Nanomanufacturing of Biopolymer Nanofiber Hierarchical Assemblies

直接细胞环境，通常称为细胞外基质，由微/纳米纤维（直径：微米至100纳米以下）组成，并作为支架，体内大多数细胞附着在其上并接受机械和化学提示。随着对细胞外基质-细胞相互作用中的对齐作用以及生物物理学线索在发育和疾病模型（包括癌症）中的作用的认识不断提高，有必要开发模拟天然环境的纤维制造技术，用于体内翻译和体外细胞行为研究。静电纺丝是制造纳米纤维最常用的制造方法。然而，它仍然缺乏对纤维直径、间距和取向的精确控制。该奖项利用非静电纺丝纤维制造平台，通过改善生物聚合物的可纺性，控制多层纤维直径，间距和方向，为细胞研究构建精确的生物物理环境。所得到的构建体可以有助于开发用于组织工程的可植入支架和单细胞诊断平台。因此，这项研究的成果将有利于美国的经济和社会。这项多学科研究涉及制造、聚合物物理、生物、力学和机械工程等学科的元素。该奖项将有助于扩大工程研究中代表性不足的群体的参与，并对本科和研究生阶段的工程教育产生积极影响。纳米级聚合物纤维形成的物理学涉及溶液流变学和外加外力之间的微妙平衡，这使得纳米制造和纳米纤维的分级组装极具挑战性。为了增强我们在纤维制造方面的能力，本工作将使用非静电纺丝的纤维制造平台来研究纤维的可纺性。由于在制造过程中消除了电源，该平台将提供对纤维直径、取向、间距和组装的上级控制，特别是在多层中。使用聚（乳酸-共-乙交酯酸）和纤维蛋白原作为模型聚合物系统，该项目将开发纤维可纺性标度律，代表跨越广泛的溶液流变学和加工参数的纤维直径设计空间。此外，使用原子力显微镜在不同应变率下对单根纤维进行机械拉伸测试，将提供制造过程中纤维失效概率的威布尔分布。这项研究将填补生物聚合物可纺性的知识空白，并首次提供制造代表生物物理线索梯度的定制架构的能力。因此，整个研究将提供一个路线图，以设计和构建具有更高质量，可扩展性和可重复性的生物聚合物支架。

Immediate cellular environment, commonly referred to as the extracellular matrix, consists of micro/nanofibers (diameter: microns to sub-100 nanometers) and serves as a scaffold upon which most cells in the body attach and receive mechanical and chemical cues. An increased awareness of the role of alignment in extracellular matrix-cell interactions and the role of biophysical cues in development and disease models including cancer has necessitated the development of fiber manufacturing technologies mimicking the native environments for in vivo translational and in vitro cell behavior studies. Electrospinning is the most commonly used manufacturing method to fabricate nanofibers. However, it still lacks precise control on fiber diameter, spacing and orientation. This award utilizes a non-electrospinning fiber manufacturing platform to architect precise biophysical environments for cell studies through improved spinnability of biopolymers with control on fiber diameter, spacing and orientation in multiple layers. The resulting constructs can be instrumental in developing implantable scaffolds for tissue engineering, and single cell diagnostic platforms. Therefore, results from this research will benefit the U.S. economy and society. This multidisciplinary research involves elements from disciplines such as manufacturing, polymer physics, biology, mechanics and mechanical engineering. The award will help broaden participation of underrepresented groups in engineering research and positively impact engineering education at both undergraduate and graduate levels.The physics of polymer fiber formation at the nanoscale involves a delicate balance between solution rheology and applied external forces, which makes nanomanufacturing and hierarchical assembly of nanofibers extremely challenging. To augment our capabilities in fiber manufacturing, a non-electrospinning nanofiber manufacturing platform will be used to study fiber spinnability in this work. Due to elimination of electric source in the manufacturing process, the platform will provide superior control on fiber diameter, orientation, spacing and assembly, particularly in multiple layers. Using poly (lactic-co-glycolide acid) and fibrinogen as model polymer systems, this project will develop fiber spinnability scaling laws representing fiber diameter design space spanning a wide range of solution rheologies and processing parameters. Furthermore, mechanical tensile testing of single fibers using atomic force microscopy at different strain rates will provide the fiber probability failure Weibull distributions in the manufacturing process. This research will fill the knowledge gap on the spinnability of biopolymers and for the first time provide the ability to manufacture custom architectures representing gradients in biophysical cues. The overall research will thus provide a roadmap to design and build scaffolds of biopolymers with improved quality, scalability and repeatability.