Periodic Reporting for period 4 - 4D-BIOMAP (Biomechanical Stimulation based on 4D Printed Magneto-Active Polymers)
Período documentado: 2025-07-01 hasta 2025-12-31
Living cells and tissues are constantly exposed to mechanical forces that regulate key biological processes such as development, inflammation, cancer progression, regeneration and healing. However, most in vitro biomedical models fail to reproduce the dynamic and heterogeneous mechanical environments found in living tissues, relying instead on static or overly simplified conditions. This limitation reduces the predictive power of preclinical studies and hinders the development of effective therapies.
The 4D-BIOMAP project addressed this challenge by developing technologies to remotely and dynamically control the mechanical properties of cellular and tissue substrates. Existing approaches typically rely on direct mechanical contact or optical activation, which limits the complexity of the mechanical environments that can be generated and their applicability in opaque or three-dimensional systems. To overcome these limitations, the project developed 4D-printed magneto-active materials and experimental platforms that respond mechanically to external magnetic fields, enabling non-invasive, reversible and programmable magneto-mechanical stimulation with precise control over deformation modes, stiffness gradients and temporal evolution. The low magnetic permeability of biological tissues makes this approach particularly suitable for complex in vitro models and future in vivo applications.
Overall, the project delivered an integrated experimental-computational framework combining advanced materials, magnetic actuation and modelling tools, and applied it to study mechanobiological processes in relevant systems such as brain cells, cancer models and three-dimensional hydrogels. In conclusion, 4D-BIOMAP established a new paradigm for mechanobiology by enabling mechanically realistic and programmable stimulation platforms, paving the way for more predictive biomedical models and mechanistically informed therapeutic strategies.
The 4D-BIOMAP project addressed this challenge by developing technologies to remotely and dynamically control the mechanical properties of cellular and tissue substrates. Existing approaches typically rely on direct mechanical contact or optical activation, which limits the complexity of the mechanical environments that can be generated and their applicability in opaque or three-dimensional systems. To overcome these limitations, the project developed 4D-printed magneto-active materials and experimental platforms that respond mechanically to external magnetic fields, enabling non-invasive, reversible and programmable magneto-mechanical stimulation with precise control over deformation modes, stiffness gradients and temporal evolution. The low magnetic permeability of biological tissues makes this approach particularly suitable for complex in vitro models and future in vivo applications.
Overall, the project delivered an integrated experimental-computational framework combining advanced materials, magnetic actuation and modelling tools, and applied it to study mechanobiological processes in relevant systems such as brain cells, cancer models and three-dimensional hydrogels. In conclusion, 4D-BIOMAP established a new paradigm for mechanobiology by enabling mechanically realistic and programmable stimulation platforms, paving the way for more predictive biomedical models and mechanistically informed therapeutic strategies.
The 4D-BIOMAP project was implemented through tightly connected activities that together delivered a disruptive technology for mechanobiological research, integrating advanced materials, magnetic actuation and computational modelling. The work can be grouped into three main blocks.
1. Magneto-active materials and manufacturing: Ultra-soft magnetorheological elastomers (MREs) and biologically derived magneto-active hydrogels were developed and comprehensively characterised under combined mechanical and magnetic loading, providing the most extensive dataset to date for such systems. These studies revealed previously unknown viscoelastic and magnetic-history effects arising from field-induced microstructural rearrangements, leading to enhanced and complex macroscopic responses. The project also introduced hybrid MREs, combining soft- and hard-magnetic particles to achieve both strong magnetorheological effects and remanent magnetisation. In parallel, a novel 4D printing strategy based on custom-designed direct ink writing hardware and software enabled the fabrication of multidomain and multimaterial magneto-active structures using reactive inks without chemical additives.
2. Modelling and optimisation frameworks: New constitutive and computational frameworks were developed to describe magneto-mechanical coupling, viscoelasticity and magnetic-history effects across multiple length scales, explicitly accounting for magnetic sources and surrounding media. In addition, topology and multimaterial optimisation tools were created to design structures with targeted magneto-mechanical responses. These models were validated against experiments and used to guide material design, manufacturing strategies and actuation protocols, with several tools released as open-source software.
3. Magneto-mechanical platform for mechanobiology: The central outcome of the project is a novel experimental-computational platform enabling remote, non-invasive, reversible and dynamically programmable control of complex deformation patterns in cellular and tissue substrates. The platform was successfully applied to study mechanotransduction in brain cells, cancer models and three-dimensional hydrogels, demonstrating how controlled mechanical cues regulate cellular structure and function, supported by dedicated computational models for experimental design and interpretation.
*Exploitation and dissemination: Project results have been disseminated through high-impact publications, invited talks and open-source software. Key technological outcomes were protected by patents and recognised through innovation programmes, leading to two ERC Proof of Concept grants, an EIC Transition project and the creation of the spin-off 60Nd S.L. which is commercialising the developed technology. The project was also actively communicated to society through press releases, media interviews, laboratory open days and outreach activities.
1. Magneto-active materials and manufacturing: Ultra-soft magnetorheological elastomers (MREs) and biologically derived magneto-active hydrogels were developed and comprehensively characterised under combined mechanical and magnetic loading, providing the most extensive dataset to date for such systems. These studies revealed previously unknown viscoelastic and magnetic-history effects arising from field-induced microstructural rearrangements, leading to enhanced and complex macroscopic responses. The project also introduced hybrid MREs, combining soft- and hard-magnetic particles to achieve both strong magnetorheological effects and remanent magnetisation. In parallel, a novel 4D printing strategy based on custom-designed direct ink writing hardware and software enabled the fabrication of multidomain and multimaterial magneto-active structures using reactive inks without chemical additives.
2. Modelling and optimisation frameworks: New constitutive and computational frameworks were developed to describe magneto-mechanical coupling, viscoelasticity and magnetic-history effects across multiple length scales, explicitly accounting for magnetic sources and surrounding media. In addition, topology and multimaterial optimisation tools were created to design structures with targeted magneto-mechanical responses. These models were validated against experiments and used to guide material design, manufacturing strategies and actuation protocols, with several tools released as open-source software.
3. Magneto-mechanical platform for mechanobiology: The central outcome of the project is a novel experimental-computational platform enabling remote, non-invasive, reversible and dynamically programmable control of complex deformation patterns in cellular and tissue substrates. The platform was successfully applied to study mechanotransduction in brain cells, cancer models and three-dimensional hydrogels, demonstrating how controlled mechanical cues regulate cellular structure and function, supported by dedicated computational models for experimental design and interpretation.
*Exploitation and dissemination: Project results have been disseminated through high-impact publications, invited talks and open-source software. Key technological outcomes were protected by patents and recognised through innovation programmes, leading to two ERC Proof of Concept grants, an EIC Transition project and the creation of the spin-off 60Nd S.L. which is commercialising the developed technology. The project was also actively communicated to society through press releases, media interviews, laboratory open days and outreach activities.
4D-BIOMAP has significantly advanced the state of the art in mechanobiology and smart materials by overcoming long-standing limitations in the control and reproduction of mechanical environments in biological systems. Prior to this project, most experimental platforms relied on static, contact-based or geometrically constrained mechanical stimulation, severely limiting the complexity and physiological relevance of in vitro models. The project introduced a fundamentally new approach based on magneto-active materials and remote magnetic actuation, enabling non-invasive, reversible and dynamically programmable mechanical stimulation. This represents a clear step beyond existing technologies by allowing complex combinations of deformation modes, spatial heterogeneity and temporal evolution to be applied without physical contact. In addition, the development of ultra-soft magneto-active materials and biologically derived hydrogels extended these capabilities to mechanically realistic regimes relevant for soft tissues and three-dimensional culture systems. From a materials and modelling perspective, 4D-BIOMAP went beyond the state of the art by identifying and exploiting magnetic-history and viscoelastic mechanisms that were previously unknown in ultra-soft magnetorheological systems. The project also delivered new computational frameworks that explicitly account for magnetic sources and surrounding media, enabling quantitative predictions that were not achievable with conventional modelling approaches.
By the end of the project, these advances have converged into a validated experimental-computational platform that enables mechanobiological studies under physiologically and pathologically relevant mechanical conditions. The expected results at the conclusion of the action include: (i) a robust and transferable technology for remote mechanical stimulation of cells and tissues; (ii) a new class of multifunctional magneto-active materials and hydrogels; (iii) predictive modelling tools to guide experimental design; and (iv) proof-of-concept biological studies demonstrating the impact of controlled mechanics on cellular function. Together, these results establish a new technological and conceptual framework that goes well beyond the prior state of the art, providing a foundation for more predictive biomedical models, novel therapeutic strategies and the emergence of mechanomedicine as a distinct research and innovation field.
By the end of the project, these advances have converged into a validated experimental-computational platform that enables mechanobiological studies under physiologically and pathologically relevant mechanical conditions. The expected results at the conclusion of the action include: (i) a robust and transferable technology for remote mechanical stimulation of cells and tissues; (ii) a new class of multifunctional magneto-active materials and hydrogels; (iii) predictive modelling tools to guide experimental design; and (iv) proof-of-concept biological studies demonstrating the impact of controlled mechanics on cellular function. Together, these results establish a new technological and conceptual framework that goes well beyond the prior state of the art, providing a foundation for more predictive biomedical models, novel therapeutic strategies and the emergence of mechanomedicine as a distinct research and innovation field.