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

非技术摘要：该项目旨在开发一种支持损伤后骨再生的可吸收支架。干细胞具有促进骨再生的巨大希望，但目前的支架缺乏保留干细胞并向其提供信号的能力，使其能够在损伤部位转化为骨形成细胞。为了克服这些限制，功能石墨材料(FGM)有望实现。石墨具有丰富的可获得性，可以通过化学修饰形成功能梯度材料。功能梯度材料具有优良的、可调的机械性能、可降解性和可控的表面化学，可转化为可调的生物活性。然而，这还不可能，因为不存在合适的处理方法。在这里，PI将开发新的功能梯度材料，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，为患者创建个性化的支架。最终，功能梯度材料可以用一种允许天然骨再生的可吸收材料来取代创伤骨损伤外科治疗中使用的永久性硬件。除了社会影响，本科生和研究生还将在课堂和实验室接受培训，并开展外联活动，以增强和吸引妇女和代表性不足的人群。技术摘要：该项目旨在开发新的方法来合成和3D打印仿生的功能石墨烯材料(FGM)，这些材料将作为指导骨干细胞再生的支架。目前干细胞再生的方法是有限的，因为有一种支架可以招募干细胞，并在干细胞分化为功能组织时支持它们的保留。功能梯度材料提供了任何其他单一材料所没有的独特的性能面板，因此有可能克服这些限制。具体地说，功能梯度材料具有自降解性、力学性能和长程有序性，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，可用于调节表面化学，以最大限度地提高功能梯度材料中细胞相互作用的生物兼容性。然而，由于对化学界面的控制不足，这些性质的实现受到了限制，并且由于无法制造出坚固的3D支架，应用也受到了限制。在这里，将开发新的方法来创建仿生功能梯度材料，通过克莱森重排和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。在这一资助期结束时，该项目将：1)展示Claisen Graphene(CG)创造具有指导意义的表面以促进卓越干细胞黏附的能力。2)使用Mitsunobu Graphene，MG展示了卓越的蛋白质稳定性、定向干细胞分化和共价控制释放。3)创新3DP方法制备适合体内植入的FGM支架。总体而言，这项关于骨骼的工作将为干细胞定向疗法提供有价值的见解，并可能在过多的组织工程疗法中释放干细胞定向再生的潜力。除了对社会的影响，该项目还支持化学播客，这是一个播客，旨在让学生了解最新的研究主题以及包括“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。

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.