less stiffness than PGA, high tensile strength, and a much longer mass degradation time of one to three years. A mixture of 90% glycolide with 10% l-lactide (90/10 PGLA) is a classic suture composition, providing strength retention for two to four weeks and mass loss in three to four months. The component ε-caprolactone can be included for its reduction of the stiffness of pure glycolide material and increased degradation time, while polydioxanone offers increased compliance, strength retention over three to six weeks, and mass loss in less than six months. Trimethylene carbonate also improves flexibility when included as a block co-polymer with glycolide monomers. This copolymer degrades over the course of approximately seven months. It is clearly seen that by altering the constituents of copolymers, mass and strength degradation profiles can be tuned for specific functionalities.
As such, absorbable materials do not compose static tools of a toolbox, but can dynamically inform innovative medical device design. Exciting new uses for absorbables are being explored, including tissue scaffolds and platforms for complete device systems. Here, a particular case study of the synergy between polymer development and design of an absorbable ureteral stent is explored.
Ureteral stents are used to maintain the open geometry of the ureter by supporting the ureter after surgical operations in the vicinity or preventing blockage of urine flow through the ureter, among other applications. With lengths on the scale of 15 to 30 cm long, these stents are inserted temporarily and typically removed by pulling on a string left hanging exterior to the body or by cystoscopy, the insertion of a thin tube into the urethra. However, failure to follow up on stent removal, causing the so-called “forgotten stent,” can lead to complications such as encrustation, calcification, fragmentation, and migration of the stent. At best, these issues incur increased health care costs and must be resolved by more difficult surgical procedures, and at worst, can lead to patient morbidity either directly or indirectly from surgical complications.
Novel Absorbable Polymers Enable Unique Ureteral Stent Capabilities
Poly-Med, Inc., Anderson, SC, was engaged by its client, Adva-Tec, Inc., Greer, SC, to develop a ureteral stent that would degrade within an appropriate timeframe, towards the goal of ameliorating issues related to manual or surgical stent removal. The team approached this challenge by designing the ureteral stent from the ground up, in terms of developing three novel materials and incorporating them into the final stent design.
Three specialty absorbable polymers enabled the development of this stent. Stent requirements included elasticity and compliance, visibility under x-ray, and a mass degradation profile on the scale of a few weeks. Classic absorbable polymers posed problems when considered as a basis for the stent. The ubiquitous 90/10 PGLA composition was deemed too stiff and brittle to form the stent structure. Therefore, the team created a custom composition, 93/5/2 glycolide/ε-caprolactone/ trimethylene carbonate (TMC) (mole %), trademarked Glycoprene® MG-9. This novel material offered greater compliance and a somewhat shorter mass degradation profile, better matching the typical indwelling time period for a ureteral stent than traditional 90/10 PGLA while maintaining the mechanical properties required to support the stent structure. The material was extruded as a multifilament yarn, which was then circularly knitted around a coiled core. (See Figure 1)
This coiled core was composed of a secondary custom polymer created to provide radiopacity and compliance to the construct. Another classic absorbable, a copolymer of glycolide and ε-caprolactone, was considered for this role. However, 70/30 glycolide/ε-caprolactone (mole %) is slightly more brittle than an alternative, Glycoprene® MG-5, a block copolymer composed of 2.3/68.4/29.3 TMC-glycolide/ε-caprolactone (mole %). Due to the TMC blocks interspersed in the polymer chain structure, the second material shows increased flexibility and compliance. To impart radiopacity to the device, a radiopaque filler was added to it. This radiopaque monofilament was coiled around a long polytetrafluoroethylene strand (removed prior to packaging) to function as a core. Both materials have overlapping degradation profiles, allowing for a consistently degrading stent.
A final component material was developed as a coating that maintains a long-term degradation profile and high elasticity: Strataprene® SVG-12, a 14/35/17/34 TMC/ε-caprolactone/ glycolide-L-lactide (mole %) co-polymer. This coating material is entirely unique on the spectrum of absorbable polymers in terms of its suitability to form thin, elastic, and compliant coatings. From a process perspective, the coating step is simple, consisting of solvent-coating the stent construct via a continuous process. Drugs or bioactive agents could be loaded into the coating solution, for elution from the ureteral stent during indwelling.
Next-generation devices will be geared toward development of drug-eluting applications. For further reading on stent performance in a porcine model, see “Investigation of a Novel Degradable Ureteral Stent in a Porcine Model,” Hadaschik B.A., et. al., The Journal of Urology, Sep. 2008, 180(3), pp 1161-6.
Material Development Feeds Medical Device Innovation
The development of new absorbable polymers drove the design of this device platform, by imparting a degradation profile on par with the typical time period that ureteral stents are retained in the body, mechanical properties necessary for placement, and x-ray visualization ability. (See Figure 2) This stent represents the expansion of a ureteral stent functionality to preclude removal procedures and any associated complications due to forgotten stents, while also leading to next-generation work of drug-eluting ureteral stents for targeted dose delivery. A Phase I clinical evaluation of the ureteral stent will be conducted by Adva-Tec, Inc., beginning in the first quarter of 2014. Completion of the study is anticipated by the close of 2014.
Here, the customer was satisfied by a device platform that was enabled by three novel absorbable materials. Absorbable polymers have already proven to offer biocompatible options that have gained the trust of medical professionals and patients alike through standard use as sutures and surgical aids. By reducing health care costs via reducing surgical procedures and improving patient health, absorbable materials meet a vast range of needs. The future of absorbable materials is quite bright, as researchers continue to develop novel polymer chemistries that enable innovative and comprehensive device platforms for a vast range of previously untapped applications.
This article was written by Elizabeth Elvington, MS, Engineer, Poly-Med, Inc., Anderson, SC. For more information on Poly-Med, Inc., visit http://info.hotims.com/49745-163 . MD&M East, Booth 1484