Polymers that exhibit shape-memory effect (SME) are an important class of materials in medicine, especially for minimally invasive deployment of devices. Professor Subbu Venkatraman and his group from School of Materials Science and Engineering, Nanyang Technological University presented a review article surveying the clinical applications of the SME and addressing critically the question of its utility in implantable devices. Their work, entitled "Biomedical applications of shape-memory polymers: How practically useful are they?", was published in SCIENCE CHINA Chemistry.2014, Vol 57(4).
The shape-memory effect, as exhibited by metal alloys such as nitinol as well as many polymers, is the ability of a material to change its dimension in a predefined way in response to an external stimulus. For the many medical implants that can be deployed in the body using minimally invasive means, the implant dimension should be small during deployment and must regain a larger shape after deployment. Examples of such devices include stents, heart valves and septal defect occluders. As the range of available materials expands, so will the range of applications. Although the filed has been long dominated by one single material, nitinol (an alloy of nickel and titanium), polymers are challenging this dominance because they offer more functionality than simple ease of deployment.
For instance, a polymer that exhibits the SME could be biodegradable as well as drug-eluting, two functions that are impossible to achieve with nitinol. Thus, a biodegradable implant made of SMP loaded with therapeutic agent could be compressed and delivered inside the body, still in its compact form, via minimally invasive surgery. Once the implant is placed in the targeted site, it can be simultaneously recovered to its larger primary shape (triggered by body heat or other means) and one or more drugs can be released from the SMP matrix. Finally, the implant degrades, which eliminates the need for a second surgery for explanation. Developing this novel concept into practice has engaged the attention of researchers from both academia and industry, as reflected in the rapidly increasing number of publications on SMPs since 2003.
Over the past decade, various types of SMPs have been developed. A generalized SMP architecture is depicted in figure below. Based on this diagram, SMPs can be typically broadly categorized by their stimulus into two main streams: thermally and athermally induced SMEs. A thermoresponsive SMP can be thermally actuated by increasing the environment temperature above its thermal transition by either direct or indirect (i.e. magnetic or electrical) heating. Athermoresponsive SMP, however, can be actuated by stimuli other heat (e.g. light and solvent).
Despite of the numerous SMPs being developed, the kinetics of shape recovery is one of issues needed to be addressed to accelerate the rate of translation of the concept to approved products. Stent is one of the main targets for SMPs development in medical devices. For instance, a laser-actuated SMP stent prototype fabricated from polyurethane was developed by Baer et al. The stent was crimped over a fiber-optic light diffuser coupled to an IR diode laser for photo-thermal actuation of the stent. Under zero flow condition, the stent was fully recovered / expanded within 6 minutes in vitro. In general, the speed of recovery is more important than the extent of recovery for SMP stents. The crimped (or sheathed) stent must recover to anchor itself in the vessel within 1-2 min. Therefore, options such as water-induced or light-induced SMEs are not the best options for stents. Generally, the SMP stents based on nitinol are pre-recovered but constrained in a sheath until deployment at the site by slow sheath removal. This is the best way to meet the rate-of-recovery requirements.
Another issue to be addressed is sterilization for SMP-based medical devices. All medical devices must undergo sterilization before they can be used clinically. Conventional methods of sterilization listed in the US FDA guide include exposure to steam, ethylene oxide (EtO), irradiation (gamma or e-beam) and plasma treatment. Virtually all methods have their own merits and disadvantages, depending on the mode of SME activation that is envisaged. Therefore, identifying an appropriate process that can achieve the required sterility without compromising the SMP properties is challenging. In general, autoclave (steam) sterilization is not suitable for use with thermal SMPs due to its high temperature range, which can delete the shape-memory effect and also damage drugs that are embedded within the polymer matrix. By far, EtO sterilization is the gold standard of the low-temperature sterilization methods. Numerous research teams have studied the impact of EtO sterilization of various polymeric materials and have obtained promising results, with maintenance of the shape-memory effect. However, due to moisture ingress during EtO sterilization due to the high humidity levels usually employed, this method is not suitable for water-activated SMPs. Currently, unconventional low-temperature sterilization methods are under development such as noxilizer (room temperature NO2-based sterilization technology) and dense carbon dioxide gas sterilization. Both techniques can be performed at even lower temperatures (25-34°C) than the conventional sterilization methods. This possibility would eliminate any potential for premature activation of SME during sterilization, even when the activation temperature is at body temperature.
Overall, SMPs are an important class of materials in medicine. Nevertheless, we find that the rate of translation of the concept to approved products is extremely low, with mostly nitinol-based devices being approved. Further success will depend upon overcoming the problem of shape-memory loss during storage and sterilization, as well as upon improving the kinetics of shape recovery.