This project aims at developing innovative biocompatible sensors able to monitor the status of tissue implants in vivo, at human scale. These sensors are aimed at reporting on the degradation of the scaffold and on the overall transplanted cells conditions. They represent a completely new class of MRI contrast agents that display remarkable relaxation effects on tissue water protons. Their detection requires the acquisition of images at variable magnetic field strength as provided by Fast Field Cycling MRI (FFCMRI) scanners.
The peculiar property of the proposed sensors relies on the generation of 14NQuadrupolar Peaks (QPs) that cause a relaxation enhancement of water protons at the proton NMR frequency corresponding to the 14N quadrupolar resonance frequency. The QPs from the sensor has to fall at frequencies well distinguishable from those associated with the amidic peptide bonds from endogenous proteins.
This project relies on an innovative technology, FFC-MRI, which opens new avenues for non-invasive imaging technologies with human applications. The uniqueness of this technology relies on its ability to image how the magnetic relaxation time of materials varies with the magnetic field strength. In particular, FFC allows detecting the quadrupolar cross-relaxation, appearing as peaks (QPs) in the 1/T1 dispersion profile completely invisible to conventional (fixed-field) MRI.
Research conducted by our groups has demonstrated that exogenous poly-Histidine (poly-His) of different sizes shows QPs at a frequency well distinguishable from the endogenous ones, and therefore it may be used as a new class of frequency-encoded specific sensor. The poly-His QPs are detectable only when the polymer is in a gelified or solid-like form, ie at pH>6.6, and above this value their intensity is pH dependent. Thanks to this pH-dependent behaviour, a poly-His sensor can be used to report on tissue pH changes (that can be associated to cellular apoptosis/necrosis). Scaffold will be prepared using polylactic and glycolic acid, i.e. a biodegradable material largely used in clinical applications.
The sensitivity detection limit of the new class of sensors will be determined on the prototype human whole-body sized FFC-MRI scanners available at the Aberdeen University.
The direct outcome of this project will be to lift a technological lock in the development of tissue regenerative medicine. We expect that this technique will dramatically boost the in vivo study of scaffolds, allowing proof-of-concepts to be performed according to clinical standard so that new products will be able to reach the market. In fact, to date there is an almost complete lack of methods for the rapid, non-invasive and repeated monitoring of tissue implants and new methods are needed to monitor cell status and polymer degradation under physiological conditions (temperature, saline, pH, enzymes etc.) thus allowing the physician to control, in real time, the transplanted scaffold status.