Facial nerve accidents are sometimes handled with tissue taken from a affected person’s physique, referred to as autografts. Alternatively, researchers are growing engineered conduits which might probably be extra accessible. Credit score: NIBIB. Created with BioRender.com
A gesture so simple as a smile can typically convey what phrases can not. That is a part of why nonverbal communication is so central to human interplay. It’s also why facial nerve problems and accidents could be devastating.
These situations are sometimes handled with nerve tissue taken from elsewhere in a affected person’s physique, often known as autografts. This system for repairing injured nerves presents points for sufferers, resembling harm to the donor web site and the percentages of practical restoration being almost a coin toss. Artificial options have been explored prior to now however have but to stay as much as the efficiency of autografts.
Bioengineers on the College of Pittsburgh might have developed a brand new resolution with the assistance of a few of nature’s finest engineers—stem cells. Leveraging these cells’ skill to create a restorative surroundings, the workforce produced implantable conduits to behave as bridges, offering directional, mechanical, and biochemical steerage for injured nerves to regenerate throughout massive gaps.
Experiments within the facial nerves of rats confirmed that the know-how matched autografts. These outcomes have been revealed within the Journal of Neural Engineering.
“We leaned into the idea that the cells know what they’re doing, and they know how to make tissue,” stated oral and craniofacial sciences and bioengineering professor Fatima Syed-Picard, Ph.D., the senior writer of the examine. “These engineered tissues ended up being more biomimetic than many other synthetically derived scaffolds used in tissue engineering.”
Getting neurons in line
For nerves to be repaired, the lengthy projections that stretch from neurons, referred to as axons, have to each regrow and reconnect to the suitable tissue. With autografts, the previous is sluggish, and the latter isn’t any assure, as many sufferers expertise undesirable muscle exercise as a result of regrown nerves connecting to the mistaken tissue.
The authors of the examine created their nerve conduits by rolling up cell-made sheets of extracellular matrix. Credit score: Journal of Neural Engineering (2024). DOI: 10.1088/1741-2552/ad749d
Researchers have wielded particular cell populations to speed up development, resembling neural assist cells and stem cells, which produce biomolecules that assist neural tissue regeneration. To orient rising tissue in order that axons attain the correct targets, researchers have designed artificial tissue scaffolds with options, resembling grooves, that act as guiderails to regenerating neurons.
“It’s difficult to embed and distribute cells evenly in synthetic scaffolds without harming them. Another concern is trying to get these scaffolds to match the structural complexity of innate tissue,” stated first writer Michelle Drewry, Ph.D., who carried out this analysis whereas a graduate scholar on the College of Pittsburgh.
Many cell sorts within the physique steadily make or transform the biomolecular scaffolding surrounding them, often known as extracellular matrix (ECM). So, as a substitute of creating tissue scaffolds from scratch themselves, the researchers thought it is perhaps higher to let cells make their very own.
The authors of the examine examined this speculation with dental pulp stem cells (DPSCs), a hardy and available cell inhabitants that produce proteins recognized to encourage nerve development. After extracting these cells from grownup knowledge tooth offered by the College of Pittsburgh Faculty of Dental Medication, the researchers put them to work.
They needed to provide DPSCs the liberty to create ECM however, on the identical time, nudge them into making an surroundings conducive to supporting aligned axons. To perform this, the researchers fabricated rubber molds with rows of 10 micrometer-wide grooves after which coated them with DPSCs. After a number of days, the DPSCs secreted aligned ECM round themselves, forming skinny organic sheets. The authors then peeled the sheets from the rubber templates and rolled them up into cylindrical conduits.
The researchers used this strategy to make a sort of bandage in a earlier examine, which efficiently regenerated the axons of a crushed nerve. With their new work, they sought to clear a better hurdle of utilizing the conduit to bridge a 5-millimeter hole within the facial nerve of rats—a defect so massive that the nerve wouldn’t be capable of heal by itself.
Particularly, they implanted their aligned conduits into gaps made within the buccal department of the facial nerve. For comparability, the workforce additionally implanted autografts into one other group of rats.
To substantiate that their nerve conduits contained aligned grooves to information nerve regeneration, the researchers used scanning electron microscopy. Credit score: Journal of Neural Engineering (2024). DOI: 10.1088/1741-2552/ad749d
“The buccal branch is the part of the facial nerve that helps with smiling. It’s a big part of your quality of life because it’s a large piece of how you communicate with other people and how you’re seen in the world. Injury to that nerve can have a life-changing effect,” Drewry stated.
Crossing the bridge
Twelve weeks after implantation, the authors evaluated how properly axons had regenerated, primarily by means of histology. They discovered that their cell-made conduits contained regenerated axons throughout their full size. And, generally, the density and variety of axons have been much like what they present in autografts.
Indicators of growing axons have been prevalent within the conduits, suggesting that regeneration might have been extra strong with further time, Drewry famous.
However did all this regenerated tissue translate to improved operate? To search out out, the authors electrically stimulated the nerves on one finish and measured the animals’ whisker motion on the opposite aspect. The checks confirmed that the motions of rats implanted with conduits have been on par with these handled with autografts.
Syed-Picard’s lab goals to raised perceive the roles the ECM and cells play in therapeutic after which use that info to enhance their know-how. For instance, along with encouraging regrowth instantly, the conduits may additionally be serving to by dampening irritation, Syed-Picard defined.
Extra info:
Michelle D Drewry et al, Enhancing facial nerve regeneration with scaffold-free conduits engineered utilizing dental pulp stem cells and their endogenous, aligned extracellular matrix, Journal of Neural Engineering (2024). DOI: 10.1088/1741-2552/ad749d
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Engineering a smile: Stem cell–based mostly conduits restore facial nerve operate in animal examine (2024, December 24)
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