Rapid developments in surgical and implantable device technology pose challenges for current sterilization methods. This is particularly true for environment-sensitive biopolymers. The major sterilization methods used in hospitals include moist heat steam autoclaves, ethylene oxide gas, gamma irradiation and gas plasma. However, no single process is suitable for sterilizing all medical devices. Specifically for biopolymers, high temperatures (for thermally sensitive materials), toxic or oxidative chemical agents, and/or radiation may degrade performance and lower the biocompatibility of the biopolymers. Because of these limitations, the next generations of polymeric medical devices and heat sensitive biomaterials require new sterilization methods.
Terminal sterilization of manufactured products is a critical issue in the medical device and pharmaceutical industries. Because current sterilization methods pose significant drawbacks in specific biomedical applications, SC-CO2 (supercritical-carbon dioxide) technology is a promising alternative. SC-CO2 sterilization is a novel low temperature and biocompatible sterilization process. There is potential for using supercritical CO2 technology in the emerging field of polymeric biomedical materials, encompassing both synthetic and natural polymers, and packaged materials. CO2-based fluids have been tested for both inactivation and sterilization of organisms and compatibility with biomaterials, CO2-based fluids with trace levels of additives are successful in killing organisms such as B. pumilus spores. Several medical grade polymers have been processed with CO2 without degrading chemical and mechanical properties. By translating research into practice, CO2 processing will be a suitable alternative for sterilizing thermally sensitive materials. SC-CO2 has shown tremendous potential for the modification and processing of polymers, including common synthetic polymers.
The biocidal and sterilizing effects of high-pressure CO2 mixtures have been quantified for various species of bacteria, and these results have recently been summarized. CO2 technology is attractive in part because CO2 is non-flammable, non-toxic, physiologically safe, chemically inert and readily available. When heated and compressed above its critical point (7.38 MPa and 304.2 K) CO2 exhibits a liquid-like density (0.6-1.0×10−3 kg·m−3) but gas-like diffusivity (10−7-10−8 m2s−1) and viscosity (3-7×10−5 N·s·m−2). Because there is no vapor-liquid interface for pure SC-CO2, there are no surface tension considerations. For two-phase mixtures (e.g. CO2+water) near the CO2 critical point, the surface tension is quite low. These properties allow CO2 to penetrate porous structures easily. Typical CO2 processing temperatures range up to 40° C., so there is the potential for developing a low-temperature sterilization technology. Research has shown that compressed CO2 kills many clinically relevant gram-positive vegetative bacteria (e.g. Listeria monocytogenes, Staphylococcus aureus, and Enterococcus faecalis) and gram-negative vegetative bacteria (e.g. Salmonella typhimurium, E. coli, and Pseudomonas aeruginosa). Bacterial spores can also be sterilized with this process. A 6-log reduction of B. pumilus, B. atrophaeus, and G. stearothermophilus spores has been achieved at relatively low temperatures using SC-CO2 (40° C., 27.58 MPa for 4 hours).
Significant attention has been focused on environment-responsive hydrogels because of their applications for stimuli-responsive drug delivery, in which they show changes in swelling behavior according to the external environment. The external aqueous environment affects the swelling and water content of any specific gel. These properties also depend on the ionic character of the gel, electrostatic forces, thermodynamic activity, and nature of the polymer. The presence of thermodynamically active functional groups on polymer chains makes these hydrogels sensitive to environmental factors. Incorporating acidic or basic groups render a hydrogel pH sensitive. The ability to control changes in the properties of a hydrogel leads to the potential for solving significant medical problems that cannot be addressed with conventional engineering plastics. Crosslinked poly(acrylic acid) and its copolymers, form a class of interesting hydrogels that can absorb, swell and retain aqueous solutions up to hundreds or thousands times their own weight, even under pressure.
As such, a need exists for a method of sterilizing a hydrogel polymer, particularly a biocompatible hydrogel polymer, from bacteria (e.g., S. aureus and E. coli).