Advanced Manufacturing of Regenerative Extracellular Matrix Scaffolds

再生细胞外基质支架的先进制造

• 批准号: 10001351
• 负责人: Stephen F. Badylak
• 金额: $ 59.99万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001351
• 关键词: Advanced; Manufacturing; Regenerative; Extracellular; Matrix

The convergence of regenerative and personalized medicine has the potential to revolutionize treatment of a wide range of diseases and traumatic injuries by harnessing a patient’s own immune system together with extracellular matrix (ECM) scaffolds to achieve tissue repair. However, the advances being made in academic research have been slow to translate to the clinic, due in large part to the inability to manufacture these therapies in a standardized, reproducible and patient-specific manner. The advanced manufacturing of complex biologic products can solve this problem, serving as the enabling technology for these emerging applications. Yet while advanced manufacturing of synthetic polymer and titanium implants has already received FDA-approval, the 3D printing of ECM and cells has proved far more challenging. Here we propose to develop new technologies critically needed to translate regenerative ECM scaffolds in to the clinic by addressing key manufacturing needs for ECM scaffold 3D printing. Specifically, we have identified in process monitoring, multiscale ECM scaffold fabrication and decellularized ECM bioinks as critical capabilities. To do this we will leverage our expertise in near-IR imaging, decellularized ECM, and 3D biofabrication. The work to be conducted is summarized in three specific aims. One, to engineer an integrated 3D bioprinting and OCT imaging system to enable in process monitoring and real-time feedback during biofabrication. The goal of this aim is to enable nondestructive 3D imaging of ECM scaffolds during the 3D bioprinting process in order to rapidly assess success/failure. Two, to develop a multi-scale biofabrication process that can combine multiple 3D printing methods in a single construct to recapitulate native tissue composition and architecture. The goal of this aim is to address the challenge of building large volumetric ECM scaffolds that also require nano- to micro- scale resolution to form intricate anatomical structures. Three, to establish the ability to 3D bioprint regenerative ECM scaffolds for volumetric muscle repair, matched to patient-specific anatomical defects. The goal of this aim is to transition our existing regenerative ECM scaffolds for volumetric muscle repair from a manual fabrication process to an automated, advanced manufacturing process and use CT and MRI imaging data to match patient-specific tissue defects. This would have profound consequences by leading towards clinically-relevant therapeutic strategies to regenerate tissues and develop the advanced manufacturing capabilities necessary to achieve industrial scale-up and translation.

再生医学和个性化医学的融合有可能彻底改变疾病的治疗 通过利用患者自身的免疫系统和 细胞外基质（ECM）支架以实现组织修复。然而，学术上正在取得的进步 研究成果转化为临床的速度很慢，很大程度上是由于无法制造这些 以标准化、可重复且针对患者的特定方式进行治疗。先进制造 复杂的生物产品可以解决这个问题，作为这些新兴产品的支持技术 应用程序。然而，尽管合成聚合物和钛植入物的先进制造已经 获得 FDA 批准后，ECM 和细胞的 3D 打印被证明更具挑战性。在此我们建议 开发将再生 ECM 支架转化为临床所需的新技术 满足 ECM 支架 3D 打印的关键制造需求。具体来说，我们已经在过程中确定了 监测、多尺度 ECM 支架制造和脱细胞 ECM 生物墨水是关键能力。要做的事 为此，我们将利用我们在近红外成像、脱细胞 ECM 和 3D 生物制造方面的专业知识。该工作至 所进行的工作概括为三个具体目标。一、设计集成的 3D 生物打印和 OCT 成像系统可在生物制造过程中实现过程监控和实时反馈。此举的目标 目的是在 3D 生物打印过程中实现 ECM 支架的无损 3D 成像，以便 快速评估成功/失败。二、开发可结合多种技术的多尺度生物制造工艺 单一结构中的 3D 打印方法可重现天然组织的组成和结构。目标是 这个目标是解决构建大体积 ECM 支架的挑战，该支架也需要纳米到微米 尺度分辨率形成复杂的解剖结构。三、建立3D生物打印能力 用于体积肌肉修复的再生 ECM 支架，与患者特定的解剖缺陷相匹配。这 这一目标的目标是将我们现有的用于体积肌肉修复的再生 ECM 支架从 手动制造工艺转变为自动化、先进的制造工艺并使用 CT 和 MRI 成像 数据以匹配患者特定的组织缺陷。这将产生深远的影响，导致 临床相关的组织再生治疗策略和开发先进制造 实现产业规模化和转化所需的能力。