Blocking molecules protects health of implants

Blocking a key molecule protects breast implants, permanent catheters, pacemakers, artificial joints, glucose sensors for diabetics, and other biomaterials from rejection and damage by the body, according to a study published this month in The American Journal of Pathology.

The more complicated the function of the implant, the more likely it is to be rendered non-functional due to damage induced by the body, said the lead author, Themis Kyriakides, assistant professor of pathology and a member of the interdepartmental program in Vascular Biology and Transplantation at Yale School of Medicine.

“Implantation of biomaterials and tissue-engineered devices into tissues cause the development of a foreign body reaction that can lead to implant failure,” Kyriakides said. “The foreign body reaction has been implicated in the malfunction and failure of numerous devices and implants.”

Kyriakides and his colleagues focused on the area of contact between the tissue and the implant, or biomaterial, where foreign body giant cells are formed from the fusion of recruited inflammatory cells that attack the implant. The CC chemokine ligand (CCL)-2, previously known as monocyte chemoattractant protein (MCP)-1, is believed to be responsible for the recruitment of foreign body giant cell precursors to the implant site. This study examined what would happen if the expression or function of CCL2 was eliminated both in mice genetically engineered without the molecule and in other mice where the function of CCL2 was blocked by means of a protein decoy via localized gene delivery.

“What we found is that in the absence of CCL2 these large cells do not form at the site of the implant, therefore protecting the implant from damage,” Kyriakides said. He said the significance of the finding is discovering a new and more complex role for CCL2 in the foreign body response. The success at blocking the CCL2 in mice using a protein decoy also paves the way for a therapeutic drug target to help sustain implants.

Co-authors include Matt Foster, Grant Keeney, Annabel Tsai, Cecilia Giachelli and Paul Bornstein, all of the University of Washington, Ian Clark-Lewis of the University of British Columbia in Vancouver, Canada, and Barrett Rollins of Harvard.