Scientists at the Perelman School of Medicine at the University of Pennsylvania used a magnetic field and hydrogels to demonstrate a new possible way to rebuild complex body tissues, which they say could result in more lasting fixes to common injuries, such as cartilage degeneration.

Their study “Magneto‐Driven Gradients of Diamagnetic Objects for Engineering Complex Tissues” appears in Advanced Materials.

“Engineering complex tissues represents an extraordinary challenge and, to date, there have been few strategies developed that can easily recapitulate native‐like cell and biofactor gradients in 3D materials. This is true despite the fact that mimicry of these gradients may be essential for the functionality of engineered graft tissues. Here, a non‐traditional magnetics‐based approach is developed to predictably position naturally diamagnetic objects in 3D hydrogels,” write the investigators.

“Rather than magnetizing the objects within the hydrogel, the magnetic susceptibility of the surrounding hydrogel precursor solution is enhanced. In this way, a range of diamagnetic objects (e.g., polystyrene beads, drug delivery microcapsules, and living cells) are patterned in response to a brief exposure to a magnetic field. Upon photo‐crosslinking the hydrogel precursor, object positioning is maintained, and the magnetic contrast agent diffuses out of the hydrogel, supporting long‐term construct viability.”

“This approach is applied to engineer cartilage constructs with a depth‐dependent cellularity mirroring that of native tissue. These are thought to be the first results showing that magnetically unaltered cells can be magneto‐patterned in hydrogels and cultured to generate heterogeneous tissues. This work provides a foundation for the formation of opposing magnetic‐susceptibility‐based gradients within a single continuous material.”

“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, Hannah Zlotnick, a graduate student in bioengineering who works in the McKay Orthopedic Research Laboratory at Penn Medicine. “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.”

Current fixes for tissue breakdown like cartilage are to fill 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. What complicates fixing cartilage or other similar tissues is that their make-up is complex.

“There is a natural gradient from the top of cartilage to the bottom, where it contacts the bone,” Zlotnick explained. “Superficially, or 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.”

So the researchers, which included senior author Robert Mauck, PhD, director of the McKay Lab and a professor of orthopedic surgery and bioengineering, sought to find a way to fix tissue damage by repaving it instead of filling it in. With that in mind, the research team 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 the objects in it) was exposed to ultraviolet light in a process called “photo crosslinking” to lock everything in place, and the magnetic solution subsequently was diffused out. After this, the engineered tissues maintained the necessary cellular gradient.

With this magneto-patterning technique, the team was able to recreate 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 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, it’s the first step toward potential 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,” Mauck explained.

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