Center for Modular Manufacturing of Structural Tissues

结构组织模块化制造中心

• 批准号: 10554848
• 负责人: Arnold Irwin Caplan
• 金额: $ 106.37万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10554848
• 关键词: Adoption; Animal Testing; Appearance; Automation; Basic Science; Biological; Biological Products; Biomedical Engineering; Bioreactors; Biosensing Techniques; Cartilage; Cell Culture Techniques; Cell physiology; Cells; Cessation of life; Characteristics; Clinical; Collaborations; Communities; Community Developments; Conditioned Culture Media; Congenital Abnormality; Data Management Resources; Development; Disease; Drug Screening; Engineering; Ensure; Evaluation; Evolution; Feedback; Feeds; Funding; Generations; Goals; Growth; Individual; Institute of Medicine (U.S.); Institutes; Instruction; Intervention; Knowledge; Laboratories; Mechanical Stimulation; Medical; Methods; Modeling; Molecular; Monitor; Pathway interactions; Patients; Pharmacologic Substance; Phenotype; Process; Property; Protocols documentation; Publications; Quality Control; Regenerative Medicine; Reporter; Resources; Risk; Running; Science; Services; Site-Directed Mutagenesis; System; Technology; Testing; Time; Tissue Engineering; Tissue constructs; Tissues; Training; Trauma; Vertebral column; base; biomedical imaging; bridge program; cohesion; cost effective; design; experience; flexibility; improved; innovation; innovative technologies; insight; manufacturing process; manufacturing process development; meetings; multimodality; new technology; non-invasive monitor; novel; optical sensor; personalized medicine; prevent; product development; program dissemination; programs; prototype; regenerative; research and development; scaffold; sensor; success; symposium; tool; user-friendly; web site

Despite significant advances over several decades, very few Tissue Engineered Medical Products (TEMPs) have been clinically or commercially successful, as a significant technology gap, known as the “Valley of Death”, has prevented their scalable, consistent and cost-effective manufacture. This proposal is for the competing renewal of the current “Case Center for Multimodal Evaluation of Engineered Cartilage.” There is a growing need for TEMPs in multiple applications. We therefore believe that now is the time for a bold shift from our original focus on cartilage-centric evaluation technologies to developing, demonstrating, and deploying novel technologies to enable Quality-by-Design manufacturing of a variety of structural tissues, and to, thus, bridge the Valley of Death. The goal of the Center is the adoption of our technologies by the TEMP community at large. Consequently, the Center, will be renamed “Center for Modular Manufacturing of Structural Tissues” (CM2OST), and will apply knowledge and technology developed during the first 5 years to manufacturing-oriented challenges. The Center will be a consortium between CWRU and the Advanced Regenerative Manufacturing Institute (ARMI), and will focus on technologies that enable scalable, modular, automated, closed (SMAC) manufacturing. The Specific Aims of the proposal are to 1) Assist our CPs and SPs by pushing the technologies developed at the Center out to them. 2) Develop a cohesive set of innovative technologies, methods, and protocols that enable structural tissue manufacturing through 4 TR&D projects, described below, and 3) Develop a new, state-of-the- art, training and dissemination program. Strategically, we will break the overall R&D program into 4 TR&Ds representing key components of the TEMP assembly-line model. TR&D-1 covers dynamic control of cell pheno- type and function during the manufacturing process, and development of tissue-specific sensors for dynamic non-invasive monitoring of cell phenotype and function. TR&D-2 will develop sensor-enabled scaffolds and novel optode-based optical sensors to automate cell seeding and to monitor metabolites and provide feedback on local and bulk medium conditions. TR&D-3 will develop bio-instructive bioreactors with integrated actuators and sen- sors for feedback control, and will physically integrate them with the Tissue Foundry, an ARMI prototype auto- mated TEMP assembly line. TR&D-4 will integrate sensors and actuators with the automation and data man- agement system of the Tissue Foundry and will perform a manufacturing demonstration run. Demonstrating technologies developed in the TR&Ds will provide insights into TEMP development, process development and automation, and expose unanticipated technology gaps. Each TR&D represents a step in the TEMP assembly- line model, thus, though the technologies are developed independently, each TR&D feeds into the next. TR&Ds, Collaborative and Service Projects synergize, integrating and exploiting each other’s technologies as they come online. CM2OST will be a national resource for collaborations and a platform for developing, testing, validating, and disseminating new technology, methods, and protocols for TEMP manufacturing.

尽管几十年来取得了重大进展，但很少有组织工程医疗产品(TEMP)能够 在临床上或商业上取得了成功，因为一个重大的技术差距，被称为“死亡之谷”，已经 阻碍了它们可扩展、一致和具有成本效益的生产。这项建议是为竞争性更新而提出的 目前的“工程软骨多模式评估案例中心”。有越来越多的人需要 多个应用程序中的临时工。因此，我们认为，现在是大胆改变我们最初的重点的时候了。 关于以软骨为中心的评估技术，以开发、演示和部署新技术 实现各种结构组织的按设计质量制造，从而架起死亡之谷的桥梁。 该中心的目标是让广大临时工社区采用我们的技术。因此， 中心，将更名为结构组织模块化制造中心(CM2OST)，并将适用 前5年发展起来的知识和技术，以应对制造业方面的挑战。《中心》 将是CWRU和先进再生制造研究所(ARMI)的联盟，并将 专注于支持可扩展、模块化、自动化、封闭式(SMAC)制造的技术。具体的 该提案的目的是1)通过推动中心开发的技术来帮助我们的CPS和SPS 向他们伸出援手。2)开发一套具有凝聚力的创新技术、方法和协议，使 通过4个研发项目制造结构组织，如下所述，以及3)开发一种新的、最先进的- 艺术、培训和传播计划。在战略上，我们将把整个研发计划分解为4个研发项目 代表临时装配线模型的关键组件。T&D-1涵盖了对细胞表型的动态控制。 制造过程中的类型和功能，以及动态组织特异性传感器的开发 细胞表型和功能的非侵入性监测。T&D-2将开发传感器启用的支架和新型 基于光电的光学传感器，用于自动化细胞播种和监测代谢物并提供局部反馈 和散装介质条件。R&D-3将开发具有集成执行器和感应器的生物教育生物反应器。 SOR用于反馈控制，并将它们与Tablet Foundry进行物理集成，这是ARMI的自动原型- 配套的临时装配线。T&D-4将传感器和执行器与自动化和数据城域网集成在一起- 组织铸造厂的管理系统，并将进行制造示范运行。演示 研发中开发的技术将提供对临时开发、流程开发和 自动化，并暴露意想不到的技术差距。每一次研发都代表着临时工组装中的一个步骤- 因此，尽管这些技术是独立开发的，但每一项研发都是对下一项技术的补充。R&D， 协作和服务项目在彼此的技术出现时进行协同、集成和利用 上网。CM2OST将成为国家协作资源和开发、测试、验证、 传播临时工制造的新技术、新方法和新协议。