The technique from researchers at the University of Pennsylvania uses a magnetic field and hydrogels.
“We found that we were able to arrange objects, such as cells, in ways that could generate new, complex tissues without having to alter the cells themselves,” said the study's first author, bioengineer Hannah Zlotnick.
“Others have had to add magnetic particles to the cells so that they respond to a magnetic field, but that approach can have unwanted long-term effects on cell health. Instead, we manipulated the magnetic character of the environment surrounding the cells, allowing us to arrange the objects with magnets.”
In humans, tissues like cartilage can often break down, causing joint instability or pain. Often the breakdown is not complete, but it forms a hole in a particular area. Current fixes fill those holes in with synthetic or biologic materials, which can work but often wear away because they are not the same exact material as what was there before.
The researchers said the current methods are similar to fixing a pothole in a road by filling it with gravel and making a tar patch – the hole will be smoothed out but will eventually wear away with use, because it is not the same material and cannot bond in the same way.
Fixing cartilage and other similar tissues is complicated by their complex make-up.
“There is a natural gradient from the top of cartilage to the bottom, where it contacts the bone,” said Zlotnick. “At the surface, cartilage has a high cellularity, meaning there is a higher number of cells. But where cartilage attaches to the bone, deeper inside, its cellularity is low.”
To tackle the issue, the team set out to ‘repave the potholes instead of filling them in’. The researchers found that if they added a magnetic liquid to a three-dimensional hydrogel solution, cells and other non-magnetic objects including drug delivery microcapsules could be arranged into specific patterns that mimicked natural tissue through the use of an external magnetic field.
After brief contact with the magnetic field, the hydrogel solution and internal objects are exposed to ultraviolet light in a process called photo crosslinking, which locks everything in place. The magnetic solution is then diffused out, leaving engineered tissues with the necessary cellular gradient.
With the ‘magneto-patterning’ technique the team recreated articular cartilage, the tissue that covers the ends of bones.
“These magneto-patterned engineered tissues better resemble the native tissue, in terms of their cell disposition and mechanical properties, compared to standard uniform synthetic materials or biologics that have been produced,” said senior author Robert Mauck. “By locking cells and other drug delivering agents in place via magneto-patterning, we are able to start tissues on the appropriate trajectory to produce better implants for cartilage repair.”
While the technique was restricted to in vitro studies – outside of a living organism – the team said the work is a first step towards longer-lasting, more efficient fixes in living subjects.
“This new approach can be used to generate living tissues for implantation to fix localized cartilage defects, and may one day be extended to generate living joint surfaces,” said Mauck.
The research was published in Advanced Materials.
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