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Tendon injuries frequently require surgical treatment, and, despite recent advancements in orthopedic surgery, they yield less than optimal results and present the risk of microbial colonization, since the devices used could trigger biomaterial-related infections and biofilm formation. Furthermore, healed tendons tend to form scar tissue with different mechanical properties than healthy ones and are prone to re-injury due to their lack of native tissue complexity. Since tendons are force transmitters and mechanoresponsive tissues, cells within the tendon tissues perceive a complex microenvironment where both environmental cues and cellular mechanotransduction are pivotal in different cell responses, such as apoptosis, proliferation, migration, and differentiation. Recently, biomechano-responsive materials are emerging in tendon tissue engineering. The synergism of stimuli-responsive biomaterials and mechanical stimuli seems fundamental as teno-inductive cues to boost tendon healing. From this perspective, magneto-responsive medical devices (as tendon substitutes) and magnetotherapy should serve as mediators of mechanotransduction to enhance tendon regeneration. The aim of the project is the design and the development of biomechanic-responsive 3D scaffolds able to improve surgical repair or reconstruction of tendons/ligaments. Thermoplastic polymers (polyurethane and polyacrylcyanoacrylate) will be associated with chondroitin sulfate to obtain slow reabsorption (degradation) to guarantee the scaffolds to support the mechanical load until the regeneration of the new tissue is completed. Lyophilized (sponge-like) or electrospun scaffolds will be doped with magnetic iron oxide nanomaterials to obtain a hierarchical structure, responsive to magnetotherapy. The activation of the iron oxide nanomaterials should act as a mediator of mechanotransduction to remotely deliver mechanical stimulation directly to the cells. This should boost tendon healing by achieving teno-inductive cues. Magnetite nanoparticles, the benchmark, and Fe-Mg-hydrotalcites will be compared to evaluate the in vitro efficacy and safety profiles. The 3D scaffolds will be manufactured using both freeze-drying and electrospinning, well-known techniques to obtain hierarchically structured scaffolds for tissue engineering. The two approaches will enable the production of different structures. The sponge-like matrix will be an interconnected structure with pores while the nanofibrous scaffolds will consist of entangled fibers given a certain porosity. Considering these, the mechano stimulation could be differently transmitted to the surrounding and to the infiltrated cells depending on the structure stiffness. Moreover, the reproducibility and the robustness of the manufacturing procedure and the identification of the quality attributes to assure reproducibility of the scaffold will be considered.