4D-BIOMAP

Smart materials for mechanobiology

The mechanical environment around cells has a significant influence on their behaviour. Researchers in the 4D-BIOMAP project are developing smart materials that change shape and stiffness when a magnetic field is applied, alongside investigating the impact of mechanical changes on cell behaviour, as Dr Daniel Garcia-Gonzalez explains.

The surrounding mechanical

environment has an important influence on the behaviour of cells and the way that they perform biological processes. Much like a human being, a cell will perform its activities more effectively and efficiently within a comfortable mechanical environment, which then helps the body to grow and repair itself. “The nature of the mechanical environment is important in terms of wound healing for example,” outlines Dr Daniel Garcia-Gonzalez, a research fellow at Universidad Carlos III de Madrid. As part of the ERC-backed 4D-BIOMAP project, Dr Garcia-Gonzalez is working to develop 3D printed composite materials that can reproduce the biological mechanical environment: from the comfort of healthy tissue to the mechanical disruptions that arise in events such as traumatic brain injury. “We are creating materials that respond, mechanically, to external magnetic fields,” he explains. “So basically we can apply an external magnetic field to these materials – in a remote and non-invasive fashion – and they will change their stiffness and shape, to take one example.”

Magneto-mechanical stimulator system for biological research

4D-BIOMAP project

Researchers in the project are working to develop these smart materials, called magneto-active polymers (MAPs), to serve as a substrate for cells. The ultimate aim is to effectively modify cell behaviour in the body using magnetic fields, depending on the needs of an individual patient. “We initially thought that these materials would mainly open research possibilities for neurological applications like traumatic brain injury, but now it is becoming apparent that they have more general potential, and can be applied in many different fields,” says Dr GarciaGonzalez. The materials themselves are elastomers with 2D cell cultures on top, which can be induced to change their shape when a magnetic field is applied. “The magnetic field activates a mechanical deformation on the substrate. This mechanical force, from the substrate, is then transmitted to the cells,” explains Dr Garcia-Gonzalez. “We can apply a given stress level, without needing to physically touch the cells. A non-invasive method minimises any interference with the cell’s physiological processes.”

The system developed by these researchers allows scientists to generate different magnetic conditions on the substrate. These magnetic fields can create highly complex deformation patterns within such a substrate, mimicking relevant biological scenarios. Alongside developing the smart materials, Dr Garcia-Gonzalez and his colleagues are also investigating how these changes affect the mechanical behaviour of cells. “We are looking to transmit these different forces to cells, in

order to understand how they behave,” he outlines. The project’s overall agenda combines computational, theoretical and experimental research, aiming to provide novel experimental-computational systems to control changes to the substrate and understand how they affect cells. “By playing with relative positions of permanent magnets, you change the magnetic fields, and the deformation of the material,” continues Dr Garcia-Gonzalez. “With our framework, we can see how this deformation is transmitted to the cells, and we can then see how the cells orient themselves, how they proliferate, and how certain signals are changed.”

This system could be applied in labs across different industries, an issue that Dr Garcia-Gonzalez plans to explore in the project. Current approaches to evaluating biomechanical effects are relatively limited; by contrast the 4D-BIOMAP system allows

The project is about more than developing a specific solution, or analysing a specific problem. We aim to provide new methodologies and novel

systems, which will open up new opportunities for people working in the mechanobiology field.

researchers to combine different mechanical inputs. “You can change the frequency of a cyclic loading for example, while changing the direction. The system allows you to reconstruct this complex mechanical environment around cells,” says Dr GarciaGonzalez. The pharmaceutical industry is one area that could benefit from the system, as it would help provide a deeper picture of the effectiveness of a drug, believes Dr Garcia-Gonzalez. “For example, with this system you can take mechanical forces into account when you are testing a drug treatment,” he points out. “We are providing people who investigate areas like cancer or the electrophysiology of neurons with an in vitro experimental framework to control the mechanical environment.”

Prototype

An initial prototype of the entire system has been developed, while Dr Garcia-Gonzalez is also working on several other strands of research in the project. The elastomers, with the 2D cell cultures, have been characterised across different scales, and researchers are working on using this platform with 3D cell cultures. “With these elastomers we currently put the cells on top. Now we are considering other materials, and we are looking into using hydrogels, so that the cells can go inside, which would be a more realistic approach,” outlines Dr Garcia-Gonzalez. Computational models and theoretical formulations have also been developed to predict the behaviour of the smart materials and cells, while research continues in other areas. “Another important part of the project is our work in developing software and hardware for a new 3D printing technology, to manufacture these materials,” says Dr Garcia-Gonzalez. “We have gained a lot of very interesting results during the project.”

The intention now is to look towards the translation of this research, and to develop experimental tools that can be implemented in different labs. These various systems and methodologies would enable interesting new possibilities for scientists, believes Dr Garcia-

Gonzalez. “The project is about more than developing a specific solution, or analysing a specific problem. We aim to provide new methodologies and novel systems, which will open up new opportunities for people working in the mechanobiology field,” he says. In the long-term, this research could help clinicians effectively control cell behaviour in the body using mechanical stimuli, which would be relevant to the treatment of a variety of conditions. “Our research is relevant not only to neurological applications, but also in areas like wound healing and cancer treatment,” outlines Dr Garcia-Gonzalez

This depends first of all on a deeper understanding of the impact of mechanical changes, an issue central to Dr GarciaGonzalez’s work in the project. In the case of neurological applications, when an individual experiences an impact to the head, there is a physiological response to the mechanical impact. “We can look at how deformations in the brain evolve and then, by using our in vitro system, we can apply the same patterns and see what the cells do,” says Dr Garcia-Gonzalez.

Biomechanical Stimulation based on 4D Printed Magneto-Active Polymers Project Objectives

MAPs are polymer-based composites that respond to magnetic fields with large deformation or tuneable mechanical properties. 4D-BIOMAP aims to apply heterogeneous 3D printed MAPs as modifiable substrates to support biological structures which can have their deformation state and stiffness controlled by the external application of magnetic stimuli.

Project Funding

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the ERC Starting Grant Agreement No. 947723.

Project Collaborators

• Instituto Cajal from CSIC • École Polytechnique at Paris • Institut Pasteur at Paris • Johns Hopkins University • University of Texas at Austin • Swansea University • FAU Erlangen-Nuremberg.

Contact Details

Daniel Garcia-Gonzalez, Ph.D Talent Attraction Fellow from Comunidad de Madrid ERC StG Grantee, 4D-BIOMAP Department of Continuum Mechanics and Structural Analysis University Carlos III of Madrid T: +34 916246053 E: danigarc@ing.uc3m.es W: www.multibiostructures.com W: http://danielgarciagonzalez.com/

https://doi.org/10.1016/j.apmt.2022.101437 Daniel Garcia-Gonzalez, PhD

Daniel Garcia-Gonzalez got his PhD at UC3M. Then he moved to the University of Oxford as a postdoctoral researcher. Back at UC3M, he was awarded an ERC Starting Grant. He created the new MULTIBIOSTRUCTURES Lab that puts together computational and experimental facilities to address challenges in advanced multifunctional materials and mechanistically mediated biological processes.