Hydrogel-based scaffolds may very well be used for higher brain-computer interfaces — ScienceDaily

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Mind-computer interfaces (BCIs) are a scorching matter today, with corporations like Neuralink racing to create gadgets that join people’ brains to machines by way of tiny implanted electrodes. The potential advantages of BCIs vary from improved monitoring of mind exercise in sufferers with neurological issues to restoring imaginative and prescient in blind folks to permitting people to manage machines utilizing solely our minds. However a significant hurdle for the event of those gadgets is the electrodes themselves — they have to conduct electrical energy, so almost all of them are made from metallic. Metals usually are not essentially the most brain-friendly supplies, as they’re arduous, inflexible, and do not replicate the bodily atmosphere through which mind cells sometimes develop.

That drawback now has an answer in a brand new sort of electrically conductive hydrogel scaffold developed on the Wyss Institute at Harvard College, Harvard’s John A. Paulson Faculty of Engineering and Utilized Sciences (SEAS), and MIT. Not solely does the scaffold mimic the delicate, porous circumstances of mind tissue, it supported the expansion and differentiation of human neural progenitor cells (NPCs) into a number of completely different mind cell sorts for as much as 12 weeks. The achievement is reported in Superior Healthcare Supplies.

“This conductive, hydrogel-based scaffold has nice potential. Not solely can or not it’s used to check the formation of human neural networks in vitro, it might additionally allow the creation of implantable biohybrid BCIs that extra seamlessly combine with a affected person’s mind tissue, bettering their efficiency and reducing danger of damage,” stated first writer Christina Tringides, Ph.D., a former graduate pupil on the Wyss and SEAS who’s now a Postdoctoral Fellow at ETH Zürich.

Out of 1, many

Tringides and her staff created their first hydrogel-based electrode in 2021, pushed by the will to make softer electrodes that might “movement” to hug the mind’s pure curves, nooks, and crannies. Whereas the staff demonstrated that their electrode was extremely appropriate with mind tissue, they knew that essentially the most appropriate substance for residing cells is different cells. They determined to attempt to combine residing mind cells into the electrode itself, which might probably permit an implanted electrode to transmit electrical impulses to a affected person’s mind by way of extra pure cell-cell contact.

To make their conductive hydrogel a extra snug place for cells to stay, they added a freeze-drying step to the manufacturing course of. The ice crystals that fashioned in the course of the freeze-drying compelled the hydrogel materials to pay attention within the areas across the crystals. When the ice crystals evaporated, they left behind pores surrounded by the conductive hydrogel, forming a porous scaffold. This construction ensured that cells would have ample floor space on which to develop, and that the electrically conductive parts would kind a steady pathway by way of the hydrogel, delivering impulses to all of the cells.

The researchers different the recipes of their hydrogels to create scaffolds that had been both viscoelastic (like Jell-O) or elastic (like a rubber band) and delicate or stiff. They then cultured human neural progenitor cells (NPCs) on these scaffolds to see which mixture of bodily properties finest supported neural cell progress and growth.

Cells grown on gels that had been viscoelastic and softer fashioned networks of lattice-like buildings on the scaffold and differentiated into a number of different cell sorts after 5 weeks. Cells that had been cultured on elastic gels, in distinction, had fashioned clumps that had been largely composed of undifferentiated NPCs. The staff additionally different the quantity of conductive supplies throughout the hydrogel materials to see how that affected neural progress and growth. The extra conductive a scaffold was, the extra the cells fashioned branching networks (as they do in vivo) reasonably than clumps.

The researchers then analyzed the completely different cell sorts that had developed inside their hydrogel scaffolds. They discovered that astrocytes, which assist neurons each bodily and metabolically, fashioned their attribute lengthy projections when grown on viscoelastic gels vs. elastic gels, and there have been considerably extra of them current when the viscoelastic gels contained extra conductive materials. Oligodendrocytes, which create the myelin sheath that insulates the axons of neurons, had been additionally current within the scaffolds. There was extra whole myelin and longer myelinated segments on viscoelastic gels than on elastic gels, and the thickness of the myelin elevated when there was extra conductive materials current within the gels.

The pièce de (electrical) résistance

Lastly, the staff utilized electrical stimulation to the residing human cells by way of the conductive supplies inside their hydrogel scaffold to see how that impacted cell progress. The cells had been pulsed with electrical energy for quarter-hour at a time, both every day or each different day. After eight days, the scaffolds that had been pulsed every day had only a few residing cells, whereas those who had been pulsed each different day had been filled with residing cells all through the scaffold.

Following this stimulation interval, the cells had been left within the scaffolds for a complete of 51 days. The few cells left within the scaffolds that had been stimulated every day didn’t differentiate into different cell sorts, whereas the every-other-day scaffolds had extremely differentiated neurons and astrocytes with lengthy protrusions. The variation in electrical impulses examined didn’t appear to affect the quantity of myelin current within the gels.

“The profitable differentiation of human NPCs into a number of forms of mind cells inside our scaffolds is affirmation that the conductive hydrogel gives them the proper of atmosphere through which to develop in vitro,” stated senior writer Dave Mooney, Ph.D., a Core College member on the Wyss Institute. “It was particularly thrilling to see myelination on the neurons’ axons, as that has been an ongoing problem to duplicate in residing fashions of the mind.” Mooney can also be the Robert P. Pinkas Household Professor of Bioengineering at SEAS.

Tringides is continuous work on the conductive hydrogel scaffolds, with plans to additional examine how numerous forms of electrical stimulation might have an effect on completely different cell sorts, and to develop a extra complete in vitro mannequin. She hopes that this expertise will someday allow the creation of gadgets that assist restore perform in human sufferers who’re affected by neurological and physiological issues.

“This work represents a significant advance by creating an in vitro microenvironment with the best bodily, chemical, and electrical properties to assist the expansion and specialization of human mind cells. This mannequin could also be used to hurry up the method of discovering efficient remedies for neurological ailments, along with opening up a wholly new strategy to create simpler electrodes and brain-machine interfaces that seamlessly combine with neuronal tissues. We’re excited to see the place this modern melding of supplies science, biomechanics, and tissue engineering leads sooner or later,” stated the Wyss Institute’s Founding Director Don Ingber, M.D., Ph.D. Ingber can also be the Judah Folkman Professor of Vascular Biology at Harvard Medical Faculty and Boston Youngsters’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at SEAS.

Extra authors embody Marjolaine Boulingre from SEAS, Andrew Khalil from the Wyss Institute and the Whitehead Institute at MIT, Tenzin Lungjangwa from the Whitehead Institute, and Rudolf Jaenisch from the Whitehead Institute and MIT.

This work was supported by the Nationwide Science Basis beneath award nos. 1541959 and DMR-1420570 and a Graduate Analysis Fellowship Program grant, NIH grants RO1DE013033 5R01DE013349, NSF-MRSEC DMR-2011754, the Wyss Institute for Biologically Impressed Engineering at Harvard College, the EPFL WISH Basis, and the Wellcome Leap HOPE mission.

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