HEPARIN AS AN ANTIBACTERIAL COATING ON BIODEGRADABLE URETERAL STENTS: EXPERIMENTAL STUDY OF BRAIDSTENT®-H

INTRODUCTION The aim of this study is to assess the effectiveness of heparin to inhibit the development of early bacteriuria as a coating for biodegradable ureteral stents. MATERIAL AND METHODS The BraidStent®-H biodegradable stent, whose heparin coating is incorporated by dip coating, was chosen for this study. Twenty-four swine were randomly divided into two groups: 12 animals underwent unilateral placement of the BraidStent®-H and 12 were fitted with a standard double-j stent (DJS). Bacteriuria is comparatively analyzed over time by consecutive urine sampling at 0, 1, 3, 6, 12, 24 and 48 hours. In addition, the concentration of heparin released in vitro in artificial urine at 0, 3, 6, 12, 24, 48, 72, 92 and 120 hours is determined via ELISA. RESULTS BraidStent®-H generates a significantly lower bacteriuria rate than a DJS at 6 and 12 hours. Heparin coating shows a significant delaying effect on the onset of bacteriuria, reaching 100% of the animals at 48 hours, compared to the DJS, which takes place at 6 hours. ELISA results reveal the presence of heparin in urine for a total of 72 hours. The coating does not affect the degradation of the device, which is completed at 6 weeks. CONCLUSIONS Heparin evidences an effective inhibition of early bacteriuria, showing its potential as an antibacterial coating for biodegradable ureteral stents. Future studies should focus on the development of long-term heparin coatings for biodegradable materials.

Comparative assessment of biodegradable-antireflux heparine coated ureteral stent: animal model study

Background Double J ureteral stents are widely used on urological patients to provide drainage of the upper urinary tract. Unfourtunately, ureteral stents are not free from complications, as bacterial colonization and require a second procedure for removal. The purpose of the current comparative experimental study is to evaluate a new heparin-coated biodegradable antireflux ureteral stent (BraidStent®-H) to prevent urinary bacterial colonization. Methods A total of 24 female pigs were underwent determination of bacteriuria and nephrosonographic, endoscopic and contrast fluoroscopy assessment of the urinary tract. Afterward, were randomly assigned animals to Group-I, in which a 5Fr double-pigtail ureteral stent was placed for 6 weeks, or Group-II, in which a BraidStent®-H was placed. Follow-up assessments were performed at 1, 3, 6, 8, 12 weeks. The final follow-up includes the above methods and an exhaustive pathological study of the urinary tract was accomplished after 20 weeks. Results Bacteriuria findings in the first 48 h were significant between groups at 6 h and 12 h. Asymptomatic bacteriuria does not reach 100% of the animals in Group-II until 48 h versus Group-I where it appears at 6 h. The weekly bacteriuria mean rate was 27.7% and 44.4% in Group I and II respectively, without statistical significance. In Group II there were no animals with vesicoureteral reflux, with statistical significance at 3 and 6 weeks with Group-I. The 91.2% of stents in Group-II were degraded between 3 and 6 weeks, without obstructive fragments. Distal ureteral peristalsis was maintained in 66.6–75% in Group-II at 1–6 weeks. Conclusions The heparin coating of BraidStent® allows an early decrease of bacterial colonization, but its effectiveness is low at the long term. Heparin coating did not affect scheduled degradation rate or size of stents fragments. BraidStent®-H avoids the side effects associated with current ureteral stents, thus should cause less discomfort to patients.

Endothelialization of an ePTFE vessel prosthesis modified with an antithrombogenic fibrin/heparin coating enriched with bound growth factors

A fibrin/heparin coating enriched with bound growth factors was developed and applied on an ePTFE vessel prosthesis. The coating exhibited excellent antithrombogenic properties and supported endothelialization of the ePTFE vessel.

A Novel C1-Esterase Inhibitor Oxygenator Coating Prevents FXII Activation in Human Blood

The limited hemocompatibility of currently used oxygenator membranes prevents long-term use of artificial lungs in patients with lung failure. To improve hemocompatibility, we developed a novel covalent C1-esterase inhibitor (C1-INH) coating. Besides complement inhibition, C1-INH also prevents FXII activation, a very early event of contact phase activation at the crossroads of coagulation and inflammation. Covalently coated heparin, as the current anticoagulation gold standard, served as control. Additionally, a combination of both coatings (C1-INH/heparin) was established. The coatings were tested for their hemocompatibility by dynamic incubation with freshly drawn human whole blood. The analysis of various blood and plasma parameters revealed that C1-INH-containing coatings were able to markedly reduce FXIIa activity compared to heparin coating. Combined C1-INH/heparin coatings yielded similarly low levels of thrombin-antithrombin III complex formation as heparin coating. In particular, adhesion of monocytes and platelets as well as the diminished formation of fibrin networks were observed for combined coatings. We could show for the first time that a covalent coating with complement inhibitor C1-INH was able to ameliorate hemocompatibility. Thus, the early inhibition of the coagulation cascade is likely to have far-reaching consequences for the other cross-reacting plasma protein pathways.

Heparinoid Complex-Based Heparin-Binding Cytokines and Cell Delivery Carriers

Heparinoid is the generic term that is used for heparin, heparan sulfate (HS), and heparin-like molecules of animal or plant origin and synthetic derivatives of sulfated polysaccharides. Various biological activities of heparin/HS are attributed to their specific interaction and regulation with various heparin-binding cytokines, antithrombin (AT), and extracellular matrix (ECM) biomolecules. Specific domains with distinct saccharide sequences in heparin/HS mediate these interactions are mediated and require different highly sulfated saccharide sequences with different combinations of sulfated groups. Multivalent and cluster effects of the specific sulfated sequences in heparinoids are also important factors that control their interactions and biological activities. This review provides an overview of heparinoid-based biomaterials that offer novel means of engineering of various heparin-binding cytokine-delivery systems for biomedical applications and it focuses on our original studies on non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) and polyelectrolyte complex-nano/microparticles (N/MPs), in addition to heparin-coating devices.