SBIR PHASE II, TOPIC 019: ELECTROSPUN BIODEGRADABLE MEMBRANE INSERTS

细胞培养工具扩展了我们进行研究的能力，从研究基本特性到开发特定的医学治疗。当这些工具尽可能接近地模拟细胞和组织的生物环境，同时在高通量体外分析中保持高再现性时，这些工具的效果最好。因此，细胞培养正在转向3D组织模型，专注于它们在体内的类似特性，而不是早期的2D培养。可生物降解的纳米纤维膜为体外组织建模提供了一个进步：它们包含仿生ECM地形，为新生组织提供临时的结构支持和相关的机械和空间生长线索。提出的细胞培养生物可降解插入膜将为种子细胞提供早期仿生支持；细胞外基质将在降解时取代膜的功能，从而形成附着在插入物上的独立组织，用于实验。为此，生物可降解膜将被纳入一个新的细胞培养插入96孔板。静电纺丝将用于制备由PCL和PLGA这两种具有良好表征的可生物降解生物材料组成的纳米纤维膜。两种设计将首先用单培养细胞片进行研究，然后在第一阶段的神经元共培养模型中验证插入物。插入物需要具有特定的尺寸，与大多数研究人员使用的成像技术兼容，并且具有特定的孔径和降解动力学，以模拟与体内的整合。

Cell culture tools expand our abilities to conduct research from studying basic properties to developing specific medical treatments. These tools work best when they mimic cell’s and tissue's biological environment as closely as possible while maintaining high reproducibility in high throughput in vitro assays. As such, cell culture is moving to 3D tissue models, focusing on their in vivo-like properties as opposed to earlier 2D culture. Biodegradable nanofiber membranes offer an advance for in vitro tissue modeling: they contain biomimetic ECM topography, which provides temporary structural support and relevant mechanical and spatial growth cues for nascent tissues. The proposed cell culture biodegradable insert membrane will provide early biomimetic support for seeded cells; cellular extracellular matrix will then replace the function of the membrane as is degrades, resulting in free-standing tissue attached to the insert, for experimentation. To this end, biodegradable membranes will be incorporated into a novel cell culture insert for 96-well plates. Electrospinning will be used to create the nanofibrillar membranes composed of PCL and PLGA, two well characterized biodegradable biomaterials. Two designs will be investigated initially with monoculture cell sheets, and then subsequently, in the Phase I neuronal co-culture model to validate the insert. The insert is required to have specific dimensions, be compatible with imaging techniques used by most researchers, and to have specific pore size and degradation kinetics to mimic integration into the body.