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

该提案的目的是开发新的电纺丝技术和方法，以创建具有成本效益的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，以确保可重现的细胞培养条件。然而，这些平台缺乏存在于天然组织微环境内的形貌、物理结构，限制了它们与临床应用的相关性。该研究小组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2微米或更小的聚合物纤维组成。来自身体所有组织的细胞容易识别纤维支架并利用其结构进行附着、迁移和定向延伸，这产生了比标准培养平台实现的更类似于天然组织中发现的那些的形态。静电纺丝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而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。该提案的目标是使制造过程自动化并扩大生产，同时保持对纤维性质的严格控制，以便将电纺纤维支架作为消费性研究工具商业化。实施计算机辅助制造系统将提供必要的精度和控制制造这些微尺度的功能scaffolds.The当前的范式为任何特定疾病的药物治疗的发展开始在基础科学实验室，化学化合物进行筛选细胞培养所需的效果。这个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，这为更复杂的动物模型让路。不幸的是，这个过程的成功结果非常少，成本很高，即使在进入市场后也会出现无数意想不到的副作用。本文所述的建议旨在启动这一有缺陷的系统的转型。电纺纤维培养支架在体外模拟组织结构，提供更复杂的细胞培养数据，以加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递送能力，它们还可以作为治疗本身。更早地为研究人员提供更多信息也可以减少动物试验，从而减少伦理问题并最大限度地减少产品开销。

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.