Magnetic poly(ε-caprolactone)/iron-doped hydroxyapatite nanocomposite substrates for advanced bone tissue engineering

Abstract

In biomedicine, magnetic nanoparticles provide some attractive possibilities because they possess peculiar physical properties that permit their use in a wide range of applications. The concept of magnetic guidance basically spans from drug delivery and hyperthermia treatment of tumours, to tissue engineering, such as magneto-mechanical stimulation/activation of cell constructs and mechanosensitive ion channels, magnetic cell-seeding procedures, and controlled cell proliferation and differentiation. Accordingly, the aim of this study was to develop fully biodegradable and magnetic nanocomposite substrates for bone tissue engineering by embedding irondoped hydroxyapatite (FeHA) nanoparticles in a poly(1-caprolactone) (PCL) matrix. X-ray diffraction analyses enabled the demonstration that the phase composition and crystallinity of the magnetic FeHA were not affected by the process used to develop the nanocomposite substrates. The mechanical characterization performed through small punch tests has evidenced that inclusion of 10 per cent by weight of FeHA would represent an effective reinforcement. The inclusion of nanoparticles also improves the hydrophilicity of the substrates as evidenced by the lower values of water contact angle in comparison with those of neat PCL. The results from magnetic measurements confirmed the superparamagnetic character of the nanocomposite substrates, indicated by a very low coercive field, a saturation magnetization strictly proportional to the FeHA content and a strong history dependence in temperature sweeps. Regarding the biological performances, confocal laser scanning microscopy and AlamarBlue assay have provided qualitative and quantitative information on human mesenchymal stem cell adhesion and viability/proliferation, respectively, whereas the obtained ALP/DNA values have shown the ability of the nanocomposite substrates to support osteogenic differentiation.

Support for the initial attachment, growth and differentiation of MG-63 cells: a comparison between nano-size hydroxyapatite and micro-size hydroxyapatite in composites

“…These composites also improve the cell spreading and the development of the actin cytoskeleton. 29 Similarly in our study, the cells on composites with nano-HA (particularly N15) showed relatively high concentrations of beta-actin, and also talin, which is a focal adhesion protein associated with the actin cytoskeleton. The beneficial effects of HA particles on the cell adhesion and growth were explained by the increased wettability of the composite material, changes in the material surface topography, improved adsorption of cell adhesion-mediating proteins to the material surface, and also the osteoinductive effect of HA.…”

Harnessing magnetic-mechano actuation in regenerative medicine and tissue engineering

“…Soft and hard materials are susceptible to acquiring magnetic properties through the incorporation of magnetic iron oxide particles, as demonstrated in the development of magnetic hydrogels [85], magnetic bioactive glasses [86] magnetic blends of poly(caprolactone) (PCL)/hydroxyapatite [86], magnetic nanofibrous hydroxyapatite poly-lactide acid (PLA) [87],and magnetic PCL [88]. The methods for incorporation of magnetic particles in biomaterials include doping, blending, in situ precipitation, and the 'graftingonto' method [89].…”

Cell surface engineering with polyelectrolyte-stabilized magnetic nanoparticles: A facile approach for fabrication of artificial multicellular tissue-mimicking clusters

“…To date, most published techniques have employed passive internalization of MNPs via endocytosis, which allows for effective magnetic modification of cells [11][12][13]. However, uptake of MNPs by cells entails several major drawbacks, such as (1) a lengthy internalization process, requiring up to 72 h of co-incubation of MNPs with cells [14,15] and (2) potential toxic effects of early-stage cytoplasminternalized nanoparticles [16].…”