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

基本信息

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

项目摘要

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：该项目旨在开发可吸收脚手架，该支架支持受伤后的骨骼再生。干细胞具有巨大的希望，可以使骨骼再生，但是当前的支架缺乏保留的能力，并提供信号以使其能够在损伤部位转化为骨形成细胞。为了克服这些局限性，功能性石墨材料（FGM）保持了承诺。石墨可用，可以化学修改以形成FGM。 FGM具有出色且可调的机械性能，可降解性和可控制的表面化学性质，可以转化为可调生物活性。但是，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的愈合反应的能力。此外，PI将为这些FGM开发3D打印方法，以为患者创建个性化的脚手架。最终，FGM可以用可吸收性材料来替代用于外科骨损伤手术治疗的永久性硬件，该材料允许自然骨骼再生。 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.当前的干细胞驱动再生方法受到限制，因为募集干细胞并在分化为功能组织时支持其保留率的支架。 FGM提供了在任何其他单一材料中都找不到的独特属性面板，因此有可能克服这些局限性。具体而言，FGM提供自动降解性，机械性能和远距离顺序，再加上可控的表面化学。氧化石墨烯（GO）提供了众多有机功能，可用于调整表面化学，以最大程度地提高FGM中的细胞相互作用。但是，由于化学界面的控制不足，这些特性的实现受到限制，并且由于无法产生强大的3D支架而受到限制。在这里，将开发新的方法来通过使用Claisen重排和Mitsunobu反应来创建仿生FGM：经典的有机反应，以共价安装仿生部分，直接在生物材料表面安装。在此资助期结束时，该项目将：1）证明Claisen石墨烯CG创建具有启发性表面以促进上层干细胞粘附的能力。 2）证明了使用Mitsunobu石墨烯，MG的蛋白质，定向干细胞分化和共价控制释放的较高稳定性。 3）创新的3DP方法生产适合体内植入的FGM支架。总体而言，这项关于骨骼的工作将提供有关干细胞指导疗法的宝贵见解，并可以释放出多种组织工程疗法中的干细胞定向再生的潜力。除了社会影响之外，该项目还支持Chemcast，这是一个播客，旨在使学生了解研究主题以及包括“自行车的化学”在内的外展活动。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优点和更广泛影响的审查标准来通过评估来支持的。