Magnetic nanoparticles (MNPs) have been increasingly used in tissue engineering and regenerative medicine. These particles have been mainly employed as elements directly incorporated into cells or interacting with cell membranes; however, MNPs are now being combined with biomaterials to create other functionalities of the structural framework used to support cells, namely for controlling cellular responses and for enhancing drug delivery and release. This mini-review summarizes and highlights the latest developments and applications of polymeric/ceramic biomimetic scaffolds and hydrogels that contain MNPs for such purposes, also addressing future perspectives for the use of these magnetic composite biomaterials in biomedicine.

TGF-β3 is enzymatically immobilized by transglutaminase-2 action to poly(l-lactic acid) microparticles coated with collagen II. Microparticles are then encapsulated with stem cells inside liquified spherical compartments enfolded with a permselective shell through layer-by-layer adsorption. Magnetic nanoparticles are electrostatically bound to the multilayered shell, conferring magnetic-response ability. The goal of this study is to engineer a closed environment inside which encapsulated stem cells would undergo a self-regulated chondrogenesis. To test this hypothesis, capsules are cultured in chondrogenic differentiation medium without TGF-β3. Their biological outcome is compared with capsules encapsulating microparticles without TGF-β3 immobilization and cultured in normal chondrogenic differentiation medium containing soluble TGF-β3. Glycosaminoglycans quantification demosntrates that similar chondrogenesis levels are achieved. Moreover, collagen fibrils resembling the native extracellular matrix of cartilage can be observed. Importantly, the genetic evaluation of characteristic cartilage markers confirms the successful chondrogenesis, while hypertrophic markers are downregulated. In summary, the engineered capsules are able to provide a suitable and stable chondrogenesis environment for stem cells without the need of TGF-β3 supplementation. This kind of self-regulated capsules with softness, robustness, and magnetic responsive characteristics is expected to provide injectability and in situ fixation, which is of great advantage for minimal invasive strategies to regenerate cartilage.

Self-standing nanocomposite films based on biopolymers and functional nanostructures have been widely used due to their potential applications as active elements in biomedical devices. The coupling between chitosan (CHI) and alginate (ALG) multilayered films and magnetic nanoparticles (MNPs) allowed to fabricate magnetic responsive freestanding membranes with a high structural control along the thickness, using the layer-by-layer (LbL) methodology. The mechanical characterization evidenced a trend for an increase of both Young modulus, and ultimate tensile strength with the inclusion of MNPs, or by crosslinking with genipin. Additionally, the multilayered membranes exhibited shape memory properties triggered by hydration. The in vitro biological performance studies showed that cells were more viable and adherent with higher proliferation rates when MNPs were included in the membranes. Our results suggested the potential of the developed magneto-active freestanding membranes for biomedical applications, such as in tissue engineering and biomedical applications.

Magnetically targeted cells with internalized magnetic nanoparticles (MNPs) could allow the success of cell transplantation and cell-based therapies, overcoming low cell retention that occurs when delivering cells by intravenous or local injection. Upon magnetization, these cells could then accumulate and stimulate the regeneration of the tissue in situ. Magnetic targeting of cells requires a detailed knowledge between interactions of engineered nanomaterials and cells, in particular the influence of shape and surface functionalization of MNPs. For the first time, cellular internalization of amino surface-modified iron oxide nanoparticles of two different shapes (nanospheres or nanorods) is studied. MNPs show high cellular uptake and labeled cells could exhibit a strong reaction with external magnetic fields. Compared to nanorods, nanospheres show better internalization efficiency, and labeled cells exhibit strong transportation reaction with external magnetic fields. Contiguous viable cell-sheets are developed by magnetic-force-based tissue engineering. The results confirm that the developed magnetic-responsive nano-biomaterials have potential applicability in tissue engineering or cellular therapies.