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

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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.