CAREER: Graphene as a Bioscaffold for Musculoskeletal Tissue Engineering

NSF职业奖的目的是通过使用新的方法来研究原子薄材料(如石墨烯)在控制干细胞命运中的新兴作用，从而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，首席研究员将把功能图案化的石墨烯和石墨烯衍生物集成到生物支架中，以控制和测量基本的生物物理线索，这些线索编码了人类间充质干细胞(HMSC)生长和分化的信息。与石墨烯生物支架的电连接将用于调节温度和电场，同时还可以积极监测细胞-石墨烯界面在生长和分化过程中的电化学交换。为了阐明石墨烯在hMSC分化中的结构-性质-加工关系，我们将比较在碳化硅衬底上外延石墨烯上生长的hMSC、在铜箔上化学气相沉积生长的多晶石墨烯薄膜以及由化学剥离的石墨烯纳米片印刷的石墨烯薄膜。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化肌肉骨骼组织机械性能的影响。智力价值：所获得的基础知识将使一套完整的电活性生物支架设计规则成为可能，这些规则可以结合或分离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被公开，以进一步推进生物分子过程的电子研究以及随后在虚拟生理人体模型中的集成。更广泛的影响：通过将石墨烯整合到组织工程周期中，潜在的变革性成果可能包括用于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。综合教育外展活动利用当地的双语浸入式公共特许学校和本科服务学习计划，提高对STEM机会的认识，为英语语言学习者提供机会。非技术性干细胞提供了发育成多种不同细胞类型和组织的非凡能力。因此，它们不仅有可能治愈受损或患病的器官，而且还提供了一个研究生命基本化学的平台。长期以来，研究人员一直在体外研究干细胞生物学，重点是生化反应和机械信号对干细胞命运的影响。这些科学家在用作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不同的电和热线索来控制干细胞的命运。最近石墨烯(以二维六方晶体结构排列的单层碳原子)的发现为生物支架控制与干细胞的这种电和热相互作用开辟了新的可能性。因此，NSF职业奖的目标是将石墨烯与干细胞生物学相结合，以揭示这两个系统的基本相互作用。智力价值拟议的工作将对干细胞生物学和原子薄材料研究产生影响，为电和热信号在控制干细胞命运中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能会给组织工程和再生医学带来革命性的变化，减少对器官捐赠者治疗患者终末期器官衰竭的依赖。科学推广活动将帮助建立一个渠道，英语学习者从当地的双语沉浸项目进入博伊西州立大学的STEM项目。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.