CAREER: Graphene as a Bioscaffold for Musculoskeletal Tissue Engineering

技术摘要：美国国家科学基金会职业奖的目的是通过使用新方法研究石墨烯等原子薄材料在控制干细胞命运方面的新兴作用，丰富对干细胞生物学基本原理的科学理解。为了实现这一目标，首席研究员将把石墨烯和石墨烯衍生物的功能模式整合到生物支架中，以控制和测量人类间充质干细胞（hMSC）生长和分化的基本生物物理信号。石墨烯生物支架的电连接将用于调节温度和电场，同时还可以主动监测细胞-石墨烯界面在生长和分化过程中的电化学交换。为了阐明石墨烯的结构-性能-加工与hMSC分化的相关性，将比较在SiC衬底上外延石墨烯上生长hMSC、在铜箔上化学气相沉积生长多晶石墨烯薄膜以及在化学剥落的石墨烯纳米片上印刷的石墨烯薄膜的遗传谱。施加在石墨烯薄膜上的电偏压将用于监测跨膜电压对hMSC命运的影响，以及电信号对细胞外基质产生和工程肌肉骨骼组织机械性能的影响。智力优势：获得的基础知识将使电活性生物支架的一套完整的设计规则能够耦合或解耦负责干细胞生长和分化的生物物理线索。通过这些实验产生的数据将公开提供，以进一步推进生物分子过程的计算机研究，并随后整合到虚拟生理人体模型中。更广泛的影响：通过将石墨烯整合到组织工程周期中，潜在的转变结果可能包括干细胞培养的新仪器，新的多功能生物支架材料，以及组织工程和再生医学的新研究途径。综合教育推广活动利用当地双语浸入式公立特许学校和本科服务学习计划，提高英语学习者对STEM机会的认识。干细胞提供了发展成许多不同细胞类型和组织的非凡能力。因此，它们不仅具有治愈受损或患病器官的潜力，而且还为研究生命的基本化学提供了一个平台。长期以来，研究人员一直在体外研究干细胞生物学，重点关注生化反应和机械因素对干细胞命运的影响。这些科学家在作为生物支架的各种材料上培养干细胞，设计这些材料来利用干细胞和支架之间的机械串扰来控制它们的命运。很少有研究利用在空间和时间上变化的电和热信号来控制干细胞的命运。最近发现的石墨烯（单层碳原子排列成二维六边形晶体结构）为生物支架控制与干细胞的电和热相互作用开辟了新的可能性。因此，NSF CAREER奖的目标是将石墨烯与干细胞生物学结合起来，揭示这两个系统的基本相互作用。这项工作将对干细胞生物学和原子薄材料的研究产生影响，为控制干细胞命运的电和热线索的作用提供新的基本见解。更广泛的影响：实现对干细胞命运的控制可以彻底改变组织工程和再生医学，减少对器官供体的依赖来治疗终末期器官衰竭患者。科学推广活动将有助于建立一个管道，让英语学习者从当地的双语浸入式课程进入博伊西州立大学的STEM课程。该奖项反映了美国国家科学基金会的法定使命，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。

TECHNICAL ABSTRACTThe purpose of this NSF CAREER Award is to enrich scientific understanding of basic principles governing stem cell biology by using novel approaches to investigate the emerging role of atomically thin materials such as graphene in controlling stem cell fate. To accomplish this, the principle investigator will integrate functionally patterned graphene and graphene derivatives into bioscaffolds to control and measure the fundamental biophysical cues that encode information for human mesenchymal stem cell (hMSC) growth and differentiation. Electrical connections to the graphene bioscaffolds will serve to modulate temperature and electrical fields while also actively monitoring the electrochemical exchange at the cell-graphene interface during growth and differentiation. In order to elucidate graphene's structure-property-processing correlations on hMSC differentiation, genetic profiles will be compared for hMSC growth on epitaxial graphene on SiC substrates, polycrystalline graphene films grown by chemical vapor deposition on copper foils, and graphene films printed from chemically exfoliated graphene nanoflakes. Electrical bias applied to the graphene films will be used to monitor the effect of transmembrane voltage on hMSC fate, as well as the impact of electrical signals on extracellular matrix production and the mechanical properties of engineered musculoskeletal tissue. Intellectual Merit: The fundamental knowledge gained will enable a complete set of design rules for electrically active bioscaffolds that can couple or decouple biophysical cues responsible for stem cell growth and differentiation. The data produced through these experiments will be made publicly available to further advance in silico research of biomolecular processes and subsequent integration in virtual physiological human models. Broader Impacts: By integrating graphene into the tissue engineering cycle, potentially transformational outcomes will likely include new instrumentation for stem cell culture, new multifunctional bioscaffold materials, and new research avenues for tissue engineering and regenerative medicine. Integrated educational outreach activities leverage a local dual-language immersion public charter school and undergraduate service-learning programs to raise awareness about STEM opportunities for English language learners. NON-TECHNICAL ABSTRACTStem cells offer the remarkable ability to develop into many different cell types and tissues. Thus, they not only have the potential to cure damaged or diseased organs, but also provide a platform to study the fundamental chemistry of life. Researchers have long studied stem cell biology in vitro with a focus on the impact of biochemical reactions and mechanical cues on stem cell fate. These scientists culture stem cells on various types of materials which serve as bioscaffolds, engineering the materials to leverage the mechanical crosstalk between the stem cell and the scaffold to control their fate. There are few investigations that leverage electrical and thermal cues which vary in space and time to control stem cell fate. The recent discovery of graphene (a single layer of carbon atoms arranged in a 2-dimensional hexagonal crystal structure) has opened up new possibilities for bioscaffolds to control such electrical and thermal interactions with stem cells. Therefore, the goal of this NSF CAREER award is to integrate graphene with stem cell biology to uncover the fundamental interactions of these two systems. Intellectual Merit The proposed work will have an impact on stem cell biology and atomically thin materials research by providing new fundamental insights into the role of electrical and thermal cues in controlling stem cell fate. Broader Impacts: Achieving control over stem cell fate could revolutionize tissue engineering and regenerative medicine, reducing dependence on organ donors to treat patient end-stage organ failure. Scientific outreach activities will help establish a pipeline of English language learners from a local dual-language immersion program into Boise State University's STEM programs.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.