Apical release from endodontic hydrogels: An in vivo study

Hydrogels are promising materials in tissue engineering, given their biocompatibility and versatility. However, the impact of galenic parameters on hydrogel behavior in specific anatomical contexts, such as partial or complete pulp regeneration, remains understudied. Galenic properties, which are crucial for clinical efficacy, are impacted by numerous parameters. The aim herein was to evaluate the influence of three key parameters in vivo (two pharmaceutical formulation parameters, the hydrogel concentration and the nanoparticle hydrophobicity, and one anatomical parameter, the apical diameter) on the galenic behavior of hydrogels used in endodontic regeneration, using an innovative standardized model, and live imaging. An in vivo model was developed to assess the release from fibrin hydrogels in endodontic-simulated clinical conditions. The model was implanted in the back of hairless mice. Three key parameters were evaluated: 1) apical diameter; 2) hydrogel concentration; and 3) nanoparticle physicochemical properties (hydrophobicity). Fluorescence molecular tomography was used for live monitoring, and statistical analysis was performed to determine significance. Reduced apical diameters (from 2000 to 1000 µm) led to an 87.5-94.2% reduction in the apical release over the first 48 h. Fibrin-based hydrogels exhibited a smaller burst effect upon increased hydrogel concentration (reduced by 65.9% during the first hour). Vectorization on a hydrophobic nanoparticle diminished apical release rate compared to vectorization on a hydrophilic nanoparticle over 6 days. The present study found that at least three parameters significantly influence apical release in vivo: the apical diameter, hydrogel concentration, and hydrophobicity, individually and, possibly, through their interactions. This provides essential insights into optimizing hydrogel formulations for clinical purposes.