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

这项提议的目的是开发新的电纺丝技术和方法，以创造成本效益高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井板，其性能受到严格控制，以确保细胞培养条件可重现。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。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距。这些支架由直径只有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、迁移和定向延伸，从而产生比标准培养平台更类似于自然组织中的形态。电纺纤维通常在实验室内使用，但由于制造工艺效率低下，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来制造和表征。这项提议的目标是使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进行商业化。实施计算机辅助制造系统将为制造这些具有微尺度特征的支架提供必要的精度和控制。目前开发针对任何特定疾病的药物疗法的范例始于基础科学实验室，在那里，化合物被与细胞培养进行筛选，以获得预期的效果。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，在人类临床试验之前，啮齿动物研究让位于更复杂的动物模型。不幸的是，这一过程的成功结果数量相当少，成本很高，而且即使在上市后也会出现无数意想不到的副作用。这里描述的提议旨在启动对该有缺陷的系统的改造。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，以加强早期阶段的筛选过程。纤维的作用不仅限于一种研究工具，而且由于其独特的物理特性和受控的化合物输送能力，它们还可以用作治疗本身。更早地向研究人员提供更多信息也可以减少动物试验，这减少了伦理担忧，并将产品管理费用降至最低。

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.