Claisen and Mitsunobu functional graphenic materials as stem cell instructive 3D printed scaffolds for bone regeneration

Claisen 和 Mitsunobu 功能性石墨烯材料作为干细胞指导性 3D 打印支架用于骨再生

• 批准号: 1905665
• 负责人: Stefanie Sydlik
• 金额: $ 52.76万
• 依托单位: Carnegie-Mellon University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1905665&HistoricalAwards=false
• 关键词: Claisen; Mitsunobu; functional; graphenic; materials

Non-technical Abstract:This project aims to develop a resorbable scaffold that supports the bone regrowth after injury. Stem cells hold great promise to enable bone regrowth, but current scaffolds lack the ability to retain and provide signals to stem cells to enable their transformation into bone-forming cells at the site of injury. To overcome these limitations, functional graphenic materials (FGMs) hold promise. Graphite is abundantly available and can be chemically modified to form FGMs. FGMs offer excellent and tunable mechanical properties, degradability, and controllable surface chemistry that can be translated to tunable bioactivity. However, this is not yet possible because a suitable processing method does not exist. Here, the PI will develop new FGMs with the ability to retain and direct the healing response of bone-forming cells. Further, the PI will develop 3D printing methods for these FGMs to create personalized scaffolds for patients. Ultimately, FGMs could replace permanent hardware used in the surgical treatment of traumatic bone injury with a resorbable material that allows regeneration of natural bone. Beyond societal impacts, undergraduate and graduate students will be trained in the classroom and laboratory, as well as perform outreach activities to empower and engage women and underrepresented populations.Technical Abstract:This project aims to develop novel methods to synthesize and 3D print biomimetic, functional graphene materials (FGMs) that will serve as scaffolds for instructed stem cell regeneration of bone. Current methods for stem cell driven regeneration are limited because a scaffold that recruits stem cells and supports their retention as they differentiate into functional tissue. FGMs offer a unique panel of properties not found in any other single material and therefore has the potential to overcome these limitations. Specifically, FGMs offer autodegradability, mechanical properties, and long range order, coupled with controllable surface chemistry. Graphene oxide (GO) offers a plethora of organic functionality that can be used to tune the surface chemistry to maximize cellular interactions biocompatibility in FGMs. However, realization of these properties has been limited due to insufficient control of the chemical interface, and applications have been limited by an inability to produce a robust 3D scaffold. Here, new methods will be developed to create biomimetic FGMs by using the Claisen rearrangement and the Mitsunobu reaction: classic organic reactions to covalently install biomimetic moieties directly at the surface of the biomaterial. At the end of this funding period, the project will: 1) Demonstrate the ability of Claisen Graphene, CG, to create an instructive surface to promote superior stem cell adhesion. 2) Demonstrate superior stability of proteins, directed stem cell differentiation, and covalent controlled release using Mitsunobu Graphene, MG. 3) Innovate 3DP methods to produce FGM scaffolds suitable for implantation in vivo. Overall, this work on bone will provide valuable insights on stem cell directing therapies and could unlock the potential of stem cell directed regeneration in a plethora of tissue engineering therapies. Beyond societal impacts, this project supports ChemCast, a podcast designed to keep students up to date on research topics as well as outreach activities including the "Chemistry of Cycling".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.

非技术摘要：本项目旨在开发一种可吸收支架，用于支持损伤后的骨再生。干细胞有很大的希望使骨再生，但目前的支架缺乏保留和提供信号给干细胞，使其转化为骨形成细胞在损伤部位的能力。为了克服这些限制，功能性石墨烯材料（FGM）有希望。石墨是大量可获得的，并且可以被化学改性以形成FGM。FGM提供优异且可调的机械性能、降解性和可控的表面化学，其可以转化为可调的生物活性。然而，这是不可能的，因为不存在合适的处理方法。在这里，PI将开发新的FGM，具有保留和指导骨形成细胞愈合反应的能力。此外，PI将为这些FGM开发3D打印方法，为患者创建个性化支架。最终，FGM可以用可吸收的材料代替用于创伤性骨损伤手术治疗的永久性硬件，该材料允许天然骨再生。除了社会影响，本科生和研究生将在课堂和实验室接受培训，并开展外展活动，以增强妇女和代表性不足的人群的权能和参与。技术摘要：该项目旨在开发合成和3D打印仿生功能石墨烯材料（FGM）的新方法，这些材料将作为指导性干细胞骨再生的支架。目前用于干细胞驱动再生的方法是有限的，因为支架招募干细胞并在它们分化成功能组织时支持它们的保留。功能梯度材料提供了在任何其他单一材料中找不到的独特性能，因此有可能克服这些限制。具体而言，FGM提供自动降解性、机械性能和长程有序性，以及可控的表面化学。氧化石墨烯（GO）提供了大量的有机官能团，其可用于调节表面化学以最大化FGM中的细胞相互作用生物相容性。然而，由于对化学界面的控制不足，这些特性的实现受到限制，并且应用受到无法产生坚固的3D支架的限制。在这里，将开发新的方法来创建仿生FGM通过使用克莱森重排和Mitsunobu反应：经典的有机反应，直接在生物材料的表面共价安装仿生部分。在本资助期结束时，该项目将：1）证明Claisen Graphene，CG，创造一个指导性表面，以促进上级干细胞粘附的能力。2)使用Mitsunobu Graphene，MG证明蛋白质的上级稳定性、定向干细胞分化和共价控制释放。3)创新3DP方法，生产适合体内植入的FGM支架。总的来说，这项关于骨的工作将为干细胞定向治疗提供有价值的见解，并可能在大量的组织工程治疗中释放干细胞定向再生的潜力。除了社会影响，该项目还支持ChemCast，这是一个播客，旨在让学生了解最新的研究课题以及包括“自行车化学”在内的外联活动。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

项目成果

Hands-On Laboratory Experience Using Adhesives for Remote Learning of Polymer Chemistry

• DOI: 10.1021/acs.jchemed.0c01374
• 发表时间: 2021-09-20
• 期刊: JOURNAL OF CHEMICAL EDUCATION
• 影响因子: 3
• 作者: Schmidt，S.;Wright，Z. M.;Sydlik，S. A.
• 通讯作者: Sydlik，S. A.