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

Abstract

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.

Nanocrystalline Yttria-Stabilized Zirconia Ceramics for Cranial Window Applications

“…Similarly, in this study, under indirect contact conditions, the average cell adhesion densities in the nanoparticle control groups were lower than that in other groups, as shown in Figure b. Fortunately, it is known that most nanoparticles have dosage-dependent cytotoxicity. , Densified YSZ discs are generally regarded as nondegradable materials in human body fluids and are not expected to release nanoparticles. Thus, the concentration we used in the control groups (10 mM) represents the worst and unlikely scenario when cells might be exposed to YSZ nanoparticles.…”

“…Fortunately, it is known that most nanoparticles have dosage-dependent cytotoxicity. 36,37 Densified YSZ discs are generally regarded as nondegradable materials in human body fluids and are not expected to release nanoparticles. Thus, the concentration we used in the control groups (10 mM) represents the worst and unlikely scenario when cells might be exposed to YSZ nanoparticles.…”

“…Following the protocol approved by the Institutional Animal Care and Use Committee (IACUC) at the University of California at Riverside (UCR), rat BMSCs were harvested and cultured similarly as described in our previous work. − Briefly, the distal and proximal ends of the femoral and tibial bones were dissected, and the bone marrow was flushed out of the bone cavity by Dulbecco’s modified Eagle’s medium (DMEM, #SLBC9050, high glucose, D5648, Sigma-Aldrich, St. Louis, MO) supplemented with 10% fetal bovine serum (FBS, HyClone, #SH30910, Thermo Fisher Scientific Inc., Waltham, MA) and 1% penicillin/streptomycin (P/S, HyClone, #SV30010, Thermo Fisher Scientific, Inc., Waltham, MA) using a syringe and collected in the centrifuge tube. Hereafter, the complete DMEM supplemented with 10% FBS and 1% P/S is referred to as the culture media in this study.…”

Cell-Penetrating Peptidic GRP78 Ligand-Conjugated Iron Oxide Magnetic Nanoparticles for Tumor-Targeted Doxorubicin Delivery and Imaging

“…Our results share a number of similarities with those of Zhang and Daya et al's findings, of which hydrogel-based magnetic nanoparticles taken in by bone marrow-derived mesenchymal stem cells did not enter the nucleus and were present in the cytoplasm. 54,55 In this study, doxorubicin in the MDA-MB-468 cell line was reported, which lacks the GRP78 receptor; the expression of this protein on the cell surface could increase, while in the BT-474 cell line with the related receptor, no increase was observed in the GRP78 protein expression. 56 This behavior may be attributed to the fact that the BT-474 cell line has the amount of the GRP78 receptor before DOX was added, and therefore, the presence of the drug had no effect on the protein re-expression.…”

“…In other words, magnetic nanoparticles could be detected in the cytoplasm of the cells but outside of the cell nuclei. Our results share a number of similarities with those of Zhang and Daya et al’s findings, of which hydrogel-based magnetic nanoparticles taken in by bone marrow-derived mesenchymal stem cells did not enter the nucleus and were present in the cytoplasm. , …”