Synergistic effects of a novel nanoporous stent coating and tacrolimus on intima proliferation in rabbits.

To overcome the problem of in-stent restenosis, the concept of local delivery of antiproliferative or immunosuppressive drugs has been introduced into interventional cardiology. Local drug delivery can be achieved by drug-eluting stents coated with polymer surfaces used for controlled drug release. However, several polymer coatings have shown an induction of inflammatory response and increased neointima formation. In the present study, the effect of a new inorganic ceramic nanoporous aluminum oxide (Al(2)O(3)) coating on neointima proliferation and its suitability as a carrier for the immunosuppressive drug tacrolimus have been investigated. 316 L stainless steel coronary stents were coated with a 500 nm thin nanoporous aluminum oxide layer. This ceramic nanolayer was used as a carrier for tacrolimus. Bare stents (n = 6), ceramic coated stents (n = 6), and ceramic coated stents loaded with 60 (n = 7) and 120 mug (n = 6) tacrolimus were implanted in the common carotid artery of New Zealand rabbits. The ceramic coating caused no significant reduction of neointimal thickness after 28 days. Loading the ceramic stents with tacrolimus led to a significant reduction of neointima thickness by 52% for 60 mug (P = 0.047) and 56% for 120 mug (P = 0.036) as compared to the bare stents. The ceramic coating alone as well as in combination with tacrolimus led to a reduced infiltration of lymphocytes and macrophages in the intima in response to stent implantation. Ceramic coating of coronary stents with a nanoporous layer of aluminum oxide in combination with tacrolimus resulted in a significant reduction in neointima formation and inflammatory response. The synergistic effects of the ceramic coating and tacrolimus suggest that this new approach may have a high potential to translate into clinical benefit.

Immuno-inflammatory tissue reaction to stainless-steel and titanium plates used for internal fixation of long bones.

The immuno-inflammatory responses to stainless-steel (21 implants in 20 patients) and titanium plates (22 implants in 20 patients) used in the treatment of long bone fractures were studied immunohistochemically. All fractures healed without complications. In the soft tissue adjacent to the surface of the implants a dark discolouration of the tissue was visible in 18/21 stainless-steel and 20/22 titanium plates. Tissue specimens of all patients contained positive staining for macrophages (CD68-positive cells). Serial sections showed that the majority of cells were found to express the HLA-DR molecule indicating their activation. Many of the macrophages were surrounded by clusters of T-lymphocytes (CD3-positive cells). 17 out of 21 steel specimens and 15 out of 22 titanium specimens showed the infiltration of moderate amounts of cytotoxic T-lymphocytes (CD8-positive cells). Moderate amounts of B-lymphocytes (CD79alpha positive cells) were evident in four patients with steel and six patients with titanium implants. The results of the present study clearly demonstrate the presence of a marked inflammation and tissue reaction in the soft tissue covering stainless-steel and titanium plates used for internal fixation of fractures of long bones independently from the material used.