SBIR Phase II: Development of a Tissue Engineered Trachea

这个小型企业创新研究(SBIR)第二阶段项目的更广泛影响/商业潜力集中在开发可定制的组织工程气管植入物，用于气管移植和重建手术。目前对这些患者的手术解决方案受限于合适的身体组织的可用性问题，以及由于血运重建和免疫排斥问题而导致的移植组织长期存活不令人满意的问题。惰性生物材料支架和自体细胞的结合避免了对移植物排斥反应的任何担忧，同时允许可靠地生产气管移植物。纳米纤维解决方案公司预计，这种新设备每年将实现多达6500次生命拯救过程。成功的第二阶段项目将展示纳米纤维气管植入物的长期性能和在大型动物模型中的作用机制，以及FDA启动临床试验的人道主义设备豁免(HDE)申请。这种气管植入物产品解决了价值6亿美元的机会。基于该技术平台的其他组织工程产品解决了数十亿美元的市场机会。拟议的项目重点是开发一种可定制的组织工程气管植入物，用于气管移植和重建手术。气管具有挑战性的机械和生物要求，尽管进行了多次尝试，但目前还没有功能齐全的人工气管。全合成的气管支架种植了从患者S骨髓中提取的自体干细胞。为了准备FDA提交的文件和初步的人体临床试验，我们将在这项第二阶段工作中实现三个技术目标：1)优化封闭系统的使用，使细胞能够在支架上均匀种植；2)为在气管移植物上放置支撑肋开发一种商业化的制造工艺；3)阐明术中植入的气管植入物在体内的气管再生机制。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is focused on developing a customizable tissue engineered tracheal implant for tracheal transplantation and reconstruction surgery. Current surgical solutions for these patients are limited by problems with the availability of suitable cadaveric tissue, as well as with unsatisfactory long-term survival of the engrafted tissues due to issues with both revascularization and immune rejection. The combination of an inert biomaterial scaffold and autologous cells avoids any concerns with graft rejection, while allowing for the reliable production of tracheal grafts. Nanofiber Solutions expects this new device will enable as many as 6,500 life-saving procedures annually. A successful Phase 2 project will demonstrate long-term performance of the nanofiber tracheal implant and the mechanisms of action in a large animal model as well as a humanitarian device exemption (HDE) application with the FDA to initiate a clinical trial. This trachea implant product addresses a $600 million dollar opportunity. Other tissue engineered products based on this technology platform address billions of dollars more in market opportunity.The proposed project is focused on developing a customizable tissue engineered tracheal implant for tracheal transplantation and reconstruction surgery. The trachea has challenging mechanical and biological requirements, and despite many attempts there currently is no fully functional artificial trachea. The fully synthetic tracheal scaffold is seeded with autologous stem cells harvested from the patient?s bone marrow. To prepare for an FDA submission and initial human clinical trials, we will accomplish three technical objectives in this Phase II work: 1) Optimize the use of a closed system, disposable seeding chamber to allow uniform cell seeding throughout the scaffold, 2) Develop a commercial manufacturing process for the production and placement of support ribs on the tracheal graft, and 3) Elucidate mechanisms of tracheal regeneration in vivo of intraoperatively seeded tracheal implants.