Abstract:
“In regenerative medicine, the implantation of combined of cells and hydrogels is a promising strategy to improve cell therapy. However, it is crucial to monitor the in vivo fate of hydrogels and cells using non-invasive imaging tools, for optimizing their properties as well as for enabling translation into the clinic. In this context, we proposed to label the injectable and self-healing hyaluronic acid (HA) hydrogel with contrast agents, Iodine for spectral CT (Computed Tomography), Gadolinium or Arginine for advanced MRI (magnetic resonance imaging). In order to demonstrate their interests in cell therapy, their rheological behaviors, cytocompatibilities and in vivo detections were studied with animal models of pathologies such as ischemic stroke or osteoarthritis.
Firstly, this thesis work presents the synthesis and in vivo monitoring of an iodine-labelled HA hydrogel (acetrizoic acid) for spectral tomography (SKES-CT, Synchrotron K-Edge Substraction Computed Tomography). This HA-I hydrogel demonstrated rheological properties and cytocompatibility with human mesenchymal adipose stem cells (hADSC) used in cell therapy. Combined with gold-labelled human adipose stem cells (11-MUDA gold nanoparticles, AuNPs), a “repair kit” was formulated and studied in animal models with Synchrotron X-ray bicolor imaging (SKES-CT). Using this imaging technique, the HA-I hydrogel and AuNPs-hADSC cells were selectively monitored in vivo and ex-vivo on biological tissues.
In a second part, two HA hydrogels labelled with Gadolinium (T1 MRI) or Arginine (CEST MRI) were developed in parallel for advanced magnetic resonance imaging (MRI). After validating their rheological behaviors, in vitro detections and cytocompatibilities with hADSC, these HA-GdDOTA and HA-Arginine hydrogels were intracerebrally injected into healthy brains (rats). Longitudinal follow-up allowed to validate the stability of the contrasts (Gadolinium or Arginine) in vivo over a period of 30 days, demonstrating the ability to be monitored by advanced magnetic resonance imaging.”
