A Method for Reduction of Bioburden in Bone Allografts

减少同种异体骨生物负荷的方法

• 批准号: 6883835
• 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: 2005-03-14 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6883835
• 关键词: Bacillus stearothermophilus; Bacillus subtilis; antiinfective agents; biomechanics; bone; bone density; bone preservation; bone transplantation; carbon dioxide; gamma radiation; homologous transplantation; human tissue; lyophilization; microorganism growth; spores; technology /technique development

DESCRIPTION (provided by applicant): A new method of bone tissue terminal sterilization using supercritical CO2 is proposed for accomplishing industrially acceptable levels of bacterial inactivation. Preliminary experiments reveal that unlike gamma-irradiation, supercritical CO2 does not reduce the mechanical strength of bone. Recent events related to unsafe tissue supplies highlight the need for a technology that can terminally sterilize tissue while maintaining the essential properties of the tissue. The tissue banking industry has invested in costly clean room technologies, complicated and unvalidated non-terminal disinfection techniques to respond to impending FDA regulation. Our preliminary evidence suggests that sterilization using our proprietary method is a viable solution to this ongoing dilemma. The specific aims of this proposal are: 1. To develop a procedure for terminal sterilization of bone tissues with supercritical carbon dioxide. 2. To analyze post-sterilization bone tissue samples for potential material alterations and compare them with untreated and gamma irradiated samples. Introduction of CO2 sterilization to the tissue bank industry can be accomplished quickly once a satisfactory set of tests with bioindicators is accomplished. There is still no FDA sterilization regulation in the tissue bank industry today. Current gamma sterilization has about a 3 log reduction of the B. pumilus bio-indicator from a 106bioburden. Higher doses of gamma can severely weaken bone to an unusable condition. Current work at NovaSterilis has accomplished sterilization of spiked bone tissue by demonstrating total inactivation of the bioindicators: B. subtilis and stearothermophilus endospores. The long-term objective of this project is to develop a commercially viable sterilization method that would be compatible with human bone tissues processed for transplantation where cell viability is not a concern and would eventually replace gamma radiation sterilization. The new CO2 based sterilization technology produces no environmentally hazardous byproducts, and should be readily transferred to the biomedical industry. The commercial sterilization reactor would use carbon dioxide in a closed-system (similar to many CO2 -based extraction systems) where used CO2 would be purified and reused again (complete recycling system).

描述(由申请人提供)：为了达到工业上可接受的细菌灭活水平，提出了一种使用超临界二氧化碳进行骨组织终端灭菌的新方法。初步实验表明，与伽马辐射不同，超临界二氧化碳不会降低骨骼的机械强度。最近发生的与不安全组织供应有关的事件突显了对一种技术的需求，该技术可以在保持组织的基本属性的同时对组织进行最终消毒。组织银行行业投资了昂贵的洁净室技术，复杂且未经验证的非终端消毒技术，以应对FDA即将出台的法规。我们的初步证据表明，使用我们的专有方法进行绝育是解决这一持续困境的可行方案。 这项建议的具体目标是： 1.建立超临界二氧化碳终末灭菌骨组织的方法。 2.分析灭菌后骨组织标本潜在的材料变化，并将其与未经处理和伽玛射线照射的标本进行比较。 一旦完成了一套令人满意的生物指示剂测试，就可以迅速将二氧化碳灭菌引入组织库行业。今天，组织银行行业仍然没有FDA的灭菌法规。目前的伽马灭菌法使短小芽孢杆菌的生物指示剂从106个生物量减少了大约3个对数。较高剂量的伽马会严重削弱骨骼，使其无法使用。NovaSterilis目前的工作已经通过展示生物指示剂枯草杆菌和嗜热硬脂菌内孢子的完全灭活来完成对添加的骨组织的灭菌。 该项目的长期目标是开发一种商业上可行的灭菌方法，该方法将与用于移植的人骨组织兼容，在这种情况下，细胞活性不是问题，并最终将取代伽马辐射灭菌。基于二氧化碳的新灭菌技术不会产生对环境有害的副产品，应该很容易转移到生物医药行业。商业灭菌反应器将在封闭系统中使用二氧化碳(类似于许多基于二氧化碳的提取系统)，使用过的二氧化碳将被提纯并再次重复使用(完整的循环系统)。