The compounds object of the invention are a new metal-free class of contrast agents for magnetic resonance, whose action is based on an innovative mechanism that do not use potentially toxic metals. The compounds work at fixed frequencies and they may be used for the design of nano- and micro- devices reporting on local pathological and physiological changes, in vitro and in vivo
The problem that this patent aims to solve regards the nature of Contrast Agents (CAs) for MRI and their use as reporter in Regenerative Medicine. The most currently used CAs in clinical MRI contain gadolinium. Since a correlation is known between their use and the occurrence of a potentially fatal multiorgan disease (Nephrogenic Systemic Fibrosis) in patients with renal failure and of a non specific Gd accumulation in different organs (in particular in brain) of patients who have received multiple doses, main efforts are devoted on the development of alternative metal free contrast agents. The new biomaterial herein developed can be used to produce nanosystems, for tumor diagnosis or tissue scaffolds for regenerative medicine applications, that can be monitored in a non-invasive and repeatable way.
We develop innovative sensors to monitor non-invasively the status of tissue implants by Fast Field-Cycling imaging. These sensors enhance image contrast thanks to the 14N of imidazole groups of histidine, which are conjugated to the PLGA (poly lactic and glycolic acid) polymeric chains forming the scaffold structural matrix. These completely new polymeric sensors are pH-sensitive, biocompatible and biodegradable; they differ completely from current clinical contrast agents (which contain potentially toxic paramagnetic metals) and can report continuously on scaffold degradation and cell proliferation, non-invasively.
Our technology and solutions
The new technology concerns the development of a new class of metal-free contrast agents (CAs) containing histidine for Fast Field Cycling Magnetic Resonance applications. This technique involves the acquisition of images and / or longitudinal relaxation rate at variable magnetic field strengths. The contrast is generated by the interaction of H2O with quadrupolar 14N of the imidazole group of histidine. This CA is pH-sensitive and useful to obtain biocompatible surgical implant that can be monitored in vivo.
Tissue scaffolds are excellent tools for the regeneration of tissues such as bone, cartilage or cornea, providing initial mechanical support until the regenerated tissue stabilises. However, successful regeneration depends strongly on their stability. It is crucial to assess their status in vivo after insertion to take early corrective actions. No solution currently exists that allows non-invasive monitoring of the viability of implanted scaffolds. Our metal free CA has the unique ability to monitor the tissue scaffold in vivo, non-invasively and repeatedly after its implantation in the target tissue, paving the way to monitoring strategies. We expect that regular monitoring will dramatically improve patient outcome by allowing early corrective actions in order to maintain the scaffold’s structural integrity.
The University of Torino will create a university spin-off devoted to the commercialisation of the histidine-containing polymers. These will be integrated into commercial scaffold products. In parallel, the University of Aberdeen is currently moving towards the commercialisation of FFC-MRI scanners. Dedicated units will be tailor-made for scans of joint scaffolds. To reach this aim, the biocompatibility of the “intelligent and innovative” scaffolds first has to be proven robustly, using a range of cell-culture and animal models.