Angiogenic magnetic hydrogels are attractive for tissue engineering applications because their integrated properties can improve angiogenesis while providing magnetic guidance and stimulation for tissue healing. In this study, we synthesized magnetic nanoparticles (MNPs) with curcumin as an angiogenic agent, referred to as CMNPs, via a one-pot coprecipitation method. We dispersed CMNPs in hyaluronic acid (HyA) to create angiogenic magnetic hydrogels. CMNPs showed a slightly reduced average diameter compared to that of MNPs and a curcumin content of 11.91%. CMNPs exhibited a sustained slow release of curcumin when immersed in a revised simulated body fluid (rSBF). Both CMNPs and MNPs showed a dose-dependent cytocompatibility when cultured with bone marrow-derived mesenchymal stem cells (BMSCs) using the direct exposure culture method in vitro. The average BMSC density increased when the concentrations of CMNPs or MNPs increased from 100 to 500 μg/mL, but the cell density decreased when the nanoparticle concentration reached 1000 μg/mL. CMNPs showed a weaker magnetic response than MNPs both in air and in water immediately after synthesis but retained the magnetism better than MNPs when embedded in the HyA hydrogel because of less oxidation. CMNPs were able to respond to magnetic guidance even when the porcine skin or muscle tissues were placed in between the nanoparticles and external magnet. The magnetic hydrogels of HyA_CMNP and HyA_MNP promoted the adhesion of BMSCs in a direct exposure culture. The HyA_CMNP group also showed the highest secretion of the vascular endothelial growth factor with the release of curcumin in vitro. Overall, our magnetic hydrogels integrated the desirable properties of cytocompatibility and angiogenesis with magnetic guidance, thus proving to be promising for improving tissue regeneration.
Keywords: angiogenesis; bone marrow-derived mesenchymal stem cells (BMSCs); curcumin; cytocompatibility; hyaluronic acid (HyA) hydrogels; iron oxide magnetic nanoparticles (MNPs).