Injectable biomaterials are being developed for a wide range of biomedical applications; however, characterization of materials (e.g., distribution, chemical composition) after injection is often difficult and relies on invasive and destructive procedures. To address this problem, this study utilizes a new magnetic resonance imaging (MRI) acquisition technique based on chemical exchange saturation transfer (CEST), where the signal relies on the exchange of protons in specific molecules with bulk water protons. Such a signal can be generated from specific functional groups endogenous to or engineered into a desired material. Here, CEST MRI was used to visualize injectable hyaluronic acid (HA) hydrogels either alone or after injection into tissue. The CEST effect was shown to track with changes in material properties-as hydrogel macromer concentration was increased, the CEST contrast increased linearly. Furthermore, CEST MRI was used to detect hydrogels injected into cardiac explants with an increase in signal at the hydrogel site relative to the surrounding myocardial signal. Unlike conventional MRI, CEST can simultaneously visualize and discriminate between different injectable materials based on their unique chemistry. To illustrate this, we tuned the CEST signal to detect differences in two hydrogel systems based on their dominant functional groups. The covalent addition of an arginine-based peptide to HA hydrogels led to a 2-fold increase in signal when the exchangeable amine (-NH2) protons in the peptide were targeted. Thus, CEST MRI could become a valuable tool for studying injectable hydrogel properties and enable further optimization of biomaterial therapies aimed at clinical translation.
Keywords: chemical exchange saturation transfer; hyaluronic acid; hydrogel; magnetic resonance imaging.