A review on the effect of nanocomposite scaffolds reinforced with magnetic nanoparticles in osteogenesis and healing of bone injuries.

Many problems related to disorders and defects of bone tissue caused by aging, diseases, and injuries have been solved by the multidisciplinary research field of regenerative medicine and tissue engineering. Numerous sciences, especially nanotechnology, along with tissue engineering, have greatly contributed to the repair and regeneration of tissues. Various studies have shown that the presence of magnetic nanoparticles (MNPs) in the structure of composite scaffolds increases their healing effect on bone defects. In addition, the induction of osteogenic differentiation of mesenchymal stem cells (MSCs) in the presence of these nanoparticles has been investigated and confirmed by various studies. Therefore, in the present article, the types of MNPs, their special properties, and their application in the healing of damaged bone tissue have been reviewed. Also, the molecular effects of MNPs on cell behavior, especially in osteogenesis, have been discussed. Finally, the present article includes the potential applications of MNP-containing nanocomposite scaffolds in bone lesions and injuries. In summary, this review article highlights nanocomposite scaffolds containing MNPs as a solution for treating bone defects in tissue engineering and regenerative medicine.

PCL/Col I-based magnetic nanocomposite scaffold provides an osteoinductive environment for ADSCs in osteogenic cues-free media conditions.

BACKGROUND: The bone tissue engineering (BTE) approach has been introduced as an alternative to conventional treatments for large non-healing bone defects. Magnetism promotes stem cells' adherence to biocompatible scaffolds toward osteoblast differentiation. Furthermore, osteogenic differentiation media are expensive and any changes in its composition affect stem cells differentiation. Moreover, media growth factors possess a short half-life resulting in the rapid loss of their functions in vivo. With the above in mind, we fabricated a multilayered nanocomposite scaffold containing the wild type of Type I collagen (Col I) with endogenous magnetic property to promote osteogenesis in rat ADSCs with the minimum requirement of osteogenic differentiation medium. METHODS: Fe3O4 NPs were synthesized by co-precipitation method and characterized using SEM, VSM, and FTIR. Then, a PCL/Col I nanocomposite scaffold entrapping Fe3O4 NPs was fabricated by electrospinning and characterized using SEM, TEM, AFM, VSM, Contact Angle, tensile stretching, and FTIR. ADSCs were isolated from rat adipose tissue and identified by flow cytometry. ADSCs were loaded onto PCL/Col I and PCL/Col I/Fe3O4-scaffolds for 1-3 weeks with/without osteogenic media conditions. The cell viability, cell adhesion, and osteogenic differentiation were evaluated using MTT assay, SEM, DAPI staining, ALP/ARS staining, RT-PCR, and western blotting, respectively. RESULTS: SEM, VSM, and FTIR results indicated that Fe3O4 was synthesized in nano-sized (15-30 nm) particles with spherical-shaped morphology and superparamagnetic properties with approved chemical structure as FTIR revealed. According to SEM images, the fabricated magnetic scaffolds consisted of nanofiber (500-700 nm). TEM images have shown the Fe3O4 NPs entrapped in the scaffold's fiber without bead formation. FTIR spectra analysis confirmed the maintenance of the natural structure of Col I, PCL, and Fe3O4 upon electrospinning. AFM data have shown that MNPs incorporation introduced stripe-like topography to nanofibers, while the depth of the grooves has decreased from 800 to 500 nm. Flow cytometry confirmed the phenotype of ADSCs according to their surface markers (i.e., CD29 and CD105). Additionally, Fe3O4 NP improved nanocomposite scaffold strength, wettability, porosity, biocompatibility and also facilitates the ALP activity, calcium-mineralization. Finally, magnetic nanocomposite scaffolds upregulated osteogenic-related genes or proteins' expression (e.g., Col I, Runx2, OCN, ON, BMP2) in seeded ADSCs with/without osteo-differentiation media conditions. CONCLUSIONS: Together, these results indicate that Fe3O4 NPs within the natural structure of Col I increase osteogenic differentiation in osteogenic cues-free media conditions. This effect could be translated in vivo toward bone defects healing. These findings support the use of natural ECM materials alongside magnetic particles as composite scaffolds to achieve their full therapeutic potential in BTE treatments.