Calcium Phosphate/Hyaluronic Acid Composite Hydrogels for Local Antiosteoporotic Drug Delivery

Despite the bone ability of self-regeneration, large bone defects require surgical intervention. Likewise, when it comes to osteoporotic bone fractures, new approaches should be considered a supportive mechanism for the surgery. In recent years, more and more attention has been attracted to advanced drug delivery systems for local osteoporosis treatment, combining appropriate biomaterials with antiosteoporotic drugs, allowing simultaneously to regenerate the bone and locally treat the osteoporosis. Within the current research, hyaluronic acid/strontium ranelate (HA/SrRan), HA/calcium phosphate nanoparticles (HA/CaP NPs), and HA/CaP NPs/SrRan hydrogels were prepared. The effect of CaP and SrRan presence in the composites on the swelling behavior, gel fraction, molecular structure, microstructure, and SrRan and Sr²⁺ release, as well as in vitro cell viability was evaluated. Obtained results revealed that the route of CaP nanoparticle incorporation into the HA matrix had a significant effect on the hydrogel gel fraction, rheological properties, swelling behavior, and microstructure. Nevertheless, it had a negligible effect on the release kinetics of SrRan and Sr²⁺. The highest cell (3T3) viability (>80%) was observed for HA hydrogels, with and without SrRan. Moreover, the positive effect of SrRan on 3T3 cells was also demonstrated, showing a significant increase (up to 50%) in cell viability if the used concentrations of SrRan were in the range of 0.05-0.2 μg/ml.