History of peritoneal access development

The first peritoneal accesses were devices that had been used in other fields (general surgery, urology, or gynecology): trocars, rubber catheters, and sump drains. In the period after World War II, numerous papers were published with various modifications of peritoneal dialysis. The majority of cases were treated with the continuous flow technique; rubber catheters for inflow and sump drains for outflow were commonly used. At the end of the 1940s, intermittent peritoneal dialysis started to be more frequently used. Severe complications of peritoneal accesses created incentive to design accesses specifically for peritoneal dialysis. The initial three, in the late 1940s, were modified sump drains; however, Ferris and Odel for the first time designed a soft, polyvinyl intraperitoneal tube with metal weights to keep the catheter tip in the pelvic gutter where the conditions for drain are the best. In the 1950s, intermittent peritoneal dialysis was established as the preferred technique; polyethylene and nylon catheters became commercially available and peritoneal dialysis was established as a valuable method for treatment of acute renal failure. The major breakthrough came in the 1960s. First of all, it was discovered that the silicone rubber was less irritating to the peritoneal membrane than other plastics. Then, it was found that polyester velour allowed an excellent tissue ingrowth creating a firm bond with the tissue. When a polyester cuff was glued to the catheter, it restricted catheter movement and created a closed tunnel between the integument and the peritoneal cavity. In 1968, Tenckhoff and Schechter combined these two features and designed a silicone rubber catheter with a polyester cuff for treatment of acute renal failure and two cuffs for treatment of chronic renal failure. This was the most important development in peritoneal access. Technological evolution never ends. Multiple attempts have been made to eliminate remaining complications of the Tenckhoff catheter such as exit/tunnel infection, external cuff extrusion, migration leading to obstruction, dialysate leaks, recurrent peritonitis, and infusion or pressure pain. New designs combined the best features of the previous ones or incorporated new elements. Not all attempts have been successful, but many have. To prevent catheter migration, Di Paolo and his colleagues applied the old idea of providing weights at the catheter tips to Tenckhoff catheters. In another modification, Twardowski and his collaborators created a permanent bend to the intra-tunnel portion of the silicone catheter to eliminate cuff extrusions. The Tenckhoff catheter continues to be widely used for chronic peritoneal dialysis, although its use is decreasing in favor of swan-neck catheters. Soft, silicone rubber instead of rigid tubing virtually eliminated such early complications as bowel perforation or massive bleeding. Other complications, such as obstruction, pericatheter leaks, and superficial cuff extrusions have been markedly reduced in recent years, particularly with the use of swan-neck catheters and insertion through the rectus muscle instead of the midline. However, these complications still occur, so new designs are being tried.     

Biocompatibility of platinum-metallized silicone rubber: in vivo and in vitro evaluation

Silicone rubber is commonly used for biomedical applications, including implanted cuff electrodes for both recording and stimulation of peripheral nerves. This study was undertaken to evaluate the consequences of a new platinum metallization method on the biocompatibility of silicone rubber cuff electrodes. This method was introduced in order to allow the manufacture of spiral nerve cuff electrodes with a large number of contacts. The metallization process, implying silicone coating with poly(methyl methacrylate) (PMMA), its activation by an excimer laser and subsequent electroless metal deposition, led to a new surface microtexture. The neutral red cytotoxicity assay procedure was first applied in vitro on BALB/c 3T3 fibroblasts in order to analyze the cellular response elicited by the studied material. An in vivo assay was then performed to investigate the tissue reaction after chronic subcutaneous implantation of the metallized material. Results demonstrate that silicone rubber biocompatibility is not altered by the new platinum metallization method.     

Biocompatibility of platinum-metallized silicone rubber: in vivo and in vitro evaluation

Silicone rubber is commonly used for biomedical applications, including implanted cuff electrodes for both recording and stimulation of peripheral nerves. This study was undertaken to evaluate the consequences of a new platinum metallization method on the biocompatibility of silicone rubber cuff electrodes. This method was introduced in order to allow the manufacture of spiral nerve cuff electrodes with a large number of contacts. The metallization process, implying silicone coating with poly(methyl methacrylate) (PMMA), its activation by an excimer laser and subsequent electroless metal deposition, led to a new surface microtexture. The neutral red cytotoxicity assay procedure was first applied in vitro on BALB/c 3T3 fibroblasts in order to analyze the cellular response elicited by the studied material. An in vivo assay was then performed to investigate the tissue reaction after chronic subcutaneous implantation of the metallized material. Results demonstrate that silicone rubber biocompatibility is not altered by the new platinum metallization method.     

A family of neuromuscular stimulators with optical transcutaneous control

A family of miniature implantable neuromuscular stimulators has been developed using surface-mounted Philips 4000-series integrated circuits. The electronic components are mounted by hand on printed circuits (platinum/gold on alumina) and the electrical connections are made by reflow soldering. The plastic integrated-circuit packages, ceramic resistors and metal interconnections are protected from the body fluids by a coating of biocompatible silicone rubber. This simple technology provides reliable function for at least 4 months under implanted conditions. The circuits have in common a single lithium cell power-supply (3.2 V) and an optical sensor which can be used to detect light flashes through the skin after the device has been implanted. This information channel may be used to switch the output of a device on or off, or to cycle through a series of pre-set programs. The devices are currently finding application in studies which provide an experimental basis for the clinical exploitation of electrically stimulated skeletal muscle in cardiac assistance, sphincter reconstruction or functional electrical stimulation of paralysed limbs.     

Improving the efficiency of a tubular membrane oxygenator.

The development of a tubular membrane oxygenator is described. Fine silicone rubber tubes are inserted into a large silicone rubber tube and sealed. Oxygen is blown through the fine tubes, blood flows through the large tube, and the gases are exchanged through the wall of the fine tubes. The efficiency of the device is improved by increasing the gas pressure, which is followed by bubble formation in the blood, and which is therefore unacceptable. By arranging the inside tubes in a wavy pattern and by repeatedly stretching them the efficiency is increased without side effects.     

Bacterial adhesion and growth on a polymer brush-coating

Biomaterials-related infections pose serious problems in implant surgery, despite the development of non-adhesive coatings. Non-adhesive coatings, like polymer brush-coatings, have so far only been investigated with respect to preventing initial bacterial adhesion, but never with respect to effects on kinetics of bacterial growth. Here, we compare adhesion and 20h growth of three bacterial strains (Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa) on pristine and brush-coated silicone rubber in a parallel plate flow chamber. Brush-coatings were made using a tri-block copolymer of polyethylene oxide (PEO) and polypropylene oxide (PPO). Brush-coatings prevented adhesion of staphylococci to below 5x10(5)cm(-2) after 30min, which is a 10-fold reduction compared to pristine silicone rubber. Biofilms grew on both brush-coated and pristine silicone rubber, while the viability of biofilms on brush-coatings was higher than on pristine silicone rubber. However, biofilms on brush-coatings developed more slowly and detached almost fully by high fluid shear. Brush-coating remained non-adhesive after S. epidermidis biofilm formation and subsequent removal whereas a part of its functionality was lost after removal of S. aureus biofilms. Adhesion, growth and detachment of P. aeruginosa were not significantly different on brush-coatings as compared with pristine silicone rubber, although here too the viability of biofilms on brush-coatings was higher. We conclude that polymer brush-coatings strongly reduce initial adhesion of staphylococci and delay their biofilm growth. In addition, biofilms on brush-coatings are more viable and easily removed by the application of fluid shear.     

Solubility and diffusion coefficients of gaseous formaldehyde in polymers

The solubility and diffusion (desorption) coefficients of gaseous formaldehyde in 14 materials have been measured at different temperatures. Cellulose, paper, polyamide (Nylon 6), polyester and natural rubber (latex) show very high values of formaldehyde solubility and very low diffusion coefficients, with a weak or inversed influence of the temperature, leading to the conclusion that a chemical reaction occurs with the formaldehyde. The behaviour of the other polymers follows the classical laws of solubility and diffusion of gases except for silicone rubber which shows two-phase desorption curves.     

Antimicrobial activity of silicone rubber used in hydrocephalus shunts, after impregnation with antimicrobial substances.

Colonisation of cerebrospinal fluid shunts by coagulate-negative staphylococci (Staphylococcus albus) is a serious problem. Because of its possible role in prevention of the condition, the antimicrobial activity of silicone rubber after impregnation with antimicrobial drugs was studied. The method of impregnation used and test methods were found to be important. Formaldehyde-urea condensates gave no activity. Gentamicin sulphate gave activity which was short-lived. Sodium and diethanolamine fusidates and clindamycin hydrochloride gave prolonged activity. A method of impregnation was developed which could be applied to commercially available shunts before use.     

Reaction associated with a silicone rubber gel: an experimental study.

A blend of Silastic 382 (Room Temperature Vulcanizing, RTV) Medical Grade silicone oil and a catalyst was prepared in vitro, in both the catalyzed and noncatalyzed state, and injected subcutaneously in mice, rats, and rabbits. When properly blended, this catalyzed material, referred to as "silicone gel," formed a soft rubbery mass that remained at the site of injection. Properly catalyzed silicone rubber gel produces no macroscopic inflammatory reaction, attracts few polymorphonuclear leucocytes, and after 5-6 days a thin fibrous capsule begins to form aroung the gel. No degeneration of the silicone gel was observed during the 62 days of this experiment. Additional rats with this silicone gel have been under observation for 8 months and clinically have shown no changes in the local mass of silicone. If the catalyst is partly oxidized when added to the silicone fluid, the degree of gelling is much less. A local mass usually forms at the site of injection with some of the fluid diffusing into the tissue, forming minute cysts. The inflammatory reaciton is characterized by polymorphonuclear leucocytes, associated with many macrophages and giant cells phagocytizing oil droplets and particles of the diatomaceous earth. The pathogenesis of the inflammatory reaction is discussed, referring to the ionic change and the emigration of polymorphonuclear leucocytes to particles of plastics embedded in tissue.     

PRES: The Controlled Noninvasiv Stimulation of the Carotid Baroreceptors in Humans

To study physiological and psychological effects of baroreceptor activity, the cervical neck cuff technique has been frequently used to stimulate the carotid baroreceptors mechanically. Using this technique, no satisfying control conditions to date have been available. Because the carotid stretch receptors are sensitive not only to the pressure level, but also to the rate of change, it is possible to manipulate the receptor firing through changes in carotid pulse amplitude. The device described here relies on the application of short changes in cuff pressure tied to different phases within the cardiac cycle (phase related external suction (PRES)). A brief external suction during systole has potent stimulatory effects on baroreceptors whereas the application of the very same pressure pulse during diastole inhibits the firing burst associated with the pulse wave. To allow an ongoing period of stimulation, a sequence of alternating negative/positive pressure pulses is applied. In the stimulation condition, the R-wave of the electrocardiogram triggers a negative pulse which is followed by a positive one during diastole. In the control condition this relationship is reversed. Two experiments are reported confirming different baroreceptor effects of the two conditions. PRES allows for blind or double-blind experiments to investigate effects of baroreceptor activity on physiology and behavior.     

Comparison of corneal epithelial cellular growth on synthetic cornea materials.

The application of artificial corneas for severely wounded ocular surfaces has always encountered the problem of biocompatibility with corneal epithelial cells (CECs). For the eye to stay healthy, it must continually have a complete sheet of CECs across the artificial corneal surface. Various surface modifications of different polymeric materials have been examined to determine which have the best cellular growth rates. A mathematical model of corneal cell growth profiles on synthetic materials was formulated based upon a linear mitotic growth rate. Experimental data reported for the CEC growth on modified poly(vinyl alcohol), silicone rubber, polystyrene, and polycarbonate was analyzed using the model to estimate the linear mitotic rate constant (k). The model proved to be useful in comparing data from different investigators. Plasma-induced graft copolymerized poly(hydroxyethyl methacrylate) (pHEMA) on silicone rubber provided the best growth rate from this particular set of data.     

Implantable microelectrodes with new electro-conductive materials for recording sympathetic neural discharge

We have developed two new types of bipolar cuff microelectrodes (volume size, 2-3 mm(3)) using electro-conductive rubber or water-absorbent polymer, either of which can be applied to measure sympathetic nerve activity in small animals. A renal nerve bundle of an anesthetized rat was inserted into the center hole of the electrode (diameter, 0.15 mm) through a slit and had good contact with the electrodes. Renal sympathetic nerve activity, which was verified by sympathetic ganglionic blockade, could be recorded using either type of implantable cuff electrode.     

Surface modification of an experimental silicone rubber aimed at reducing initial candidal adhesion

Silicone rubber, which is a widely used biomaterial, is often used to make soft liners for permanent denture. Colonization of denture soft lining materials by Candida albicans can result in clinical problems. The aim of this study was to chemically modify the surface of an experimental silicone rubber in order to produce a silicone that was less susceptible to candidal colonization. Surface modification was carried out with the use of argon-plasma bombardment followed by silane treatment, which caused the incorporation of either hydrophilic or hydrophobic functional groups onto the surface. Changes in water contact angles and chemical analysis of the materials with scanning ion mass spectroscopy confirmed surface changes. In vitro assays were carried out using C. albicans to measure levels of adherence to the surface-modified silicone after 1 h. C. albicans exhibited very low adherence to all silane-treated surfaces, whether hydrophobic or hydrophilic. This led to the conclusion that incorporated long-chain functional groups were inhibiting the adherence of the yeast, possibly by the formation of a barrier between the surface of the material and the yeast. In conclusion, silane surface treatment of an experimental silicone rubber has been successful in reducing candidal adherence.     

Radiotelemetry of avian electrocardiogram

A radiotelemetry system has been developed which is capable of transmitting electrocardiogram signals from domestic fowl. The transmitter circuit consists of a frequency-modulated Colpitts oscillator operating at 104·5 MHz, followed by a single-ended amplifier. The devices are fabricated as thin-film hybrid microcircuits. Transmitters were encapsulated in silicone rubber and implanted subcutaneously over the pectoral muscles in domestic fowl. Several sites for electrode placement were tried. The most successful yielded a large distinct QRS complex, which could be used as a trigger in measuring heart rate, and a good ratio of usable to unusable trace. These results were obtained when the electrodes were sutured 60 mm apart to the connective tissue covering the keel bone. Implantation of the devices did not affect the behaviour of the birds and there were no pathological lesions associated with them up to four weeks later.     

Mechanical properties of antibacterial silicone rubber for hydrocephalus shunts.

In an effort to find a solution to the serious problem of bacterial colonization of cerebrospinal-fluid shunting devices, room-temperature and heat-vulcanizing silicone rubbers were impregnated with gentamicin sulphate. The effects on the mechanical properties of the two rubbers were studied. Results show that the tensile strength and extensibility of the room-temperature-vulcanizing silicone rubber reduced with increasing concentration of the drug. For the heat-vulcanizing silicone rubber, the tensile strength was also found to decrease with increasing drug content. The extensibility after an initial reduction at low concentrations was found to increase at drug concentrations in excess of 10 mg/g. Nevertheless, the changes in mechanical properties measured are considered not to be so great as to preclude the application of drug-impregnated silicone rubbers to cerebrospinal-fluid shunting devices.     

Thrombus formation in a staged capillary membrane oxygenator associated with a microaggregate blood filter: a scanning electron microscope study

Blood contact at interfaces in extracorporeal devices is a source of traumas. Proteins are very rapidly adsorbed; then, depending on which proteins are left various degrees of platelet aggregation follow and thrombi develop. The scanning electron microscope reveals very instructive information on the morphology of the blood deposits which adhere to foreign surfaces. Oxygenators such as the Awad D, which is a staged one made of silicone rubber, become "thrombus invaded" after prolonged extracorporeal circulation in spite of adequate heparinization of the blood. In most cases, evaluation of membranes and devices is assessed with respect to transfer of blood gases. Careful examination of the morphology of deposits should be developed. This study shows the importance of blood flow rate, design, and materials.     

A simple electrode for intact nerve stimulation and/or recording in semi-chronic rats

A cuff electrode for extracellular nerve stimulation and/or recording is described. It can be made from common laboratory material without the need of special equipment, and consists of a tubular silicone rubber holder enclosing the nerve and keeping it in position against two platinum wires. The assembly is sufficiently insulated to be kept amidst the surrounding tissue, hereby preventing the nerve to dry during recording periods. It can be attached to an adjoining structure, thus allowing further manipulation of the animal.     

Problems of encapsulation of total joint replacements

Particulate wear debris of artificial joints, metallic and plastic, and solutions of metals in body fluids are known to have adverse effects. Encapsulation of the articulating parts would prevent wear debris from entering the surrounding tissue and check tissue ingrowth into the joint. The capsule could contain an artificial lubricant to reduce friction and wear and increase the joint life.For the capsule material, several bioelastomers are being tested in an environment of body fluids and lubricants. Three fatigue rigs have been developed for these tests. Tests have shown that a bovine synovial fluid environment causes a tenfold increase in the fatigue life of silicone rubber. A special capsule shape for minimizing stresses due to creasing is being investigated.Electrophoresis has been explored as a method of filtration of wear debris. It has been shown that Co-Cr-Mo alloy wear particles are attracted to polymers having a permanent negative surface charge.     

Curing behavior of silicone elastomer in the presence of two corticosteroid drugs

Silicone rubbers are widely used as carriers for delivery of drugs intended for parenteral administration as implantable devices. Drugs having different functional groups can significantly affect curing profile of silicone rubber, which in turn may negatively affect their biological applicability due to the loss in mechanical and drug retaining properties. To this end, the effects of two corticosteroid analogs (up to 2 %w/w of drug loading) that is, dexamethasone (DEX) and its sodium phosphate ester (DSP) on curing behavior of a non-restricted, two part RTV silicone rubber was studied using different characterization techniques including spectroscopic (FTIR), calorimetric (DSC), oscillating disk rheometry, and swelling studies. The results showed that curing time extends longer for DSP-loaded samples compared to the non-loaded silicone rubber. The presence of DSP in the formulation interferes in the curing of silicone elastomers, probably due to the thermal decomposition of DSP according to the spectral changes observed in FTIR spectra as confirmed by DSC analysis. Rheometric studies showed depreciated properties for silicone elastomers upon compounding with DSP. Swelling measurements indicated to lowered crosslink density for networks and increasing M(c) upon adding DSP to the formulations which can be attributed to disruption in crosslinking reaction by sodium phosphate moieties of DSP.     

Impregnation of soft biological specimens with thermosetting resins and elastomers

A new method for impregnation of biological specimens with thermosetting resins and elastomers is described. The method has the advantage that the original relief of the surface is retained. The impregnation is carried out by utilizing the difference between the high vapor tension of the intermedium (e.g., methylene chloride) and the low vapor tension of the solution to be polymerized. After impregnation, the specimen is subject to polymerization conditions without surrounding embedding material. The optical and mechanical properties can be selected by proper choice from various kinds of resins and different procedures, for example, by complete or incomplete impregnation. Acrylic resins, polyester resins, epoxy resins, poly-urethanes and silicone rubber have been found suitable for the method. Excellent results have been obtained using transparent silicone rubber since after treatment the specimens are still flexible and resilient, and have retained their natural appearance.