Terminal Sterilization of Tendon Allografts with C02

使用 C02 对同种异体肌腱进行最终灭菌

• 批准号: 6990187
• 负责人: TIMOTHY W CHRISTENSEN
• 金额: $ 10万
• 依托单位: NOVASTERILIS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-05 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6990187
• 关键词: antisepsis; biomechanics; carbon dioxide; disease /disorder prevention /control; homologous transplantation; human tissue; structural biology; technology /technique development; tendons; tissue /cell preparation; tissue resource /registry; transplantation disease transmission

DESCRIPTION (provided by applicant): Terminal sterilization of tendon allografts to the same levels called for in medical devices is currently all but non-existent. Terminal sterilization using ethylene oxide gas leaves toxic residues and negatively impacts the probability of positive outcomes following ACL surgeries. Gamma irradiation is used to sterilize grafts but at the irradiation levels sufficient to achieve sterilization the tendon is rendered unusable because separation of collagen bundles and denatured proteins result in significant weakening of the graft. An ideal method for sterilization of tendon allograft material would be one that is terminal, non-toxic, retains the essential properties of the allograft, and is validated to achieve sterility assurance level of 10-6 (the same level required for medical devices). Our preliminary experiments indicate that sterilization by our supercritical CO2 process represents a viable solution to answer the pressing need to terminally sterilize tendon allograft material. We request support to develop a validated terminal sterilization process for tendon allografts utilizing supercritical CO2. The specific aims of this proposal are (1) To develop a procedure for terminal sterilization of tendon tissues with supercritical carbon dioxide; (2) To analyze post-sterilization tendon tissue samples for potential biomechanical alterations and compare them with untreated. The long-term objective of this project is to develop a commercially viable terminal sterilization method that would be compatible with human soft tissues and would eventually add a terminal sterilization component to current tissue bank practices. Phase II studies will consist of comprehensive testing to verify inactivation of viral and fungal contaminates in tendon as well as tests using animal models to evaluate histological and biomechanical changes in supercritical CO2 sterilized implanted allograft tendons through the phases of graft necrosis, revascularization, fibroblast invasion and collagen synthesis. Furthermore this technology may be expanded for use in other tissues where donor cell viability is not a concern.

描述(由申请人提供)：目前几乎不存在对同种异体肌腱移植物进行终端灭菌，达到医疗器械中要求的相同水平。使用环氧乙烷气体的终端绝育会留下有毒残留物，并对前交叉韧带手术后阳性结果的可能性产生负面影响。伽玛辐射用于对移植物进行灭菌，但在足以实现灭菌的辐射水平上，肌腱变得不可用，因为胶原束和变性蛋白的分离会导致移植物的显着削弱。理想的同种异体肌腱材料灭菌方法是终端、无毒、保留同种异体肌腱的基本特性，并经验证达到10-6的无菌保证水平(与医疗器械相同的水平)。我们的初步实验表明，我们的超临界二氧化碳灭菌工艺是一种可行的解决方案，可以满足对同种异体肌腱移植材料进行最终灭菌的迫切需求。我们请求支持利用超临界二氧化碳为同种异体肌腱移植物开发有效的终端灭菌工艺。这项建议的具体目的是(1)开发一种用超临界二氧化碳对肌腱组织进行末端灭菌的程序；(2)分析灭菌后的肌腱组织样本是否存在潜在的生物力学变化，并将其与未经处理的肌腱组织进行比较。该项目的长期目标是开发一种商业上可行的终端灭菌方法，该方法将与人类软组织兼容，并最终将终端灭菌成分添加到目前的组织库实践中。第二阶段的研究将包括全面的测试，以验证肌腱中病毒和真菌污染物的灭活，以及使用动物模型测试，以评估超临界二氧化碳灭菌的同种异体肌腱在移植物坏死、血管重建、成纤维细胞侵袭和胶原合成等阶段的组织学和生物力学变化。此外，这项技术可能会扩展到供体细胞活性不是问题的其他组织中。