Heparinized Acellular Hydrogels for Magnetically Induced Wound Healing Applications

Abstract

The control of angiogenesis has the potential to be used for regulation of several pathological and physiological processes, which can be instrumental on the development of anticancer and wound healing therapeutical approaches. In this study, mesenchymal stem/stromal cells (MSCs) were seeded on magnetic-responsive gelatin, with or without heparin functionalization, and exposed to a static 0.08 T magnetic field (MF), for controlling their anti-inflammatory and angiogenic activity, with the aim of accelerating tissue healing. For the first time, it was examined how the amount of heparin and magnetic nanoparticles (MNPs) distributed on gelatin scaffolds affected the mechanical properties of the hydrogels and the morphology, proliferation, and secretome profiling of MSCs. The findings demonstrated that the addition of MNPs and heparin affects the hydrogel swelling capacity and renders distinct MSC proliferation rates. Additionally, MF acts as a topographical cue to guide MSCs alignment and increases the level of expression of specific genes and proteins that promote angiogenesis. The results also suggested that the presence of higher amounts of heparin (10 μg/cm 3 ) interferes with the secretion and limits the capacity of angiogenic factors to diffuse through the hydrogel and into the culture medium. Ultimately, this study shows that acellular heparinized hydrogels efficiently retain the angiogenic growth factors released by magnetically stimulated MSCs thus rendering superior wound contraction (55.8% ± 0.4%) and cell migration rate (49.4% ± 0.4%), in comparison to nonheparinized hydrogels (35.2% ± 0.7% and 37.8% ± 0.7%, respectively). Therefore, these heparinized magnetic hydrogels can be used to facilitate angiogenesis in various forms of tissue damage including bone defects, skin wounds, and cardiovascular diseases, leading to enhanced tissue regeneration.

Extracellular Matrix Mimicking Wound Microenvironment Responsive Amyloid–Heparin@TAAgNP Co-Assembled Hydrogel: An Effective Conductive Antibacterial Wound Healing Material

“…Furthermore, on day 18, both CD31 and α-SMA expressions in the LZ-HS(2:1) ( p < 0.001, p < 0.001) and LZ-HS(2:1)@TA AgNP20 -treated groups ( p < 0.001, p < 0.001) were found to be persistently higher than that of the control and Mupirocin-treated ones, which is quite obvious, since several angiogenic growth factors, such as VEGF and FGF, can improve the chances of angiogenesis by localization at the LZ-HS hydrogel vicinity by virtue of their heparin sulfate-binding phenomenon (Figures C and D). In conclusion, the results of the experimental immunofluorescence study provided additional evidence that the hybrid hydrogel composed of LZ-HS(2:1)@TA AgNP20 is effective in reducing inflammation and promoting the regeneration and maturation of blood vessels in the vicinity of the wound. , This, in turn, contributes to the overall healing performance in diabetic full-thickness wound models infected with multispecies drug-resistant bacteria.…”

The Recent Applications of Magnetic Nanoparticles in Biomedical Fields

“…The surface modification of MNPs utilized various functional groups, which can immobilize different biological ligands in the analyte [ 59 ]. Commonly used MNPs include histidine-tagged MNPs [ 91 ], diethylaminoethylcellulose MNPs [ 92 ], heparin MNPs [ 93 ], flag-labeled MNPs, antibody MNPs (Protein A/Protein G/Protein L) [ 94 , 95 ], Strep-tag II MNPs [ 96 ], adapter MNPs [ 97 ], and solid-phase peptide MNPs [ 98 , 99 ], primarily for the purpose of separating and purifying the analyte.…”