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Microchannels for controlling cellular mechanotransduction

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A novel microstructured hydrogel with unique antimicrobial properties

Porous scaffolds offer a 3D extracellular environment similar to the cell’s natural environment and their application in regenerative medicine is immense. EU researchers have developed a novel biomaterial to support cell differentiation and restore damaged tissue.

Health

Through mechanical stimuli the extracellular environment determines cell behaviour and processes such as adhesion, proliferation, migration and differentiation. Materials science tries to mimic the structural, mechanical and biochemical properties of the natural extracellular matrix to maximise regeneration of damaged tissue via spatially organised cell growth.

A novel biomaterial with a microchannel network

The EU-funded CHANNELMAT project developed a novel 3D material that is inexpensive and biocompatible for use as a scaffold for cell growth. As project coordinator Christine Selhuber-Unkel explains “our material contains hollow channels of a few microns in size embedded in a polymer matrix.″ This provides a large surface area for cell contact, maximising the influence of the material on cell behaviour, for example for controlling the transduction of mechanical stimuli. Compared to existing solutions, the CHANNELMAT approach offers various advantages. It uses a polyacrylamide substrate to produce interconnected microchannels with a diameter smaller than 20 μm. The patented fabrication procedure ensures pore interconnectivity independent of pore density and size. Importantly, the fine microchannels provide a 3D environment with up to 80 % contact with the cell surface, which enhances control of cell behaviour. Tailoring the design, composition and mechanics of the scaffold ensures that oxygen and nutrient provision closely resemble the conditions of natural tissues. Moreover, the scaffold can be functionalised with proteins for tissue engineering and with carbon-based nanoparticles for mimicking electrically excitable tissue such as heart tissue, while its strong adsorption of proteins means that it can be designed to resemble the extracellular matrix.

Medical applications of the novel material

“Our goal was to validate the CHANNELMAT novel material in cellular applications where mechanotransduction is affected, such as in the cardiac tissue after a heart attack,″ continues Selhuber-Unkel. The well-defined mechanical properties of the biomaterial and the capacity to fabricate it with different levels of complexity in a high-throughput manner render it suitable for numerous applications such as 3D cell cultures and implantation. Nonetheless, the most important clinically relevant finding is currently independent of mechanotransduction. The scientific team has employed the innovative material for capturing the human pathogen Acanthamoeba castellanii. Known for its capacity to infect the eye and cause severe keratitis, the treatment is prolonged and complex. Despite the rarity of the disease, it is a particularly prevalent problem in developed countries where contact lens usage is common. Moreover, Acanthamoeba castellanii is encountered in both soil and water reservoirs including swimming pools and contact lens liquids despite disinfection. The CHANNELMAT material has the potential to remove the parasite Acanthamoeba castellanii and improve the safety of contact lenses if used in storage devices. According to Selhuber-Unkel, this was the most significant achievement of the project, which has opened new avenues for the commercial exploitation of the CHANNELMAT biomaterial. Capturing pathogenic microorganisms through fabricated traps is an emerging chemical-free antimicrobial strategy. Currently, researchers are investigating the materials in different contexts ranging from applications in the brain to soft robotics. Several funded projects build on the knowledge gained during CHANNELMAT, and with the appropriate industrial investment, they hope to take their product to the next level.

Keywords

CHANNELMAT, biomaterial, scaffold, mechanotransduction, Acanthamoeba castellanii, pathogen, hydrogel

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