X-ray Irradiator for Tissue Engineering Applications

组织工程旨在开发组织替代品，以解决日益增长的供体组织和器官短缺问题。组织替代物的发展涉及将人类细胞（干细胞、祖细胞或分化细胞）与多孔支架相结合，多孔支架为细胞附着、增殖和分化提供了3D基质。这些支架是由合成聚合物、天然聚合物和/或生物陶瓷制成的泡沫，必须是无菌的，这包括在播种人类细胞之前去除、杀死或使微生物污染失活。由胶原蛋白、弹性蛋白和透明质酸等天然聚合物制成的支架适合于组织工程应用，因为它们的蛋白质结构中编码了丰富的细胞结合基序，然而，它们不能使用高压灭菌技术进行灭菌，因为高温和高压条件会使这些生物分子变性和降解。同样，由于环氧乙烷的毒性，可以避免使用，而70%的乙醇不能充分消除亲水病毒和细菌孢子。25kGy剂量的γ辐照在商业上用于对医疗器械进行灭菌，是对天然聚合物支架进行灭菌的首选方法。大多伦多汉密尔顿地区（GTHA）的组织工程研究人员一直在使用多伦多大学的伽马辐照器对他们的支架进行消毒。这个系统提供了负担得起的消毒服务。然而，该辐照器计划于2023年3月退役，商业消毒供应商收取高昂的费用，使学术研究人员无法使用他们的服务。迫切需要一种新的、更安全的、负担得起的辐照灭菌系统，以继续支持加拿大，特别是GTHA的学术研究人员的研究项目。该提案旨在资助一个x射线辐照器，为约克大学的学术研究人员提供负担得起的服务，以继续进行关键的组织工程研究。

Tissue engineering aims to develop tissue substitutes to address the ever-increasing donor tissue and organ shortage. The development of tissue replacements involves combining human cells (stem cells, progenitors or differentiated cells) with porous scaffolds which provide a 3D substrate for cell attachment, proliferation and differentiation. These scaffolds are foamed from either synthetic polymers, natural polymers and/or bioceramics and must be sterile, which involves removal, killing or deactivation of microbial contamination, before seeding with human cells. Scaffolds made from natural polymers like collagen, elastin and hyaluronic acid are suitable for tissue engineering applications due to the abundance of cell binding motifs encoded in their protein structure, however, they can not be sterilized using autoclave techniques as elevated heat and pressure conditions denature and degrade these biomolecules. Similarly, ethylene oxide is avoided due to its toxicity while 70% ethanol does not adequately eliminate hydrophilic viruses and bacterial spores. Gamma-irradiation at 25kGy dose is commercially used to sterilize medical devices and is the preferred method to sterilize natural polymer scaffolds. Tissue engineering researchers in the Greater Toronto Hamilton Area (GTHA) have been using the gamma irradiator at the University of Toronto to sterilize their scaffolds. This system was providing affordable sterilization services. However, this irradiator is scheduled to be decommissioned in March 2023 and commercial sterilization providers charge high fees which preclude academic researchers from using their services. A new, safer and affordable irradiation sterilization system is urgently needed to continue to support the research programs of academic researchers in Canada, and specifically in the GTHA. This proposal seeks to fund an X-ray irradiator to establish an affordable service at York University for academic researchers to continue critical tissue engineering research.