Date of Award
Doctor of Philosophy (PhD)
Nagatomi , Jiro
Simionescu , Dan
Visconti , Richard P.
Magnetic nanoparticles (MNPs) have been investigated in tissue engineering applications to provide in situ imaging, drug delivery, and tissue patterning, but direct and prolonged interaction between cells and MNPs can have adverse effects on cell function. Therefore, methods which reduce or limit the interaction of MNPs with cells, or utilize more biocompatible MNP-based strategies will improve upon the commonly used iron oxide MNPs. We investigated a variety of methods to improve upon the use of MNPS in tissue engineering.
Cell aggregates, or spheroids, have been used as tissue engineered building blocks that can closely mimic the native three-dimensional in vivo environment. Current strategies incorporating MNPs into tissue engineering often involve cellular uptake, however, which can induce adverse effects on cell activity, viability, and phenotype, and should therefore be avoided. Here, we report a Janus structure of magnetic cellular spheroids with spatial control of MNPs to form two distinct domains: cells and extracellular MNPs. This separation of cells and MNPs within magnetic cellular spheroids had no adverse affects on long-term viability or cellular phenotype, allowing for the magnetic manipulation and fusion into controlled patterns and complex tissues.
Iron oxide NPs are the most common MNP in biomedical applications, but these MNPs often require complex surface modifications to improve their biocompatibility. We report the preparation of magnetoferritin NPs, a biological MNP, capable of serving as a biological alternative to iron oxide MNPs. Magnetoferritin NPs were incorporated into three-dimensional cellular spheroids with no adverse effects on cell viability and were capable of magnetic force assembly into fused tissues.
Additionally, the ideal nanomaterial will remain stable for a sufficient amount of time to accomplish its desired task, and then rapidly degrade once that task is completed. We report the use of surface modifications to accelerate iron oxide MNP degradation mediated by polymer encapsulation in polymers with different degradation rates: poly(lactide) (PLA) or copolymer poly(lactide-co-glycolide) (PLGA). Results demonstrated that the degradation of MNPs can be controlled by varying the content and composition of the polymeric nanoparticles used for MNP encapsulation (PolyMNPs). These PolyMNPs maintained a high viability compared to non-coated MNPs, and are also useful in magnetic force assembly into fused tissues. The presented results highlight multiple strategies which can improve upon the biocompatibility of MNPs in tissue engineering applications.
Mattix, Brandon, "Spatial Control of Magnetic Nanoparticles Integrated with Cellular Spheroids as Tissue Engineered Building Blocks" (2013). All Dissertations. 1185.