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) 临床或商业上取得成功，因为存在被称为“死亡之谷”的重大技术差距 阻碍了其可扩展、一致且具有成本效益的制造。本提案适用于竞争性续订 当前的“工程软骨多模式评估案例中心”。人们越来越需要 多个应用程序中的 TEMP。因此，我们认为现在是时候大胆转变我们最初的重点了 以软骨为中心的评估技术来开发、演示和部署新技术 实现各种结构组织的质量源于设计制造，从而跨越死亡之谷。 该中心的目标是让整个 TEMP 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），并将申请 前 5 年开发的知识和技术应对面向制造的挑战。中心 将是 CWRU 和先进再生制造研究所 (ARMI) 之间的联盟，并将 专注于实现可扩展、模块化、自动化、封闭式 (SMAC) 制造的技术。具体 该提案的目的是 1) 通过推动中心开发的技术来协助我们的 CP 和 SP 出给他们。 2) 开发一套有凝聚力的创新技术、方法和协议，使 通过如下所述的 4 个 TR&D 项目进行结构组织制造，以及 3) 开发一种新的、最先进的- 艺术、培训和传播计划。战略上，我们将把整体研发计划分解为4个TR&D 代表 TEMP 装配线模型的关键组件。 TR&D-1 涵盖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 无创监测细胞表型和功能。 TR&D-2 将开发传感器支架和新型支架 基于光极的光学传感器可自动进行细胞接种并监测代谢物并提供局部反馈 和散装介质条件。 TR&D-3 将开发具有集成执行器和传感器的生物指导生物反应器 反馈控制，并将它们与 Tissue Foundry（一个 ARMI 原型自动 配套的TEMP装配线。 TR&D-4 将传感器和执行器与自动化和数据管理集成 组织铸造厂的管理系统并将进行制造示范运行。示范 TR&D 中开发的技术将为 TEMP 开发、工艺开发和 自动化，并暴露意想不到的技术差距。每个 TR&D 代表 TEMP 装配中的一个步骤 - 因此，尽管这些技术是独立开发的，但每项 TR&D 都会相互影响。 TR&D， 协作和服务项目协同、集成和利用彼此的技术 在线的。 CM2OST 将成为国家合作资源和开发、测试、验证、 传播 TEMP 制造的新技术、方法和协议。