Supercritical sterilisation for biological tissue transplant products

One of the significant challenges for translation of any tissue derived products is to ensure sterility without compromising structural and biochemical integrity and clinical performance. We have recently developed a donor cornea reconstruction therapy. However, for use in patients, this product will require a terminal sterilisation process and current methods (e.g. ethylene oxide and irradiation) cause alterations in biomolecules contained within tissue derived products, prompting the need for alternatives. Supercritical carbon dioxide (scCO2) is non-toxic, non-flammable, non-reactive and does not leave behind any toxic residues. Carbon dioxide is a supercritical fluid above its critical pressure and temperature (73.8 bar and 31.1degree). These conditions ensure that scCO2 can be used at low temperatures and thus thermal degradation of sensitive molecules can be avoided. To date, scCO2 has been applied to sterilise decellularised animal tissues (bovine bone and porcine heart valves) and natural polymeric hydrogels (alginate and collagen) but has not been used with preserved human or animal tissues. This project will develop a new supercritical carbon dioxide sterilisation process to generate sterile, dry tissue products with long term storage capability and off-the-shelf use. This will be achieved by (i) validating scCO2 inactivation of bacterial spores; (ii) investigating scCO2 processing impacts on preserved biological tissues; (iii) identifying barriers to translation from the research environment to a GMP process of sterilised tissue products and (iv) developing a new scCO2 process to sterilise preserved biological tissue. This project will provide detailed, in depth development and validation of a new technology to sterilise preserved tissue products, required for regulatory approval and clinical translation. Importantly, to aid in the translation aspects of this project, process mapping of the optimal manufacturing route for achieving regulatory approval will be undertaken in collaboration with the industrial partner, NuVision.