Multilevel Assessment of Stent-Induced Inflammation in the Adjacent Vascular Tissue

A recent U.S. Foodand Drug Administration report presentedthecurrently available scientific information related to biologicalresponse to metal implants. In this work, a multilevel approach wasemployed to assess the implant-induced and biocorrosion-related inflammationin the adjacent vascular tissue using a mouse stent implantation model.The implications of biocorrosion on peri-implant tissue were assessedat the macroscopic level via in vivo imaging andhistomorphology. Elevated matrix metalloproteinase activity, colocalizedwith the site of implantation, and histological staining indicatedthat stent surface condition and implantation time affect the inflammatoryresponse and subsequent formation and extent of neointima. Hematologicalmeasurements also demonstrated that accumulated metal particle contaminationin blood samples from corroded-stetted mice causes a stronger immuneresponse. At the cellular level, the stent-induced alterations inthe nanostructure, cytoskeleton, and mechanical properties of circulatinglymphocytes were investigated. It was found that cells from corroded-stentedsamples exhibited higher stiffness, in terms of Young's modulusvalues, compared to noncorroded and sham-stented samples. Nanomechanicalmodifications were also accompanied by cellular remodeling, throughalterations in cell morphology and stress (F-actin) fiber characteristics.Our analysis indicates that surface wear and elevated metal particlecontamination, prompted by corroded stents, may contribute to theinflammatory response and the multifactorial process of in-stent restenosis.The results also suggest that circulating lymphocytes could be a novelnanomechanical biomarker for peri-implant tissue inflammation andpossibly the early stage of in-stent restenosis. Large-scale studiesare warranted to further investigate these findings.

Automated summary

A recent FDA report examined the scientific information on the biological response to metal implants. Using a mouse stent implantation model, the study found that surface condition and implantation time affected the inflammatory response and subsequent formation of neointima. It also indicated that elevated metal particle contamination in corroded-stent samples caused a stronger immune response.