Poly-histidine scaffolds: a new smart material for regenerative medicine applications

Abstract Polymers are a versatile material, with various composition. They can find applications in many fields of Biotechnology. Thanks to the different properties of these biomaterials it is possible to obtain scaffolds, filaments, nanoparticles which can be conjugated with active biomolecules. This thesis is focused on the development of an innovative smart biomaterial conjugated with innovative sensors able to non-invasively monitor the status of tissue implants by Fast Field Cycling magnetic resonance imaging. These sensors are based on oligo-Histidine moieties that are conjugated to poly lactic and glycolic (PLGA) polymers representing the structural matrix of cells hosting scaffolds. The presence of imidazole 14N atoms of histidine causes a relaxation enhancement (also called Quadrupolar Peak, QP) at 1.39 MHz where the proton nuclear magnetic resonance (NMR) frequency and the 14N nuclear quadrupole resonance frequency coincide. This QP falls at a frequency well distinct from the QPs generated by endogenous semisolid proteins (i.e. 0.7, 2.1 and 2.8 MHz). The relaxation enhancement is pH dependent in the range 6.5-7.5, thus it can act as reporter of the scaffold integrity as it progressively degrades upon lowering the micro-environmental pH. The ability of this new class of contrast agents to generate contrast in an image acquired at 1.39 MHz on a Fast Field Cycling-Magnetic Resonance Imaging (FFC-MRI) scanner was assessed. A good biocompatibility of the Histidine containing PLGA scaffolds was observed after its surgical implantation on the back of healthy mice. Upon time the scaffold was colonized by endogenous fibroblasts and this phenomenon was accompanied by a progressive decrease of the intensity of the relaxation peak. The ongoing processes were validated histologically. The obtained results demonstrated the responsiveness of the new material to report on the degradation of the scaffold and showed the role of the FFC-NMR/MRI scanner for the acquisition of images at low magnetic field strength.