Supercritical sterilisation for biological tissue transplant products

生物组织移植产品的超临界灭菌

• 批准号: 2276891
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2276891
• 关键词: Supercritical; sterilisation; biological; tissue; transplant

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.

翻译任何组织衍生产品的重大挑战之一是在不损害结构和生化完整性以及临床表现的情况下确保无菌。我们最近开发了一种供体角膜重建疗法。然而，对于患者使用，该产品将需要终端灭菌过程，而目前的方法(例如环氧乙烷和辐射)会导致组织衍生产品中包含的生物分子发生变化，这促使替代产品的需求。超临界二氧化碳(ScCO2)是无毒、非易燃、非活性的，不会留下任何有毒残留物。二氧化碳是一种超临界流体，高于其临界压力和温度(73.8巴和31.1度)。这些条件确保了scCO2可以在低温下使用，从而可以避免敏感分子的热降解。到目前为止，scCO2已被用于杀菌脱细胞动物组织(牛骨和猪心脏瓣膜)和天然聚合物水凝胶(海藻酸盐和胶原)，但尚未用于保存的人或动物组织。该项目将开发一种新的超临界二氧化碳灭菌工艺，以产生具有长期储存能力和现成使用能力的无菌、干燥的纸巾产品。这将通过(I)验证scCO2对细菌孢子的灭活；(Ii)调查scCO2加工对保存的生物组织的影响；(Iii)确定从研究环境转换到无菌组织产品的GMP过程的障碍；以及(Iv)开发一种新的scCO2工艺来对保存的生物组织进行灭菌。该项目将详细、深入地开发和验证一种对保存的组织产品进行灭菌的新技术，这是监管部门批准和临床翻译所需的。重要的是，为了协助该项目的翻译，将与工业合作伙伴NuVision合作，绘制实现监管批准的最佳制造路线的工艺图。