Bone Regeneration Guided by a Magnetized Scaffold in an Ovine Defect Model.

The reconstruction of large segmental defects still represents a critical issue in the orthopedic field. The use of functionalized scaffolds able to create a magnetic environment is a fascinating option to guide the onset of regenerative processes. In the present study, a porous hydroxyapatite scaffold, incorporating superparamagnetic Fe3O4 nanoparticles (MNPs), was implanted in a critical bone defect realized in sheep metatarsus. Superparamagnetic nanoparticles functionalized with hyperbranched poly(epsilon-Lysine) peptides and physically complexed with vascular endothelial growth factor (VEGF) where injected in situ to penetrate the magnetic scaffold. The scaffold was fixed with cylindrical permanent NdFeB magnets implanted proximally, and the magnetic forces generated by the magnets enabled the capture of the injected nanoparticles forming a VEGF gradient in its porosity. After 16 weeks, histomorphometric measurements were performed to quantify bone growth and bone-to-implant contact, while the mechanical properties of regenerated bone via an atomic force microscopy (AFM) analysis were investigated. The results showed increased bone regeneration at the magnetized interface; this regeneration was higher in the VEGF-MNP-treated group, while the nanomechanical behavior of the tissue was similar to the pattern of the magnetic field distribution. This new approach provides insights into the ability of magnetic technologies to stimulate bone formation, improving bone/scaffold interaction.

Versatile magnetic configuration for the control and manipulation of superparamagnetic nanoparticles.

The control and manipulation of superparamagnetic nanoparticles (SP-MNP) is a significant challenge and has become increasingly important in various fields, especially in biomedical research. Yet, most of applications rely on relatively large nanoparticles, 50 nm or higher, mainly due to the fact that the magnetic control of smaller MNPs is often hampered by the thermally induced Brownian motion. Here we present a magnetic device able to manipulate remotely in microfluidic environment SP-MNPs smaller than 10 nm. The device is based on a specifically tailored configuration of movable permanent magnets. The experiments performed in 500 µm capillary have shown the ability to concentrate the SP-MNPs into regions characterized by different shapes and sizes ranging from 100 to 200 µm. The results are explained by straightforward calculations and comparison between magnetic and thermal energies. We provide then a comprehensive description of the magnetic field intensity and its spatial distribution for the confinement and motion of magnetic nanoparticles for a wide range of sizes. We believe this description could be used to establish accurate and quantitative magnetic protocols not only for biomedical applications, but also for environment, food, security, and other areas.

Multifunctional 3D-Printed Magnetic Polycaprolactone/Hydroxyapatite Scaffolds for Bone Tissue Engineering.

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.

Application of magnetic rods for fixation in orthopedic treatments.

Achieving an efficient fixation for complicated fractures and scaffold application treatments is a challenging surgery problem. Although many fixation approaches have been advanced and actively pursued, the optimal solution for long bone defects has not yet been defined. This paper promotes an innovative fixation method based on application of magnetic forces. The efficiency of this approach was investigated on the basis of finite element modeling for scaffold application and analytical calculations for diaphyseal fractures. Three different configurations have been analyzed including combinations of small cylindrical permanent magnets or stainless steel rods, inserted rigidly in the bone intramedullary canals and in the scaffold. It was shown that attractive forces as high as 75 N can be achieved. While these forces do not reach the strength of mechanical forces in traditional fixators, the employment of magnetic rods is expected to be beneficial by reducing considerably the interface micromotions. It can additionally support magneto-mechanical stimulations as well as enabling a magnetically assisted targeted delivery of drugs and other bio-agents.

Multilayered Magnetic Gelatin Membrane Scaffolds.

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.

Biomimetic magnetic silk scaffolds.

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 new approach to scaffold fixation by magnetic forces: Application to large osteochondral defects.

Scaffold fixation represents one of the most serious challenges in osteochondral defect surgery. Indeed, the fixation should firmly hold the scaffold in the implanted position as well as it should guaranty stable bone/scaffold interface for efficient tissue regeneration. Nonetheless successful results have been achieved for small defect repair, the fixation remains really problematic for large defects, i.e. defects with areas exceeding 2cm(2). This paper advances an innovative magnetic fixation approach based on application of magnetic scaffolds. Finite element modeling was exploited to investigate the fixation efficiency. We considered three magnetic configurations: (1) external permanent magnet ring placed around the leg near the joint; (2) four small permanent magnet pins implanted in the bone underlying the scaffold; (3) four similarly implanted stainless steel pins which magnetization was induced by the external magnet. It was found that for most appropriate magnetic materials and optimized magnet-scaffold positioning all the considered configurations provide a sufficient scaffold fixation. In addition to fixation, we analyzed the pressure induced by magnetic forces at the bone/scaffold interface. Such pressure is known to influence significantly the bone regeneration and could be used for magneto-mechanical stimulation.