rifampin and Thrombosis

Cardiovascular diseases constitute a number of conditions which are the leading cause of death globally. To combat these diseases and improve the quality and duration of life, several cardiac implants have been developed, including stents, vascular grafts and valvular prostheses. The implantation of these vascular prosthesis has associated risks such as infection or blood clot formation. In order to overcome these limitations medicated vascular prosthesis have been previously used. The present paper describes a 3D printing method to develop medicated vascular prosthesis using fused deposition modelling (FDM) technology. For this purpose, rifampicin (RIF) was selected as a model molecule as it can be used to prevent vascular graft prosthesis infection. Thermoplastic polyurethane (TPU) and RIF were combined using hot melt extrusion (HME) to obtain filaments containing RIF concentrations ranging between 0 and 1% (w/w). These materials are capable of providing RIF release for periods ranging between 30 and 80 days. Moreover, TPU-based materials containing RIF were capable of inhibiting the growth of Staphylococcus aureus. This behaviour was observed even for TPU-based materials containing RIF concentrations of 0.1% (w/w). TPU containing 1% (w/w) of RIF showed antimicrobial properties even after 30 days of RIF release. Alternatively, these methods were used to prepare dipyridamole containing TPU filaments. Finally, using a dual extrusion 3D printer vascular grafts containing both drugs were prepared.

Topics: Anti-Bacterial Agents; Blood Cells; Blood Vessel Prosthesis; Delayed-Action Preparations; Dipyridamole; Drug Delivery Systems; Drug Liberation; Equipment Design; Human Umbilical Vein Endothelial Cells; Humans; Platelet Aggregation Inhibitors; Polyurethanes; Printing, Three-Dimensional; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Technology, Pharmaceutical; Thrombosis

Despite refinements in surgical techniques, routine antibioprophylaxis, and anesthesiology, vascular prosthetic infections remain a serious complication of reconstructive vascular surgery. The purpose of this study was to evaluate the healing, the toxicity, and the antibiotic delivery of a new vascular graft, preloaded with rifampin and tobramycin. Sixteen dogs underwent infrarenal aortic bypass. They were divided into three groups. In test group 1 (n = 8), dogs received grafts loaded with a standard concentration of antibiotics. In test group 2 (n = 4), dogs received grafts loaded with twice the standard concentration of antibiotics. A control group (n = 4) received a commercial gelatin-sealed graft. Grafts were harvested after different periods of time and submitted to histological evaluation and antibiotic dose determination. Liver and kidney toxicities were evaluated from dosages performed on serum samples taken at different time periods between graft implantation and harvesting. The healing of antibiotic-loaded grafts was similar to that of commercial grafts, without any signs of toxicity. These results suggest resistance to infection of these prebonded grafts in an animal model.

Topics: Animals; Anti-Bacterial Agents; Aorta, Abdominal; Biocompatible Materials; Blood Vessel Prosthesis; Dogs; Gelatin; Giant Cells; Kidney; Liver; Male; Models, Animal; Polyesters; Prosthesis Design; Prosthesis-Related Infections; Rifampin; Surface Properties; Thrombosis; Time Factors; Tobramycin; Tunica Intima; Wound Healing

Topics: Female; Humans; Leg Ulcer; Male; Placental Extracts; Rifampin; Thrombosis; Varicose Veins