Sometimes Bigger Is Better for Implants

Researchers are focusing on the size and shape of implantable devices to increase their chances of lasting longer in the body and avoid rejection. They wound up discovering that bigger implants performed better than smaller ones.

Kristopher Sturgis

Just shooting for biocompatibility isn't good enough any more. The human body treats implantable medical devices as foreign bodies, triggering an immune response that can ultimately be counterproductive from a therapeutic standpoint. Stent thrombosis and restenosis are two notable examples of this.

Over the years, the medical device industry has made strides in making devices smaller and less invasive.

But a surprising MIT study has found that a larger implantable spherical device fared better in mice than smaller spherical devices. The larger devices maintained their function more efficiently while avoiding the build up of scarred-tissue.

The spheres in the study measured 0.5 and 1.5 mm in diameter. They were implanted within the abdominal cavity of diabetic mice. Afterwards, the researchers tracked their ability to respond to changes in glucose levels. The devices prepared with smaller spheres were completely surrounded by scar tissue and failed after about a month, while the larger ones were not rejected and continued functioning for more than six months.

"It has been the prevailing theory for some time that less material would theoretically induce a lower magnitude host response," said Joshua Doloff, a postdoc researcher at MIT's Koch Institute for Medical Engineering and Science, and one of the lead authors on a paper outlining the team's work. "However, we seem to have identified a few more broadly applicable anecdotes regarding the physical characteristics of an implant."

The researchers' first inclination was to try to make the implants smaller. "But as we were doing this, we kind of realized that the smaller ones were having a more pronounced response," said Omid Veiseh, another Koch Institute postdoc and fellow lead author of the study. "Rejection is such a big barrier to the translation of these technologies, so this became an area where we focused our efforts on."

"We think generally for a lot of implants that people may put into the body, using this knowledge and this sort of engineered material can be very beneficial," Veiseh said.

The group continued to test the small and large spheres in nonhuman primates in an effort to better understand the immune system response, and found that the larger spheres maintained better results. The smaller spheres planted under the skin became engulfed in scar tissue after only two weeks, while the larger spheres remained clear of scar tissue for up to four weeks.

The results continued to favor the larger spheres even when the materials changed from alginate to stainless steel, glass, polystyrene, and polycaprolactone.

"The phenomenon that we observed and highlight in our study appears to be material-independent," Doloff said. "Thus, regardless of material-specific properties, the observed reduction in rejection response due to large diameter spheres has more to do with object size and shape."

The team believes that these findings could be applicable to other types of implantable devices, including drug-delivery vehicles, and sensors for glucose and insulin. Work that could go a long way toward improving implants that help patients treat diabetes and other diseases.

"This research has significantly improved the prospects of creating a working deliverable device," Doloff said. "Thankfully, we have made strides and are additionally following other engineering concepts and strategies to combine with increased sphere sizes, with the hope to eventually treat human patients for as a long a period of time as possible."

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