A three dimensional magnetic patterning of two cell types was realised in vitro inside an additive manufactured magnetic scaffold, as a conceptual precursor for the vascularised tissue. The realisation of separate arrangements of vascular and osteoprogenitor cells, labelled with biocompatible magnetic nanoparticles, was established on the opposite sides of the scaffold fibres under the effect of nonhomogeneous magnetic gradients and loading magnetic configuration. The magnetisation of the scaffold amplified the guiding effects by an additional trapping of cells due to short range magnetic forces. The mathematical modelling confirmed the strong enhancement of the magnetic gradients and their particular geometrical distribution near the fibres, defining the preferential cell positioning on the micro-scale. The manipulation of cells inside suitably designed magnetic scaffolds represents a unique solution for the assembling of cellular constructs organised in biologically adequate arrangements.Nanotechnology and nanomaterials provide numerous innovative solutions for tissue engineering, aiming at radical reinforcement and renovation of clinical practice. The rapidly growing field of tissue engineering points at the regeneration of damaged tissues, rather than their substitution, and promotes that by implanting templates for tissue regeneration, typically represented by ceramic or polymeric scaffolds 1 . The implantation of bare cell-free scaffolds has serious limitations, especially considering the regular development of the vascular network in the regenerated tissue 2,3 . The most promising solution to this problem is the in vitro pre-loading of scaffolds with cells and/or growth factors before the implantation. The realisation of a correct distribution of cells inside the three-dimensional scaffolds is a key element for the maximally complete regeneration 1,4 . On the other hand, the manipulation and seeding of cells throughout the whole volume of the scaffold is an extremely challenging task and can be partially achieved via technologically sophisticated platforms 5 , barely compatible with routine clinical practice. Moreover, most tissues and organs are composed of various types of cells, preferentially arranged in complex 3D architectures, where they interact with each other and with the organism as a whole 6,7 , complicating further the requisites for a correct pre-loading. A partial solution to this challenging demand consists in the employment of the predominant cell type which defines the main tissue function 8 . This approach is generally suitable for relatively homogeneous tissues, such as cartilage, where tissue development should not be actively supported by other cell types 9 . For other tissues the achievement of efficient vascularisation, cell migration and organisation of the extracellular matrix 10 should be necessarily supported by assembles of different cell types inside the scaffold before implantation 11 .In this paper we propose a new, versatile and easy-to-implement method promoting the three-...
Magnetic silk fibroin protein (SFP) scaffolds integrating magnetic materials and featuring magnetic gradients were prepared for potential utility in magnetic-field assisted tissue engineering. Magnetic nanoparticles (MNPs) were introduced into SFP scaffolds via dip-coating methods, resulting in magnetic SFP scaffolds with different strengths of magnetization. Magnetic SFP scaffolds showed excellent hyperthermia properties achieving temperature increases up to 8 °C in about 100 s. The scaffolds were not toxic to osteogenic cells and improved cell adhesion and proliferation. These findings suggest that tailored magnetized silk-based biomaterials can be engineered with interesting features for biomaterials and tissue-engineering applications.
A versatile approach for the design and fabrication of multilayer magnetic scaffolds with tunable magnetic gradients is described. Multilayer magnetic gelatin membrane scaffolds with intrinsic magnetic gradients were designed to encapsulate magnetized bioagents under an externally applied magnetic field for use in magnetic-field-assisted tissue engineering. The temperature of the individual membranes increased up to 43.7 °C under an applied oscillating magnetic field for 70 s by magnetic hyperthermia, enabling the possibility of inducing a thermal gradient inside the final 3D multilayer magnetic scaffolds. On the basis of finite element method simulations, magnetic gelatin membranes with different concentrations of magnetic nanoparticles were assembled into 3D multilayered scaffolds. A magnetic-gradient-controlled distribution of magnetically labeled stem cells was demonstrated in vitro. This magnetic biomaterial–magnetic cell strategy can be expanded to a number of different magnetic biomaterials for various tissue engineering applications.
Multifunctional and resistant 3D structures represent a great promise and a great challenge in bone tissue engineering. This study addresses this problem by employing polycaprolactone (PCL)-based scaffolds added with hydroxyapatite (HAp) and superparamagnetic iron oxide nanoparticles (SPION), able to drive on demand the necessary cells and other bioagents for a high healing efficiency. PCL-HAp-SPION scaffolds with different concentrations of the superparamagnetic component were developed through the 3D-printing technology and the specific topographical features were detected by Atomic Force and Magnetic Force Microscopy (AFM-MFM). AFM-MFM measurements confirmed a homogenous distribution of HAp and SPION throughout the surface. The magnetically assisted seeding of cells in the scaffold resulted most efficient for the 1% SPION concentration, providing good cell entrapment and adhesion rates. Mesenchymal Stromal Cells (MSCs) seeded onto PCL-HAp-1% SPION showed a good cell proliferation and intrinsic osteogenic potential, indicating no toxic effects of the employed scaffold materials. The performed characterizations and the collected set of data point on the inherent osteogenic potential of the newly developed PCL-HAp-1% SPION scaffolds, endorsing them towards next steps of in vitro and in vivo studies and validations.
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