"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 Orthopaedic 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."

In humans, tissues like cartilage can often break down, causing joint instability or pain. Often, the breakdown isn't in total, but covers an area, forming a hole. Current fixes are to 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. It's 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 eventually wear away with use because it's not the same material and can't bond the same way.

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 Orthopaedic Surgery and Bioengineering, sought to find a way to fix the potholes by repaving them instead of filling them 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.

Co-authors on this study included Sarah Gullbrand and James Carey of the University of Pennsylvania and Andy Clark and Xuemei Cheng of Bryn Mawr College.

Financial support was provided by the National Institutes of Health (grant numbers R01 AR056624, R01 AR071340, T32 AR007132, and P30 AR069619), the Department of Veteran Affairs (IK6 RX003416) and the National Sciences Foundation for Engineering Mechanobiology (CMMI: 15-48571).

Story Source:

Materials provided by University of Pennsylvania School of Medicine. Note: Content may be edited for style and length.

Journal Reference:

1. Hannah M. Zlotnick, Andy T. Clark, Sarah E. Gullbrand, James L. Carey, Xuemei M. Cheng, Robert L. Mauck. Magneto‐Driven Gradients of Diamagnetic Objects for Engineering Complex Tissues. Advanced Materials, 2020; 2005030 DOI: 10.1002/adma.202005030