Date of Award
Doctor of Philosophy
Comparative and Experimental Medicine
Madhu S. Dhar
Madhu S. Dhar, David E. Anderson, Gina M. PIghetti, Shawn E. Bourdo
Breakthroughs in tissue engineering are moving at a rapid rate especially in the regenerative bone biofabrication. Technology growth in the field of additive manufacturing (AM) such 3D bioprinting which provides the ability to create biocompatible 3D construct on which a cell source could be seeded is an encouraging substitute to autologous grafts.
This present research aims to biofabricate a construct for bone tissue engineering using AM technology. The biocompatible material was chosen corresponding to bones extracellular matrix (ECM) composition, which demonstrates an inorganic and organic development phase: Poly (lactic-glycolic acid) was chosen as the polymeric matrix of the compound, due to its bioactivity, biocompatibility, and ability to regulate biodegradability to support cell and bone function; graphene-nanoparticle was chosen for mechanical and organic reinforcement to support the mineral phase of the ECM.
A commercial 3D bioprinter called the Aether 1 was used. The printer is a pneumatic based printer, which allows printing from hydrogels to thermo polymers. The bioprinter is located in the Regenerative Medicine Lab in the Large Animal Clinical Sciences.
The first part of our study was to show the relationship of mesenchymal stem cells and graphene-nanoparticles. This was to evaluate the ECM layout on the graphene for biocompatibility and establish markers for supporting osteogenesis. Second part of the research dealt with finding a safe solvent to melt the different molar ratios of PLGA and the blending in of graphene-nanoparticles for low thermodynamic and low-pressure printing. This work dealt with the characterization, constating in the evaluation of different extrusion speeds, pressure values and nozzle diameters to construct a 3D print for testing the biocompatibility and cellular behavior. The final study was to utilize the 3D constructs in a long bone segmental defect model to characterize its in vivo capabilities.
This work proved that the biofabrication of the PLGA+graphene blend could be achieved and repeatable with 3D bioprinting, supports cellular behavior for regeneration and provided results in the long bone defect study.
Newby, Steven D., "Biofabricated Constructs of Carbon-based Nanoparticles with Mesenchymal Stem Cells for Orthopedic Repair. " PhD diss., University of Tennessee, 2021.