CAREER: Graphene as a Bioscaffold for Musculoskeletal Tissue Engineering

职业：石墨烯作为肌肉骨骼组织工程的生物支架

• 批准号: 1848516
• 负责人: David Estrada
• 金额: $ 55.08万
• 依托单位: Boise State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1848516&HistoricalAwards=false
• 关键词: CAREER; Graphene; Bioscaffold; Musculoskeletal; Tissue

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.

技术摘要该NSF职业奖的目的是通过使用新颖的方法来研究对干细胞生物学的基本原理的科学理解，以研究原子上稀薄材料（例如石墨烯）在控制干细胞命运中的新兴作用。为此，原理研究者将将功能上图案的石墨烯和石墨烯衍生物整合到生物遵循，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提示。与石墨烯生物遵循的电气连接将用于调节温度和电场，同时还可以在生长和分化过程中积极监测细胞 - 透明烯界面的电化学交换。为了阐明石墨烯在HMSC分化方面的结构 - 加工相关性，将比较SIC底物上外延长石墨烯的HMSC增长的遗传概况，通过铜箔上的化学蒸气沉积而生长的多晶石墨烯膜，在铜箔上的化学蒸气沉积，并从化学上剥皮的石墨烯层印刷的石墨烯膜。应用于石墨烯膜的电偏置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的影响以及工程肌肉骨骼组织的机械性能。知识分子的优点：获得的基本知识将为电活动的生物遵循的完整设计规则提供，这些设计规则可以使或解除负责干细胞生长和分化的生物物理提示。通过这些实验产生的数据将公开可用，以进一步促进生物分子过程的硅研究和随后在虚拟生理人类模型中的整合。更广泛的影响：通过将石墨烯整合到组织工程周期中，潜在的转化结果可能包括用于干细胞培养的新仪器，新的多功能生物遵循材料以及用于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了当地的双语言沉浸式公共特许学校和本科服务学习计划，以提高人们对英语学习者STEM机会的认识。非技术抽象系统细胞具有出色的能力，可以发展为许多不同的细胞类型和组织。因此，他们不仅有潜力治愈受损或患病的器官，而且还提供了研究生命基本化学的平台。长期以来，研究人员在体外研究了干细胞生物学，重点是生化反应和机械线索对干细胞命运的影响。这些科学家将干细胞培养在各种类型的材料上，这些材料用作生物施加剂，设计材料以利用干细胞和脚手架之间的机械串扰来控制其命运。很少有研究利用电气和热线索的空间和时间来控制干细胞命运。最近发现石墨烯（在二维六边形晶体结构中排列的碳原子的单层）为Bioscaffolds控制了与干细胞的这种电和热相互作用开辟了新的可能性。因此，该NSF职业奖的目标是将石墨烯与干细胞生物学整合在一起，以揭示这两个系统的基本相互作用。智力优点该提议的工作将通过提供对电气和热线索在控制干细胞命运中的作用的新基本见解，对干细胞生物学和原子薄材料研究产生影响。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，从而减少对器官捐献者的依赖，以治疗患者终端器官衰竭。科学外展活动将有助于从当地的双语言沉浸式计划中建立英语学习者的管道。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子的评估来支持的，并具有更广泛的影响。

项目成果

Prechondrogenic ATDC5 Cell Attachment and Differentiation on Graphene Foam; Modulation by Surface Functionalization with Fibronectin

• DOI: 10.1021/acsami.9b14670
• 发表时间: 2019-11-13
• 期刊: ACS APPLIED MATERIALS & INTERFACES
• 影响因子: 9.5
• 作者: Frahs, Stephanie M.;Reeck, Jonathon C.;Oxford, Julia Thom
• 通讯作者: Oxford, Julia Thom

Differential Gene Expression in C2C12 Cells due to Scaffold Structure-Property-Processing-Performance Correlations

由于支架结构-性质-加工-性能相关性导致 C2C12 细胞中基因表达差异

• 发表时间: 2021
• 期刊: 63rd Electronic Materials Conference (EMC 2021
• 作者: Karriem, L. Frahs