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，但很少有组织工程的医疗产品（TEMP）拥有 在临床或商业上成功，作为一个重要的技术差距，称为“死亡谷” 防止其可扩展，一致且具有成本效益的制造。该提议是针对竞争的续订 当前的“工程软骨多模式评估案例中心”越来越需要 在多个应用程序中的温度。因此，我们认为现在是从我们最初的重点大胆转变的时候 以软骨为中心的评估技术开发，演示和部署新型技术 启用各种结构组织的质量制造，从而弥合死亡谷。 该中心的目的是整个临时社区采用我们的技术。因此， 中心将重命名为“结构组织模块化制造中心”（CM2OST），并将应用 知识和技术在最初的5年中发展为面向制造业的挑战。中心 将是CWRU与高级再生制造学院（ARMI）之间的财团，将 专注于启用可扩展，模块化，自动化，封闭（SMAC）制造的技术。具体 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SP 向他们出去。 2）开发一套具有凝聚力的创新技术，方法和协议，以实现 通过以下四个TR＆D项目进行结构组织制造，以及3）开发一个新的，最先进的 艺术，培训和传播计划。从战略上讲，我们将把整个研发计划分为4个TR＆D 代表温度组装线模型的关键组件。 TR＆D-1涵盖了细胞态的动态控制 制造过程中的类型和功能，以及动态的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。 TR＆D-2将开发启用传感器的脚手架和新颖 基于optode的光传感器可自动化细胞播种并监测代谢物，并提供有关局部的反馈 和散装中等状况。 TR＆D-3将开发具有综合执行器和SEN-的生物教学生物反应器 用于反馈控制的SOR，并将它们与组织铸造物进行物理整合，Armi原型自动 伴侣温度组装线。 TR＆D-4将将传感器和执行器与自动化和数据man- 组织铸造厂的染色系统，并将进行制造示范运行。展示 在TR＆D中开发的技术将为温度开发，过程开发和 自动化，并揭示意外的技术差距。每个TR＆D代表温度组件中的一步 线模型，因此，尽管这些技术是独立开发的，但每个TR＆D都馈入下一个技术。 tr＆d， 协作和服务项目协同，整合和利用彼此的技术 在线的。 CM2OST将是合作的国家资源，也将是开发，测试，验证， 并传播用于临时制造的新技术，方法和协议。