Microengineered Bioactive Fibers for Fabrication of Vascularized Tissues

组织工程是一个多学科领域，汇集了工程，生物学，医学和化学背景的研究人员，以建立组织样结构，用于进行基础生物学研究和预测新的和现有药物的过敏或毒性潜力。随着生物制造技术的出现，如静电纺丝，光图案化和立体光刻，已经出现了令人兴奋的机会，用于创建可以为细胞生长和功能提供结构的支架。然而，对支架的机械性能、细胞分布和微结构的控制仍然是一个关键的挑战，特别是对于具有高度各向异性特性的组织，如心脏组织、骨骼肌和外周神经。该项目的总体目标是开发一种“自下而上”的方法，其中具有不同细胞，化学和物理特性的纤维模块将在微流体环境中制造（目标1），然后使用纺织技术（如编织，编织和刺绣）组装成更高阶的结构（目标2）。使用纤维状几何形状的主要理由是，它复制了心血管系统的巨大小管网络以及肌肉骨骼和外周神经系统的纤维结构。到目前为止，还没有技术能够创造出能够模仿这些复杂组织的复杂性的支架。此外，所提出的平台将用于构建工程化血管化组织，以研究体外细胞-细胞相互作用和血管网络形成（目标3）。总的来说，这一建议的结果将为理解几个主要的生物学问题铺平道路，包括：1）确定纤维状结构的物理化学性质对细胞生长和功能的影响; 2）研究生长因子对以空间可控方式调节周围细胞功能的影响;以及3）研究功能和支持细胞类型的特定排列、可溶性或不溶性因子的梯度对组织功能的影响。* 根据本研究计划培训的高素质人员（HQP）预计将在机械工程，生物材料和生物学领域发展多学科技能，并获得尖端技术的宝贵实践经验。来自我们小组的训练有素的HQP将拥有CAD建模，有限元分析（FEA），微加工，生物材料合成和细胞培养等方面的技能。此外，HQP将享受丰富的沟通和人际交往的锻炼，他们的计划结束。这种技能的结合将有助于我们训练有素的HQP在学院或工业研发部门追求职业生涯。**

Tissue engineering is a multidisciplinary field that brings together researchers with backgrounds in engineering, biology, medicine, and chemistry to build tissue-like constructs for performing fundamental biological studies and predicting the allergenic or toxic potentials of novel and existing drugs. With the advent of biofabrication techniques such as electrospinning, photo patterning, and stereolithography, exciting opportunities have emerged for creating scaffolds that can provide a structure for the cells to grow and function. However, control over the mechanical properties, cellular distribution, and microarchitecture of the scaffolds still remains a critical challenge, especially for tissues with highly anisotropic properties such as cardiac tissue, skeletal muscles, and peripheral nerves.***The overarching goal of this project is to develop a “bottom-up” approach, in which modules of fibers with different cellular, chemical, and physical properties will be fabricated in a microfluidic setting (Objective 1) and then assembled into higher order constructs using textile technologies such as weaving, braiding, and embroidering (Objective 2). The main rationale behind using fiber-shaped geometry is that it replicates the immense tubule network of the cardiovascular system and fibrous constructs of the musculoskeletal and peripheral nerve systems. To date, there is no technology capable of creating scaffolds that can imitate the complexities of these complex tissues. In addition, proposed platform will be used to fabricate engineered vascularized tissues to study the cell-cell interactions and vascular network formation in vitro (Objective 3).***Collectively, the outcomes of this proposal will pave the path towards understanding several principle biological questions including: 1) determining the impact of physicochemical properties of fiber-shaped constructs on cellular growth and function; 2) investigating the influence of growth factors on modulating the function of surrounding cells in a spatially controllable manner; and 3) investigating the effect of specific arrangement of functional and supporting cell types, gradients of soluble or insoluble factors on the tissue function. ****The highly qualified personnel (HQP) trained under this research program is expected to develop multidisciplinary skills in the fields of mechanical engineering, biomaterials and biology, and to gain valuable hands-on experience in cutting-edge techniques. The trained HQP from my group will possess skills in CAD modelling, Finite Element Analysis (FEA), microfabrication, biomaterial synthesis, and cell culture, among others. Additionally, the HQP will enjoy of plenty communication and interpersonal exercise by the end of their programs. This combination of skills will facilitate our trained HQP to pursue a career in academy or in the industrial R&D sector.**