Biocompatibility Performance Research Articles

The application of animal models to study the biocompatibility of bicarbonate-buffered peritoneal dialysis solutions

The application of animal models to study the biocompatibility of bicarbonate-buffered peritoneal dialysis solutions. Patients treated with peritoneal dialysis (PD) are at risk for development of ultrafiltration failure and peritonitis. These two significant complications can result in the termination of PD treatment. The relative unphysiologic composition of the currently used standard peritoneal dialysis fluids (PDF) is considered to be a major cause for the development of morphologic changes of the peritoneal membrane, ultimately resulting in ultrafiltration failure and probably contributing to changes in local defense mechanisms with the associated increased risk of peritonitis. In recent years, a major research focus has become the development of new and improved PD solutions. This has resulted in the development of an amino-acid-based PDF, a glucose polymer-based PDF, and several bicarbonate-buffered PDF. Typically, the first phase of biocompatibility testing of new PD solutions involves in vitro testing, employing isolated cells such as peritoneal macrophages or cell culture systems using human peritoneal mesothelial cells. The results of such evaluations are useful in providing insights into the biocompatibility performance of any given formulation, but suffer from several disadvantages, which can be better addressed using animal models. In vivo studies using animals permit the analysis of biocompatibility under conditions that allow for cell-to-cell interactions and dynamic changes in solution composition that more closely mimic the clinical situation. In this paper, we will review the use of animal models for the study of PDF biocompatibility and their application to the assessment of bicarbonate-buffered PDF.

In vitro biocompatibility performance of Physioneal

In vitro biocompatibility performance of Physioneal. toneal dialysis (PD) has been a successful and effective form of chronic renal replacement therapy since its introduction over 20 years ago. Despite its overall success, there is a growing body of evidence that suggests shortcomings in the preservation of membrane integrity. This has led to the development of several second-generation PD solutions that demonstrate improved biocompatibility. Physioneal, a neutral pH, bicarbonate/lactate-buffered solution, was one of the first of these new PD solutions to become commercially available. This review will focus on one of the first preclinical stages in the development of Physioneal: studies on in vitro biocompatibility testing. Studies in leukocyte, mesothelial cell, and fibroblast populations demonstrated significantly improved biocompatibility of neutral pH, bicarbonate/lactate-based solutions compared to conventional solutions. The solutions contributed to improved leukocyte viability and response to bacterial infection (e.g., phagocytosis, superoxide radical generation, and endotoxin-stimulated cytokine release). Studies on peritoneal mesothelial cells demonstrate improved cell viability, proliferation, and response to proinflammatory stimuli, and a reduced potential for angiogenesis and peritoneal fibrosis, all suggesting a better preservation of membrane structure and function. The bicarbonate/lactate-based solutions demonstrated decreased cytotoxicity and preserved cell growth in fibroblast cultures as well. In vitro biocompatibility testing has clearly demonstrated that neutral pH, bicarbonate/lactate-buffered Physioneal solutions are superior to conventional solutions in preserving cell viability and function in cell populations that contribute to peritoneal homeostasis. This positive assessment now provides a foundation and rationale for moving forward with the next stages in preclinical testing: in vivo animal models and human ex vivo studies.

Hemolytic characteristics of oxygenators during clinical extracorporeal membrane oxygenation.

A connection was previously reported between the hemolytic characteristics associated with oxygenators and the pressure drop measurements in the blood chamber under experimental conditions simulating their use in cardiopulmonary bypass. We examined this association during extracorporeal membrane oxygenation (ECMO) conditions. Three oxygenators for ECMO or pediatric cardiopulmonary bypass (Menox EL4000, Dideco Module 4000, and Mera HPO-15H) were evaluated. Fresh blood from healthy Dexter strain calves anticoagulated with citrate phosphate dextrose adenine solution was used. The blood flow was fixed at 1 L/min, similar to that in ECMO. The Normalized Index of Hemolysis for Oxygenators (NIHO) has been modified according to the American Society of Testing and Materials standards, as was previously reported. The NIHO value was the lowest in the Menox (0.0070+/-0.0009) and increased from Menox to Dideco (0.0113+/-0.0099) to Mera (0.0164+/-0.0043); however, there were no significant differences among the oxygenators. This NIHO value has a close correlation to the pressure drop. In conclusion, this evaluation method is also applicable to comparison of the biocompatibility performance of different types of clinically available oxygenators for ECMO.

HEMOLYTIC CHARACTERISTICS OF CLINICALLY ACCEPTED OXYGENATORS DURING ECMO

Specific aim; A connection was previously reported between the hemolytic characteristics associated with oxygenators and the pressure drop measurements in the blood chamber under experimental conditions simulating their use in cardiopulmonary bypass (CPB). At this time, we examined this association during extracorporeal membrane oxygenation (ECMO) condition. Method; Three oxygenators for ECMO or pediatric CPB (Menox EL4000®, Dideco Module 4000®, and Mera HPO-15H®) were evaluated. Fresh blood from healthy Dexter strain calves anti-coagulated with citrate phosphate dextrose adenine solution was used. The blood flow was fixed at 1 L/min similar to ECMO. The Normalized Index of Hemolysis for Oxygenators (NIHO) has been modified according to the American Society of Testing and Materials (ASTM) standards as we previously reported. Result; The NIHO value was the lowest in the Menox (0.0070 ± 0.0009) and increased from Menox <Dideco (0.0113 ± 0.0099) <Mera (0.0164 ± 0.0043); however, there were no significant differences among the oxygenators. This NIHO value has a close correlation to the pressure drop. Conclusion; This evaluation method is also applicable to compare the biocompatibility performance of different types of clinically available oxygenators for ECMO usage.

BLOOD TRAUMA INDUCED BY CLINICALLY ACCEPTED OXYGENATORS

Specific aim; Hemolysis remains one of the most serious problems during ECMO and PCPS. However, the hemolytic characteristics associated with oxygenators are not well defined. A specialized hemolysis test protocol for oxygenators was developed. A comparative study was performed following this protocol to determine the hemolytic characteristics of the clinically available oxygenators. Method; Three oxygenators (Avecor 1500®, Optima®, Menox EL 4000®) were evaluated. The blood flow was fixed at 1 or 5 L/min as an ECMO or cardiopulmonary bypass, respectively. The Normalized Index of Hemolysis for Oxygenator (NIHO) has been modified according to the American Society of Testing and Materials (ASTM) standards. The NIHO value, which was obtained from the circuit without an oxygenator was subtracted from the primary NIHO value, which was obtained from the circuit with an oxygenator to eliminate the effects of a centrifugal pump or other artifacts. Result; NIHO of each oxygenator is as follows. (g/100L)TableConclusion; This new evaluation method is suitable to compare the biocompatibility performance of different types of clinically available oxygenators.

Process for the manufacture of a type reinforcement: Debroche C. and Laurent D. (Compagnie General des Etablissements Michelin, Clermont-Ferrand, France) US Pat 4 952 259 (28 August 1990)

The development of orthopedic implant materials which promote osseointegration and reduce bacterial infection has gained considerable attention to avoid long-term complications in the biomedical industry. Present study reports the electrodeposition of strontium-halloysite nanotubes (Sr-Hal)/lanthanum, cerium substituted hydroxyapatite (La,Ce-HAP) composite coatings on titanium surface with varying Sr-Hal concentration at 1, 2 and 3 wt%. Their physicochemical and morphological characterizations were performed. The mechanical properties of the coatings were evaluated using adhesion and microhardness tests and from the obtained results it was found that, the incorporation of Sr-Hal improved the mechanical properties of the composite coatings. The electrochemical assessment of composite coated Ti surfaces in simulated body fluid (SBF) solution was investigated using polarization measurements. The anti-corrosion properties of the Sr-Hal/La,Ce-HAP composite coated Ti with 3 wt% Sr-Hal was found to be excellent compared to the other wt% of Sr-Hal incorporated in the composite. The antibacterial, anti-cancer and cell viability study of Sr-Hal/La,Ce-HAP composite coatings and their results reveal the bactericidal effect, osteosarcoma cell growth impediment and higher number of viable cells respectively. As a whole, all the studies exposed that the Sr-Hal/La,Ce-HAP composite coatings on Ti has improved the mechanical, anticorrosion and biocompatible performance indicating the Sr-Hal/La,Ce-HAP composite coated titanium is a prospective implant material for orthopedic applications.

The effect of the physiological environment on the mechanical properties of biomaterials in cardiovascular applications.

The long-term biocompatibility and physical performance of polymeric materials in the physiological environment depend both on adsorption and absorption processes. While the former has received significant attention in the literature, the latter has not been sufficiently appreciated. Accelerated testing of prosthetic devices in the wrong media and temperatures yield misleading information as exemplified by pumping bladders of heart assist devices and heart valves. Although glutaraldehyde-treated porcine heterograft heart valves performed better than expected in humans over a period of several years, physical degradations that have been observed may be associated with the breakdown of the cross-links. Appropriately selected smooth-surfaced biomaterials and hydrogels are far better suited for temporary blood contacting prosthetic applications such as left ventricular heart assist devices (LVADs) than polyester flocked fibril surfaces that result in the deposition of a thick layer of fibrin/cellular mesh with clot-like morphology with inherent dangers of loss of polyester fibrils, and the shedding of clots as the result of cyclic flexing of the pump bladders. With the proliferation of various medical devices, the possibility of increased litigations with secondary and tertiary liabilities involving not only physicians, surgeons, and device manufacturers, but also suppliers of materials and components, it is essential to select pertinent rather than complex test procedures.