# Tuning the Cell and Biological Tissue Environment through Magneto-Active Materials
## 6 Magneto-Active Polymers in Biomedical Applications
### MAPs for Bone and Tendon Tissue Engineering  
MAP systems present unique characteristics that make them ideal candidates for application in tissue regeneration. For instance, a current challenging problem is the repair of large bone injuries due to trauma, tumour removal or diseases, such as osteoporosis. During the bone regeneration process, scaffolds play an important role, providing adequate biological environment and promoting cell adhesion, proliferation and differentiation [189; 200]. These scaffolds must comprise at least two properties: biocompatibility and degradability [201]. Conceptualising magneto-active scaffolds allows for remote mechanical stimulation transmitting forces to the cells or altering the mechanical properties of the surrounding environment, thus promoting better bone regeneration [189; 201]. To this end, magnetic-induced changes in their properties can simulate load bearing in healing bone or tendons, where actual loads cannot be applied but are still essential to the correct  
Figure 5: Bioengineering applications of magneto-active polymers in: (**A**) bone tissue engineering: mechanical stimulation based on the deformation of a magnetic composite leads to enhanced osteogenic differentiation (adapted with permission from [193]); (**B**) drug delivery: alginate ferrogel deformation by application of a magnetic field leads to controlled drug release (adapted with permission from [191]); (**C**) hyperthermia treatment: application of a magnetic ferrogel (PNIPAm-Fe\({}_{3}\)O\({}_{4}\)) for tumour encasing and hyperthermia cancer therapy (adapted with permission from [144]); (**D**) soft robotics (adapted with permission from [190]); (**E**) neuronal regeneration: remote magnetic orientation of collagen fibres in a hydrogel for directed neuronal regeneration (adapted with permission from [198]). differentiation and repair of these structures. Previous studies have reported that they can overexpress osteogenic markers and activate vascular differentiation [202, 203]. One of the first attempts of using magnetic hydrogels for tissue engineering was the creation of aligned collagen-fibrils hydrogels by the addition of streptavidin coated magnetic beads. By the application of an external magnetic field (EMF), aligned collagen fibrils were obtained in both plain and cell-bearing gels, at least a few millimetres thick [204]. Based on this idea, [PERSON] et al. [205] developed a novel approach, which included the incorporation of MNPs to hydroxyapatite (HA) scaffolds directly during the HA nucleation. This means that the MNPs become an intrinsic component of the scaffold. The fabrication of these scaffolds, with gradients in magnetisation and mineralisation, created a novel model for osteochondral differentiation. [PERSON] et al. [206] developed a magnetic scaffold by dip-coating a conventional HA/Coll scaffold for bone tissue engineering in a ferromagnetic fluid. By this technique, the porosity of the scaffolds allows the ferrofluids to be drawn inside the structure by capillarity. These scaffolds were shown to be able to maintain cell culture with no observable effect on the morphology or survivability of the cells. [PERSON] et al. [207] used a photocrosslinkable magnetic hydrogel made of methacrylate-chondroitin sulphate (MA-CS) enriched with platelet lysate, with encapsulated MA-CS coated iron-based magnetic particles. EMF application modulated the swelling degradation and release of PL-derived growth factors and impacted both cell morphogenesis and expression and synthesis of tendon- and bone-like matrices. [PERSON] et al. [208] reported the synthesis of collagen-based nanocomposite hydrogels with tuneable properties. The technique used for the magnetisation of the hydrogel was the dip-coating of the scaffold on a ferrofluid of hydrophilic magnetite nanoparticles. A study was carried out on the morphology, composition, magnetic properties and mechanical response of the scaffold. [PERSON] et al.