I-Corps: Production Scale-up of Electrospun Fiber Scaffolds as Research Tools

I-Corps：作为研究工具的静电纺纤维支架的生产规模扩大

• 批准号: 1358895
• 负责人: Ryan Gilbert
• 金额: $ 5万
• 依托单位: Rensselaer Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1358895&HistoricalAwards=false
• 关键词: Corps; Production; Scale; up; Electrospun

The purpose of this proposal is to develop new electrospinning technologies and methodologies to create cost efficient electrospinning materials as cell culture platforms. Standard cell culture platforms are disposable, plastic dishes or wellplates with tightly controlled properties to ensure reproducible cell culture conditions. However, these platforms lack topographical, physical structures that are present within the native tissue microenvironment, limiting their relevance to clinical applications. The research team strives to attenuate the disparity between cell culture platforms and biological tissues by use of electrospun fiber scaffolds. These scaffolds are composed of polymeric fibers only two microns or less in diameter. Cells from all tissues of the body readily recognize the fibrous scaffold and utilize its structure for attachment, migration, and directed elongation, which produces morphologies more similar to those found in native tissues than standard culture platforms achieve. Electrospun fibers are commonly fabricated for intra-laboratory use, but lack the potential for widespread dissemination due to an inefficient fabrication process. Production is labor intensive and requires a skilled technician for fabrication and characterization. The goal for this proposal is to automate the manufacturing process and scale up production while retaining tight control over the fiber properties in order to commercialize electrospun fiber scaffolds as a consumable research tool. Implementing computer-aided manufacturing systems will provide the necessary precision and control for fabrication of these microscale-featured scaffolds.The current paradigm for development of pharmacological therapies to any particular disease begins in the basic science laboratory where chemical compounds are screened against cell cultures for a desired effect. This screening process is a prelude to rodent studies that test safety and efficacy, which gives way to more complex animal models before human clinical trials. Unfortunately, the number of successful outcomes from this process is quite low, it is costly, and there are countless incidences of unanticipated side effects even after reaching the marketplace. The proposal described herein is set to initiate transformation of this flawed system. Electrospun fiber culture scaffolds emulate tissue architecture in vitro, providing more sophisticated cell culture data to enhance the screening process in the earliest stages. The role of the fibers is not limited to only a research tool, but they can also serve as the therapy itself given their unique physical properties and controlled compound delivery capabilities. Providing researchers with more information earlier can also lead to a reduction in animal testing, which reduces ethical concerns and minimizes product overhead.

该提案的目的是开发新的静电纺丝技术和方法，以创建具有成本效益的静电纺丝材料作为细胞培养平台。标准细胞培养平台是一次性塑料培养皿或孔板，具有严格控制的特性，以确保可重复的细胞培养条件。然而，这些平台缺乏天然组织微环境中存在的地形、物理结构，限制了它们与临床应用的相关性。研究团队致力于通过使用电纺纤维支架来缩小细胞培养平台和生物组织之间的差异。这些支架由直径仅为两微米或更小的聚合物纤维组成。来自身体所有组织的细胞很容易识别纤维支架，并利用其结构进行附着、迁移和定向伸长，这产生的形态比标准培养平台所实现的形态更类似于天然组织中发现的形态。电纺纤维通常被制造用于实验室内使用，但由于制造过程效率低下，缺乏广泛传播的潜力。生产是劳动密集型的，需要熟练的技术人员进行制造和表征。该提案的目标是实现制造过程自动化并扩大生产规模，同时保持对纤维性能的严格控制，以便将电纺纤维支架作为消耗性研究工具商业化。实施计算机辅助制造系统将为制造这些微型特征支架提供必要的精度和控制。针对任何特定疾病的药物疗法的当前开发范例始于基础科学实验室，在该实验室中根据细胞培养物筛选化合物以获得所需的效果。这一筛选过程是测试安全性和有效性的啮齿动物研究的前奏，在人体临床试验之前为更复杂的动物模型让路。不幸的是，这个过程的成功率非常低，成本高昂，而且即使在进入市场后也会出现无数意想不到的副作用。本文描述的提案旨在启动对这个有缺陷的系统的改造。电纺纤维培养支架模拟体外组织结构，提供更复杂的细胞培养数据，以增强最早阶段的筛选过程。纤维的作用不仅限于研究工具，而且由于其独特的物理特性和受控的化合物输送能力，它们本身也可以用作治疗方法。尽早向研究人员提供更多信息还可以减少动物测试，从而减少道德问题并最大限度地减少产品开销。