Angiogenic Hyaluronic Acid Hydrogels with Curcumin-Coated Magnetic Nanoparticles for Tissue Repair

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.