"Magnetically responsive nanoparticle-vesicle hydrogels as ""smart"" biomaterials for the spatiotemporal control of cellular responses"
Date du début: 1 mai 2013,
Date de fin: 30 avr. 2015
This project will develop a new “smart” self-assembled biomaterial containing supramolecular magnetic nanoparticle-vesicle assemblies (MNPVs) as the active elements, which are able to convert non-invasive magnetic signals into biochemical responses in cells. This new biomaterial will have enhanced biocompatibility and allow spatiotemporal control over the release of bioactive compounds from MNPVs in the hydrogel. To achieve temporal control, a dual-release mechanism will be built into the biomaterial so that a short duration magnetic pulse will release a bioactive compound and elicit a cellular response, followed by a longer duration “self-destruct” magnetic pulse that will release enzyme/reagents able to dissociate the MNPVs and the surrounding hydrogel. Both non-covalent and enzymatically cleavable linkages between magnetic nanoparticles and vesicles and in the hydrogel matrices will be assayed. This second “self-destruct” signal will facilitate non-invasive clearance of the synthetic hydrogel either in vivo or in vitro without mechanical damage to the cells. To achieve spatial control, the hydrogel will be magnetically patterned at the macro and micro scale during the preparation of the vesicle gels. Furthermore, to increase the hospitability of the prepared biomaterials across cell types and target the MNPVs to certain cell lines, glycolipids and lipopeptides will be synthesized chemically/chemoenzymatically and doped into MNPVs. Throughout the project, each magnetically responsive biomaterial will be tested as a cell culture platform, with the effect of the released compounds on the cells assessed using standard assays, like cell counting, MTT for metabolic activity, DNA assays for cell proliferation, flow cytometry and real time PCR. Obtaining spatiotemporal control over cells cultured in these “smart” self-assembled biomaterials will open a path towards exciting potential applications in tissue engineering and regenerative medicine.
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