Urological Implants Research Articles

An Evaluation of Parylene Thin Films to Prevent Encrustation for a Urinary Bladder Pressure MEMS Sensor System.

Recent developments in urological implants have focused on preventive strategies to mitigate encrustation and biofilm formation. Parylene, a conformal, pinhole-free polymer coating, has gained attention due to its high biocompatibility and chemical resistance, excellent barrier properties, and low friction coefficient. This study aims to evaluate the effectiveness of parylene C in comparison to a parylene VT4 grade coating in preventing encrustation on a urinary bladder pressure MEMS sensor system. Additionally, silicon oxide (SiOx) applied as a finish coating was investigated for further improvements. An in vitro encrustation system mimicking natural urine flow was used to quantify the formation of urinary stones. These stones were subsequently analyzed using Fourier transform infrared spectrometry (FTIR). Encrustation results were then discussed in relation to coating surface chemical properties. Parylene C and VT4 grades demonstrated a very low encrustation mass, making them attractive options for encrustation prevention. The best performance was achieved after the addition of a hydrophilic SiOx finish coating on parylene VT4 grade. Parylene-based encapsulation proved to be an outstanding solution to prevent encrustation for urological implants.

Contact-Active Layer-by-Layer Grafted TPU/PDMS Blends as an Antiencrustation and Antibacterial Platform for Next-Generation Urological Biomaterials: Validation in Artificial and Human Urine.

Urinary tract infections and urinary encrustation impede the long-term clinical performance of urological implants and medical devices. Together, biofilm formation and encrustation constitute serious complications, driving the development of next-generation urological biomaterials. The currently available bioengineered solutions have limited success during long-term usage in the urinary environment. In addressing this unmet clinical challenge, contact-active, antiencrustation surface grafting were conceived onto a dynamically cross-linked polydimethylsiloxane (PDMS) modified thermoplastic polyurethane (TPU) blend using the layer-by-layer (LbL) assembly route. To the best of the authors' knowledge, the present study is the first to investigate the LbL grafting in developing an antiencrustation platform. These multilayered assemblies strategically employed covalent cross-linking and electrostatic interaction-assisted progressive depositions of branched polyethyleneimine and poly(2-ethyl-2-oxazoline). While polyethyleneimine conferred the contact-killing bactericidal activity, the much-coveted antiencrustation properties were rendered by incorporating a partially hydrolyzed derivative of poly(2-ethyl-2-oxazoline). The performance of the resultant surface-modified TPU/PDMS blends was benchmarked against the conventional urological alloplasts, in a customized lab-scale bioreactor-based dynamic encrustation study and in human urine. After 6 weeks of exposure to an artificial urine medium, simulating urease-positive bacterial infection, the surface-modified blends exhibited a remarkable ability to suppress Ca and Mg encrustation. In addition, these blends also displayed superior grafting stability and antibacterial efficacy against common uropathogens. As high as 4-fold log reduction in the planktonic growth of Gram-negative P. mirabilis and Gram-positive MRSA was recorded with the LbL platform vis-à-vis medical-grade TPU. In conjunction, the in vitro cellular assessment with human keratinocytes (HaCaT) and human embryonic kidney cells (HEK) established the uncompromised cytocompatibility of the multilayered grafted blends. Finally, the physiologically relevant functionality of the LbL grafting has been validated using clinical samples of human urine collected from 129 patients with a broad spectrum of disease conditions. The phase-I pre-clinical study, entailing 6 week-long incubation in human urine, demonstrated significantly improved encrustation resistance of the blends. The collective findings of the present work clearly establish the success of LbL strategies in the development of stable, multifunctional new-generation urological biomaterials.

Preventive effect of surface charge on encrustation of biodegradable ureteral stents

Prevention of encrustation on the surface has always been the biggest challenge for urological implants. In the field of ureteral stent design, biodegradability has attracted much attention in recent years, because biodegradable ureteral stents not only avoid secondary intervention, but also prevent encrustation due to surface renewal by degradation process. Furthermore, researches have focus on some surface parameters to provide guidance for the development of stent materials, such as hydrophilicity or surface charge. In this work, we synthesized two types of poly(ester-carbonate)s, poly(L-lactide-co-5-amino-1,3-dioxan-2-one) (P(LA-co-AC)) containing amino, and poly (L-lactide-co-5-methyl-5-carboxyl-1,3-dioxan-2-one) (P(LA-co-MCC)) containing carboxyl. Blending P(LA-co-AC) and P(LA-co-MCC) with poly(L-lactide-co-Ɛ-caprolactone) (PLACL) respectively, two types of ureteral stent materials were prepared. Due to the influence of ions formed by the dissociation of amino and carboxyl, two types of materials show differences in surface charge analyses. We further developed a dynamic urinary extracorporeal circulation (DUEC) system to assess in vitro encrustation of materials with different surface charges. The results of this comparative study identified that the materials with strong negative surface charge were most favorable for use as ureteral stent, and provided a new approach to surmount the problems faced by urological surgery which complied with the future trend of biodegradable ureteral stent design.

Interactive Effects of Copper-Doped Urological Implants with Tissue in the Urinary Tract for the Inhibition of Cell Adhesion and Encrustation in the Animal Model Rat.

The insertion of a ureteral stent provides acute care by restoring urine flow and alleviating urinary retention or dysfunction. The problems of encrustation, bacterial colonization and biofilm formation become increasingly important when ureteral stents are left in place for a longer period of time. One way to reduce encrustation and bacterial adherence is to modify the stent surface with a diamond-like carbon coating, in combination with copper doping. The biocompatibilities of the Elastollan® base material and the a-C:H/Cu-mulitilayer coating were tested in synthetic urine. The copper content in bladder tissue was determined by atomic absorption spectroscopy and in blood and in urine by inductively coupled plasma mass spectrometry. Encrustations on the materials were analyzed by scanning electron microscopy, energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. A therapeutic window for copper ions of 0.5–1.0 mM was determined to kill bacteria without affecting human urothelial cells. In the rat animal model, it was found that copper release did not reach toxic concentrations in the affecting tissue of the urinary tract or in the blood. The encrustation behavior of the surfaces showed that the roughness of the amorphous carbon layer with the copper doping is probably the causal factor for the higher encrustation.

Prevention of Encrustation on Ureteral Stents: Which Surface Parameters Provide Guidance for the Development of Novel Stent Materials?

Encrustations of ureteral stents are one of the biggest problems with urological implants. Crystalline biofilms can occur alone or in combination with bacterial biofilms. To identify which surface parameters provide guidance for the development of novel stent materials, we used an in vitro encrustation system. Synthetic urine with increasing pH to simulate an infection situation was pumped over the polymer samples with adjusted flow rates at 37 °C to mimic the native body urine flow. Chemical surface features (contact angle, surface charge), as well as encrustations were characterized. The encrustations on the materials were analyzed quantitatively (dry mass) and qualitatively using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and Fourier transform infrared spectroscopy (FTIR). The aim of this comparative study was to identify crucial surface parameters that might predict the quantity and type of mineral deposits in vitro and provide guidance for the development and screening of new polymer-based biomaterials for ureteral stent design. For the first time, we could identify that, within the range of our polymers, those materials with a slight hydrophilicity and a strong negative zeta potential (around −60 mV) were most favorable for use as ureteral stent materials, as the deposition of crystalline biofilms was minimized.

Individualized patient care with urological implants using biofilm-resistant surface concepts

Urological implants in the urinary tract are routinely used to ensure urine flow. However, the morbidities are numerous concerning long-term derivations. Especially with the ureteral stents, failure can have considerable consequences. Since the surfaces of all urological implants are more or less ideal substrates for microorganisms, the formation of bacterial biofilms is aregularly observed and often serious complication, which in many cases forces early implant replacement. The burden on the patient and the health system are enormous. This article provides an overview of the numerous strategies developed or under development to protect against bacterial adhesion. Observations in use show "sometimes good, sometimes bad results" for all strategies, which may be due to the fact that the treated patients have different biological and clinical conditions. The implants are each equipped with defense mechanisms designed for certain "scenarios"; if they are used inadequately in this respect, they cannot optimally fulfill their task. Systematic observations of the "outcomes" and evaluation of the obtained data would be necessary in order to be able to assign an "optimal" effect spectrum to each defense strategy, thus, ultimately prospectively giving patients the most suitable product in advance. Systematic use of the existing implant concepts can avoid alarge number of implant-related complications "ad hoc"; further development steps with regard to improved surface modifications can be made more specifically. However, the hope of a"super strategy" is likely to remain unfulfilled because bacteria as "opponents" have already proved billions of years of survival.

Hydrogenated amorphous carbon coatings on implants drastically reduce biofilm formation and water permeation

Inflammations and crystalline bacterial biofilms (encrustations) remain a major complication in long-term artificial urinary tract drainage. To solve this problem we present urological implants with coatings made of amorphous hydrogenated carbon (a-C:H) that show excellent protection from encrustation in-vitro as well as in-vivo. Part of the success of a-C:H coatings is attributed to their ability to act as a diffusion barrier between an implant and the body, which prevents leaching of solvents from polymeric implants. To further enhance their barrier properties a-C:H coatings are combined with parylene coatings to develop diffusion-barrier multilayer coatings with a total thickness between 0.2 μm and 0.8 μm. The combination of the two types of coatings leads to a reduction of water diffusion by a factor of up to ten with respect to uncoated 25 μm thick polyimide sub-strates. The diffusion of water vapour from a controlled atmospheric pressure chamber through coated foils to a vacuum chamber is measured in a custom-built device.

Failure of Urological Implants in Spinal Cord Injury Patients due to Infection, Malfunction, and Implants Becoming Obsolete due to Medical Progress and Age-Related Changes in Human Body Making Implant Futile: Report of Three Cases

Any new clinical data, whether positive or negative, generated about a medical device should be published because health professionals should know which devices do not work, as well as those which do. We report three spinal cord injury patients in whom urological implants failed to work. In the first, paraplegic, patient, a sacral anterior root stimulator failed to produce erection, and a drug delivery system for intracavernosal administration of vasoactive drugs was therefore implanted; however, this implant never functioned (and, furthermore, such penile drug delivery systems to produce erection had effectively become obsolete following the advent of phosphodiesterase type 5 inhibitors). Subsequently, the sacral anterior root stimulator developed a malfunction and the patient therefore learned to perform self-catheterisation. In the second patient, also paraplegic, an artificial urinary sphincter was implanted but the patient developed a postoperative sacral pressure sore. Eight months later, a suprapubic cystostomy was performed as urethral catheterisation was very difficult. The pressure sore had not healed completely even after five years. In the third case, a sacral anterior root stimulator was implanted in a tetraplegic patient in whom, after five years, a penile sheath could not be fitted because of penile retraction. This patient was therefore established on urethral catheter drainage. Later, infection with Staphylococcus aureus around the receiver block necessitated its removal. In conclusion, spinal cord injury patients are at risk of developing pressure sores, wound infections, malfunction of implants, and the inability to use implants because of age-related changes, as well as running the risk of their implants becoming obsolete due to advances in medicine. Some surgical procedures such as dorsal rhizotomy are irreversible. Alternative treatments such as intermittent catheterisations may be less damaging than bladder stimulator in the long term.

Does heparin coating reduce encrustation of biliary plastic endoprostheses? A prospective randomized trial

Objective. Common bile duct stenting is widely performed for bridging benign and malignant obstructions. A major limitation is early stent occlusion making regular stent exchange necessary. Covalent binding of glycosaminoglycanes to polyethylene stents proved to reduce encrustation in urological implants. Since development of urological and biliary stent occlusion shows parallels, the aim of the study was to evaluate the efficacy of heparin coating of biliary endoprostheses in preventing encrustation. Material and methods. In a prospective randomized trial, heparin-coated and native stents were endoscopically placed for almost 90 days on average. After removal, all stents were dried (50°C, 24 h), weighed and after longitudinal incision visible encrustation and discoloration recorded. Fifty-three patients (21 females/32 males, 70 ± 12 (42–87) years) were included; 13 patients (4 females/9 males, 58–79 years) completed the study according to the protocol. Results. After removal, mean weight of encrustation in native stents was more than double as high as of covered stents (native: 37.9 ± 19.8 (16–93) mg; covered: 17.6 ± 6.7 (9–33) mg). In 12 of 13 cases, the encrustation weight of the native stent was higher than that of the corresponding covered stent in the same patient. Premature stent explantation became necessary in 3 of 13 native stents, because of recurrent jaundice or cholangitis but only in 1 of 13 covered stents. After longitudinal incision, the three uncovered stents showed excessive encrustation whereas no significant encrustation was found in the covered prosthesis. Altogether, covered stents showed less visible accumulation of clogging material and discoloration than native stents. Conclusions. Covalent bound heparin is highly effective in preventing encrustation of biliary polyethylene endoprostheses.

Characteristics of bacterial biofilm associated with implant material in clinical practice

Colonization of bacteria around native host cells or polymeric implant surfaces results in a dense growth on the surface, which leads to infection. The change of a bacterium from a motile planktonic to a nonmotile long chain of growing cells is a complex, regulated process that depends on several factors. The probability of a biofilm-related infection occurrence is between 65 and 80%. This review critically evaluates the mode of biofilm formation on native tissues and orthopedics, dental, cardiac, and urological implants and vascular grafts. The combination of biochemical advancements with conventional microbiological techniques and the use of radio-labeled monoclonal antibodies in imaging techniques, with recent developments in the detection of these biofilm in vivo, would help in designing biomaterials that prevent bacterial adhesion and biofilm formation, and dislodge the formed biofilm, thereby accelerating the product development phase. With the increase in the number of implant-dependent surgeries and biofilm-associated complications, there is a need to counteract and deal with this phenomenon. This has led to various approaches to elucidate the etiology and pathogenesis of the infection. This review critically evaluates the formation, characteristics, pathogenicity and the molecular genetics of both implant- and nonimplant-associated medical biofilm.

Uropathogen Interaction With the Surface of Urological Stents Using Different Surface Properties

Ureteral stents commonly become infected or encrusted. Various coatings have been developed to decrease bacterial adherence. To our knowledge there has been no in vitro testing of coating with heparin to date. We determined the effects of heparin coating on bacterial adherence of common uropathogens and physical stent properties. Heparin coated Radiance ureteral stents (Cook) and noncoated Endo-Sof control stents were tested against triclosan eluting Triumph(R) stents and noneluting Polaris control stents for adherence of Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Staphylococcus aureus and Pseudomonas aeruginosa for 7 days. Adherent bacteria were determined and biofilms were visualized using fluorescent dyes. Radial, tensile and coil strength of the Radiance and Polaris stents was compared to determine the effect of heparin coating on physical stent characteristics. Heparin coating did not decrease bacterial adhesion compared to its control. E. coli adhesion was limited by all stents tested. The Polaris stent showed significantly greater resistance to bacterial adherence for Klebsiella, Pseudomonas and Enterococcus than the Endo-Sof and Radiance stents but was more susceptible to S. aureus adherence. The Triumph stent resisted all bacteria except Pseudomonas and Enterococcus. Mature biofilms were observed on all stents with lower viability on the Triumph stent. Radiance stents showed higher tensile and lower compression strength than its control. Heparin coating does not decrease bacterial adherence to ureteral stents. Drug eluting antimicrobials have an inhibitory effect on bacterial adherence and the Polaris stent showed the least bacterial adherence of the nondrug eluting ureteral stents tested.

Reduction of Biofilm Formation on a‐C:H Coated Implants: Investigation of Biofilm‐Surface Interactions by Variation of Thin Film Properties

AbstractFormation of crystalline bacterial biofilms (encrustations) on urological implants remains a major complication in patient care. Recently, it was shown that amorphous carbon (a‐C:H) coatings deposited on polyurethane (PU) stents provide a distinct reduction in biofilm formation with an effect more pronounced in‐vivo than in‐vitro. To investigate the underlying mechanisms, the influence of surface properties on the encrustation tendency of plasma coated and uncoated PU tubes was tested in an extended in‐vitro model with protein‐spiked artificial urine and urease. In the presence of albumin the formation of hollow crystalline spheres was observed mainly on uncoated PU. We suggest that evolving gas bubbles influence protein adherence and attachment of crystalline bacterial biofilm to the implant surfaces.

Antiinfective and encrustation-inhibiting materials—myth and facts

Catheters, urethral and ureteral stents and other urological implants are frequently affected by encrustration and infection due to their permanent contact with urine. Indwelling urinary catheters provide a haven for microorganisms and thus require extensive monitoring. Several surface modification techniques have been proposed to improve the performance of devices including the immobilization of biomolecules, the incorporation of hydrophilic grafts to reduce protein adsorption, the creation of hydrophobic surfaces, the creation of microdomains to regulate cellular and protein adhesion, new polymers and antimicrobial coatings. Physico-chemical explanation to elucidate the mechanism of such encrustation or infection inhibiting materials is still not available. Our series of experiments showed a marked decrease of silver-activity in biological fluids which corresponds with the controversial clinical results obtained with silver coated urinary catheters. Rifampicin/minocycline coated catheters had very low activity against Gram-negative rods, enterococci and Candida spp., the main causing organisms of urinary catheter infection. Surface engineered materials and antimicrobial drug delivery systems will be the next generation of sophisticated urinary catheters and stents, if both efficacy as well as efficiency has been proved clinically.

Prevention of surface encrustation of urological implants by coating with inhibitors

The encrustation of materials used for urological implants is as yet an unresolved problem. The crystallisation-inhibiting effect of the glycosaminoglycan heparin was used to reduce encrustation. Heparin was covalently bound to the surface of slotted-tube stents of tantalum and stainless steel using a spacer molecule. To verify the inhibition of crystallisation processes, reproducible in vitro tests and in vivo tests using the rat as animal model were carried out. The in vitro and in vivo experiments showed that the heparin coating has a significant influence on the encrustation of the surface. After 7 days in vitro and 120 days in vivo, heparin coated stents were free of encrustation, whereas the uncoated reference stents were extensively covered.