CREST-Postdoctoral Research Fellowship: Extrusion Printing of Biomimetic Scaffolds for In Vitro Investigation of Tissue Regeneration in Multicellular Environments

卓越研究中心在科学和技术博士后研究奖学金（CREST-PRF）的CREST计划内的轨道支持开始CREST中心研究人员具有显着的潜力，并为他们提供培训和研究经验，将拓宽视野，促进跨学科的互动，并建立他们在科学界的领导地位。该CREST-PRF项目与佛罗里达农业与机械大学（FAMU）的CREST多维增材加工复杂材料设计中心（CoManD）的研究重点保持一致。这项研究的目标是使用3D打印矩阵在模拟自然环境的环境中研究细胞。利用FAMU和哈佛大学的技术，这项研究将允许在受控环境中研究细胞。研究技术和成果将用于创建FAMU工程课程的课程模块。 这项工作将使研究人员为独立的研究生涯奠定基础。更大的社区将通过在初中和高中的示威活动受到影响，使学生参与社区。组织再生/修复通常涉及多种细胞类型与不同特征的细胞外基质（ECM）的相互作用。 这是肌腱修复的情况，其中肌腱-骨界面由从韧带中对齐的纤维到骨中随机取向的过渡组成。 挤出打印水凝胶支架允许在一个支架中实现孔径、模量甚至组成梯度，以创建在体内看到的复杂细胞环境。 因此，这项工作的目标是利用挤出打印的多功能性来探测复杂多细胞界面处的组织再生。 使用具有新型微流体改性打印头和安装的UV灯的3D生物打印机，将打印水凝胶支架用于组织再生。 这项工作将集中在肌腱到骨的多细胞过渡，证明可调的结构，机械和生物化学特性的打印支架。 挤出打印和细胞研究将为复杂基质中的细胞行为提供新的见解。 通过在3D矩阵中研究该系统，我们将能够在与天然细胞外基质更相似的环境中探测细胞增殖，迁移和活力。此外，通过结合共焦拉曼光谱和微流控技术，这项工作将调查和随后调整矩阵刚度，各向异性和渗透性，以有效地研究细胞的生长和迁移与控制的物理和生化线索。这项工作将作为一个模型系统，用于各种组织/器官，这些组织/器官需要对细胞、营养物质或生长因子进行空间调节，以实现有效的再生。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The Centers of Research Excellence in Science and Technology-Postdoctoral Research Fellowship (CREST-PRF) track within the CREST program supports beginning CREST Center investigators with significant potential and provides them with training and research experiences that will broaden perspectives, facilitate interdisciplinary interactions and establish them in positions of leadership within the scientific community. This CREST-PRF project is aligned with the research focus of the CREST Center for Complex Materials Design for Multidimensional Additive Processing (CoManD) at Florida Agricultural and Mechanical University (FAMU). The goal of this research is to use 3D printed matrixes to study cells in an environment that mimics a natural environment. Using techniques at FAMU and Harvard University, the research will allow a study of cells in a controlled environment. Research techniques and results will be used to create course modules in engineering courses at FAMU. The work will allow the researcher to build a foundation for an independent research career. The larger community will be impacted through demonstrations at middle and high schools to engage students in the community. Tissue regeneration/repair can often involve the interaction of multiple cell types with different characteristic extracellular matrices (ECM). Such is the case for tendon repair where the tendon-to-bone interface is composed of a transition from aligned fibers in the ligaments to randomly oriented in the bone. Extrusion printing hydrogel scaffolds allows the implementation of pore size, modulus, and even compositional gradients all in one scaffold to create complex cellular environments seen in the body. Consequently, the goal of this work is to use the versatility of extrusion printing to probe tissue regeneration at complex multicellular interfaces. Using a 3D bio printer with a novel microfluidic modified print head and mounted UV lamp, hydrogel scaffolds will be printed for tissue regeneration. This work will focus on the tendon-to-bone multicellular transition demonstrating tunable structural, mechanical, and biochemical properties in a printed scaffold. Extrusion printing and cell studies will present new insights into cell behavior in a complex matrix. By studying this system in a 3D matrix we will be able to probe cell proliferation, migration, and viability in an environment with a closer resemblance to the native extracellular matrix. In addition, through the combination of confocal Raman spectroscopy and the microfluidic technique, this work will investigate and subsequently tune matrix stiffness, anisotropy, and permeability in order to effectively study growth and migration of cells with controlled physical and biochemical cues. The proposed work will serve as a model system for a variety of tissues/organs that require the spatial regulation of cells, nutrients, or growth factors for effective regeneration.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.