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

摘要：本项目旨在开发一种支持损伤后骨再生的可吸收支架。干细胞在促进骨再生方面具有很大的前景，但目前的支架缺乏保留和向干细胞提供信号以使其在损伤部位转化为骨形成细胞的能力。为了克服这些限制，功能石墨材料（fgm）前景光明。石墨储量丰富，可以通过化学修饰形成fgm。fgm具有优异的可调节的机械性能、可降解性和可控制的表面化学，可转化为可调节的生物活性。然而，由于没有合适的处理方法，这还不可能实现。在这里，PI将开发具有保留和指导骨形成细胞愈合反应能力的新女性生殖器官。此外，PI将为这些女性生殖器官开发3D打印方法，为患者创建个性化支架。最终，女性生殖器官可以用一种可吸收的材料取代用于外伤性骨损伤手术治疗的永久性硬体，这种材料可以使天然骨再生。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，赋予妇女和代表性不足的人群权力，并让她们参与进来。技术摘要：本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，该材料将作为骨干细胞再生的支架。目前干细胞驱动再生的方法是有限的，因为在干细胞分化成功能组织时，需要一个支架来招募干细胞并支持它们的保留。fgm提供了任何其他单一材料所没有的独特性能面板，因此具有克服这些限制的潜力。具体来说，fgm具有自降解性、机械性能和长程有序性，并且具有可控的表面化学性质。氧化石墨烯（GO）提供了大量的有机功能，可用于调整表面化学，以最大限度地提高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了限制，并且由于无法生产出坚固的3D支架，应用也受到了限制。在这里，将开发新的方法，通过使用Claisen重排和Mitsunobu反应来创建仿生女性生殖器官：经典的有机反应，将仿生部分直接安装在生物材料的表面。在本资助期结束时，该项目将：1)证明clisen石墨烯（CG）能够创造一个具有指导意义的表面，以促进卓越的干细胞粘附。2)利用光信石墨烯（Mitsunobu Graphene， MG）展示优越的蛋白质稳定性、定向干细胞分化和共价控释。3)创新3d打印技术，生产适合体内植入的女性生殖器切割支架。总的来说，这项关于骨骼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。除了社会影响之外，这个项目还支持ChemCast，一个旨在让学生了解最新研究主题的播客，以及包括“骑自行车的化学”在内的外展活动。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.