CAREER: Graphene as a Bioscaffold for Musculoskeletal Tissue Engineering

技术摘要这个NSF职业奖的目的是通过使用新的方法来研究原子级薄材料如石墨烯在控制干细胞命运中的新兴作用，从而丰富对管理干细胞生物学的基本原理的科学理解。为了实现这一目标，主要研究人员将功能图案化的石墨烯和石墨烯衍生物整合到生物支架中，以控制和测量编码人类间充质干细胞（hMSC）生长和分化信息的基本生物物理线索。与石墨烯生物支架的电连接将用于调节温度和电场，同时还在生长和分化期间主动监测细胞-石墨烯界面处的电化学交换。为了阐明石墨烯在hMSC分化上的结构-性质-加工相关性，将比较hMSC在SiC衬底上的外延石墨烯上的生长、通过化学气相沉积在铜箔上生长的多晶石墨烯膜和从化学剥离的石墨烯纳米片印刷的石墨烯膜的遗传谱。施加到石墨烯膜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的机械性能的影响。智力优势：所获得的基本知识将使一套完整的设计规则的电活性生物支架，可以耦合或解耦生物物理线索负责干细胞的生长和分化。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沉浸式公立特许学校和本科服务学习计划，以提高英语学习者对STEM机会的认识。非技术摘要干细胞提供了发育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，而且还提供了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线索对干细胞命运的影响。这些科学家在各种类型的材料上培养干细胞，这些材料用作生物支架，工程材料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线索来控制干细胞的命运。最近发现的石墨烯（单层碳原子排列在二维六边形晶体结构中）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，这个NSF CAREER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。这项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能会彻底改变组织工程和再生医学，减少对器官捐赠者的依赖，以治疗患者的终末期器官衰竭。科学推广活动将有助于建立一个管道的英语学习者从当地的双语浸入式课程到博伊西州立大学的STEM课程。这个奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

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.