Advanced Manufacturing of Regenerative Extracellular Matrix Scaffolds

再生医学和个性化医学的融合有可能使治疗方法发生革命性变化 通过利用患者自身的免疫系统和 细胞外基质(ECM)支架实现组织修复。然而，在学术上取得的进展 研究转化为临床的速度很慢，很大程度上是因为无法制造这些 以标准化、可重复性和特定于患者的方式进行治疗。先进的制造技术 复杂的生物产品可以解决这个问题，成为这些新兴产品的使能技术 申请。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打印被证明具有更大的挑战性。在此，我们建议 开发将再生ECM支架转化为临床所需的关键新技术 满足ECM脚手架3D打印的关键制造需求。具体地说，我们已经在进程中确定了 监测、多尺度ECM支架制造和脱细胞ECM生物墨水是关键能力。去做 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。这项工作将 将进行的工作概括为三个具体目标。第一，设计集成3D生物打印和OCT 成像系统，可在生物制造过程中进行在线监控和实时反馈。这样做的目的是 目的是在3D生物打印过程中实现ECM支架的非破坏性3D成像，以便 快速评估成功/失败。二、开发多规模生物制造工艺，可将多种 3D打印方法在单个构造中概括了自然组织的组成和结构。的目标是 这一目标是为了解决构建大体积ECM支架的挑战，这种支架也需要纳米到微米级的 尺度分辨率以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。这个 这一目标的目标是将我们现有的用于容积性肌肉修复的再生ECM支架从 将手工制造过程转变为自动化、先进的制造过程，并使用CT和MRI成像 与患者特定组织缺陷相匹配的数据。这将产生深远的后果，导致 组织再生和发展先进制造业的临床相关治疗策略 实现产业规模扩大和翻译所需的能力。

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.