Biological Evaluation Of Medical Devices Research Articles

Bioresorption and Biomineralization of S53P4 Bioactive Glass in Neutral Tris Buffer and Citric Acid Solution.

In this study, S53P4 (53SiO2-23Na2O-20CaO-4P2O5) bioactive glass (BG) were prepared through a melt-milling process, and their bioresorption and biomineralization behavior was evaluated by in vitro dissolution under different solution conditions (neutral and acidic). The particle size of S53P4 BG was controlled by milling, and the in vitro dissolution evaluation was performed in tris buffer and citric acid solution for 21 days at 37 °C according to ISO 10993-14 (biological evaluation of medical devices). During dissolution, the ion release rate of S53P4 BG was confirmed to be three times faster in citric acid solution than that in tris buffer. Among them, the ion concentration of calcium and phosphorus initially increased and then gradually decreased, which is due to the biomineralization process. This process formed a new layer of particles on the surface of S53P4 BG, which was identified as a calcium-phosphate-based compound by X-ray diffraction analysis. Furthermore, the thickness of the layer was observed to be 273 nm in tris buffer and 34 nm in citric acid solution by focused-ion beam scanning electron microscopy, and the morphology of the particles comprising this layer was observed to be thicker and longer in tris buffer than that in citric acid solution. This difference is due to the citrate present in the citric acid solution interacting with the released calcium ions and inhibiting the formation of a new layer. Thus, the ion release of S53P4 BG was faster in citric acid solution than that in tris buffer, but the biomineralization process to form the calcium phosphate-based compound was more effective in tris buffer.

Preparation and Performance Study of a Novel Antibacterial Hemostatic Chitosan Sponge

To create a novel chitosan antibacterial hemostatic sponge (NCAHS) and to evaluate its material and biological properties. Chitosan, a polysaccharide, was used as the sponge substrate and different proportions of sodium tripolyphosphate (STPP), glycerol, and phenol sulfonyl ethylamine were added to prepare the sponges through the freeze-drying method. The whole-blood coagulation index (BCI) was used as the screening criterion to determine the optimal concentrations of chitosan and the other additives and the hemostatic sponges were prepared accordingly. Zein/calcium carbonate (Zein/CaCO3) composite microspheres loaded with ciprofloxacin hydrochloride were prepared and added to the hemostatic sponges to obtain NCAHS. Scanning electron microscope was used to observe the microscopic morphology and porosity of the NCAHS. The water absorption rate, in vitro antibacterial susceptibility rate against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), in vitro coagulation performance, and hemocompatibility of NCAHS were examined. The coagulation performance of NCAHS was evaluated by using rabbit liver injury and rabbit auricular artery hemorrhageear models and commercial hemostatic sponge (CHS) was used as a control. The in vivo biocompatibility, including such aspects as cytotoxicity, skin irritation in animals, and acute in vivo toxicity, of the NCAHS extracts was examined by using as a reference the national standards for biological evaluation of medical devices. The NCAHS prepared with 1.5% chitosan (W/V), 0.01% STPP (W/V), 0% glycerol (V/V), 0.15% phenol-sulfonyl-ethylamine (V/V), Zein and CaCO3 at the mixing ratio of 5∶1 (W/W), Zein at the final mass concentration of 2.5 g/L, and ethanol at the final concentration of 17.5% (V/V) were fine and homogeneous, possessing a honeycomb-like porous structure with a pore size of about 200 μm. The NCAHS thus prepared had the lowest BCI value. The water absorption ([2362.16±201.15] % vs. [1102.56±91.79]%) and in vitro coagulation performance (31.338% vs. 1.591%) of NCAHS were significantly better than those of CHS (P<0.01). Tests with the in vivo auricular artery hemorrhage model ([36.00±13.42] s vs. [80.00±17.32] s) and rabbit liver bleeding model ([30.00±0] s vs. [70.00±17.32] s) showed that the hemostasis time of NCAHS was significantly shorter than that of CHS (P<0.01). NCAHS had significant inhibitory ability against S. aureus and E. coli. In addition, NCAHS showed good in vitro and in vivo biocompatibility. NCAHS is a composite sponge that shows excellent antimicrobial properties, hemostatic effect, and biocompatibility. Therefore, its extensive application in clinical settings is warranted.

The Biocompatibility of a New Type of 45S5 Bioactive Graft in a Sheep Model: A Pilot Study.

Background Bone is a dramatically regenerating tissue with the ability to heal after trauma, although intensive surgical management is required to treat considerable damage. In this study, 45S5 bioactive grafts were prepared through the melt-quenched method in compliance with the guidelines on medical product requirements (MDD regulations; 93/42/EEC Annex-II section 3&4 and ISO standardizations; ISO 13485:2016) for bone repair and regeneration. Methodology After preparing the graft/scaffold, it was evaluated for biocompatibility according to the principles of "lSO 10993-6 2015 Biological evaluation of medical devices: Tests for local effects after implantation, Annex D 'Test method for implantation in bone,'" "lSO 10993-2:2005 Biological evaluation of medical devices: Animal welfare requirements," and "lSO 10993-12 2012 Biological evaluation of medical devices sample preparation rules and standards." Defects were created on the tibia of the right hind leg. The defects were filled with 3-mm bioactive granules, and a cylindrical polypropylene biocompatible material was used as a negative control. After 120 days, the sheep were sacrificed, and the tibia were analyzed. Results The results demonstrated the safety of 45S5 bioactive grafts. Histological evaluation showed no signs of pathological changes around the implant area. Hematoxylin and eosin sections demonstrated the presence of a few multinucleated giant cells, macrophages, and non-irritantmild fibrotic changes on the surface of the biomaterial. Conclusions 45S5 bioactive glass was found to be biocompatible in a sheep model, demonstrating its capacity to promote bone consolidation while also justifying its further preclinical applicationas a bone-bonded material owing to the layer formation of the growing bone mineral.

Toxic or not toxic? The specifications of the standard ISO 10993-5 are not explicit enough to yield comparable results in the cytotoxicity assessment of an identical medical device.

Medical device manufacturers are obliged to prove the biocompatibility of their products when they come into contact with the human body. The requirements for the biological evaluation of medical devices are specified by the international standard series ISO 10993. Part five of this series describes the performance of in vitro cytotoxicity tests. This test evaluates the effects of medical device use on cell health. The existence of the specific standard suggests that the tests will produce reliable and comparable results. However, the ISO 10993-5 offers wide latitude in the test specifications. In the past, we noticed inconsistencies of the results from different laboratories. To determine if the specifications of the standard ISO 10993-5 are explicit to ensure the comparability of test results and, if not, identify potential influencing factors. An interlaboratory comparison was conducted for the in vitro cytotoxicity test according to ISO 10993-5. Fifty-two international laboratories evaluated the cytotoxicity for two unknown samples. One was polyethylene (PE) tubing, which is expected to be non-cytotoxic and the other was polyvinyl chloride (PVC) tubing, for which a cytotoxic potential was presumed. All laboratories were asked to perform an elution test with predefined extraction specifications. The other test parameters were freely chosen by the laboratories according to the guidelines set by the standard. To our surprise only 58 percent of the participating laboratories identified the cytotoxic potential of both materials as expected. Particularly for PVC a considerable variation of the results between the laboratories was observed [mean = 43 ± 30 (SD), min = 0, max = 100]. We showed that ten percent serum supplementation to the extraction medium, as well as longer incubation of the cells with the extract, greatly increased the test sensitivity for PVC. The results clearly show that the specifications set by the ISO 10993-5 are not explicit enough to obtain comparable results for an identical medical device. To set requirements that ensure reliable cytotoxicity assessments, further research will be necessary to identify the best test conditions for specific materials and/or devices and the standard needs to be revised accordingly.

Pre-Clinical Requirements for Drug-Eluting Stents for CE Certification

Abstract: Drug Eluting Stents (DES) are small, expandable tubes that are implanted into a diseased, blocked peripheral or coronary artery through angioplasty to widen and increase the blood flow by slowly releasing the drug from device. They are covered in a medication that stops scar tissue from expanding upon that artery. In medical practice DES are frequently used for vascular disorders, exhibiting adequate potency and suitability within the acceptable range. Medical device regulations in European Union (EU) are covered by Directives 93/42/EEC, 98/79/EEC and 90/385/EEC which were recently replaced by new regulations (EU) 2017/745 on medical devices and (EU) 2017/746 on In vitro diagnostic medical devices. Across all the EU legislation, “CE Mark” or “Certificate of Compliance” has become a recognised term. The Competent authority’s (CA) certifies that a product conforms to required standards of EU, then the manufacturer display the “CE mark” on the label. The DrugDevice combination products like DES are included in Class-III high risk active implantable medical devices. The pre-clinical investigations of drug eluting stents often follow International Organization for Standardization (ISO) requirements, these vascular stents are covered under ISO 25539-2: 2020 - Cardiovascular Implants - Endovascular Devices, ISO 10993:2018- Biological Evaluation of Medical Devices and ISO 10555-1: 2013 – Intravascular catheters, sterile and single use medical devices.

Extraction and Characterization of Pepsin- and Acid-Soluble Collagen from the Swim Bladders of Megalonibea fusca.

There is a growing demand for the identification of alternative sources of collagen not derived from land-dwelling animals. The present study explored the use of pepsin- and acid-based extraction protocols to isolate collagen from the swim bladders of Megalonibea fusca. After extraction, these acid-soluble collagen (ASC) and pepsin-soluble collagen (PSC) samples respectively were subjected to spectral analyses and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) characterization, revealing both to be comprised of type I collagen with a triple-helical structure. The imino acid content of these ASC and PSC samples was 195 and 199 residues per 1000 residues, respectively. Scanning electron microscopy demonstrated that samples of freeze-dried collagen exhibited a compact lamellar structure, while transmission electron microscopy and atomic force microscopy confirmed the ability of these collagens to undergo self-assembly into fibers. ASC samples exhibited a larger fiber diameter than the PSC samples. The solubility of both ASC and PSC was highest under acidic pH conditions. Neither ASC nor PSC caused any cytotoxicity when tested in vitro, which met one of the requirements for the biological evaluation of medical devices. Thus, collagen isolated from the swim bladders of Megalonibea fusca holds great promise as a potential alternative to mammalian collagen.

Cytotoxicity Evaluation of Hydrogel Sheet Dressings Fabricated by Gamma Irradiation: Extract and Semi-Direct Contact Tests

Cytotoxicity presents one of the required criteria in the biological evaluation of medical devices. In this study, the semi-direct contact test was used to evaluate the potential cytotoxicity of hydrogel wound dressings compared to the conventional extract test. Three types of hydrogel sheets were fabricated from poly(vinyl alcohol) (PVA) by gamma irradiation: Bare sheets, silver (Ag)-coated sheets, and Aloe vera (AV)-coated sheets. In the extract test, L929 cells were cultured in the extract derived from the elution of hydrogel samples. For the semi-direct contact test, the cells were cultured in situ with the hydrogel samples placed inside transwell inserts above the cell monolayers. At the endpoint of both tests, MTT assay was performed, and the cell viability was determined from the absorbance of formazan. Only the bare and AV-coated hydrogel sheets showed cell viability above the 70 % threshold that ensured the non-cytotoxicity by both tests. For Ag-coated sheets, less than 70 % cell viability occurred when Ag coating was ³ 0.2 mg/cm2. Interestingly, the formazan-depleted area underneath the Ag-coated sample could be clearly observed by the semi-direct contact test. The release of Ag in the form of nanoparticles was confirmed by UV-Vis absorption at 420 nm. In conclusion, the semi-direct contact test can serve as a reliable alternative to the conventional extract test in evaluating the potential cytotoxicity of hydrogel wound dressings.&#x0D; HIGHLIGHTS&#x0D; &#x0D; A semi-direct contact test with transwell inserts was investigated as an alternative approach to the conventional extract test in evaluating the cytotoxicity of hydrogel wound dressings&#x0D; Leachable substances from the hydrogel dressings permeated through the porous membrane of transwell inserts to the reach the cell monolayer underneath&#x0D; Cell viability results based on MTT assay obtained from semi-direct contact test were in agreement with the extract test&#x0D; Only the semi-direct contact test provided the visual assessment of localized toxicity caused by the release of silver nanoparticles from hydrogel sheets onto the cell monolayer&#x0D; &#x0D; GRAPHICAL ABSTRACT

Immunological response of polysaccharide nanogel-incorporating PEG hydrogels in an in vivo diabetic model

Cell-based therapies hold significant advantages in comparison with the traditional drug-based or injection-based treatments. However, for long-term functional cellular implants, immune acceptance must be established. To accomplish the acceptance of the implanted cells, various biomaterial systems have been studied. Nanogels have shown great potential for modulation of cellular microenvironments, acting as a physical barrier between the immune system and the implant. However, internalization of nano-scale materials by implanted cells is not desirable and is yet to be overcome. In this study, we incorporated acrylate modified cholesterol-bearing pullulan (CHPOA) nanogels into poly (ethylene glycol) diacrylate (PEGDA) hydrogels through covalent crosslinking, where we used visible light-induced photopolymerization. We characterized morphology and swelling properties of CHPOA incorporated PEG composite hydrogels using FE-SEM and gravimetric analysis. Also, we investigated the biocompatibility properties of composite hydrogels in vivo, where we used both healthy and diabetic mice. We induced diabetes in mice using a low dose streptozotocin (STZ) injections and implanted composite hydrogels in both diabetic and healthy mice through subcutaneous route. Immune cell infiltration of the retrieved tissue was examined through histological analysis, where we observed minimum immune response levels of 0–2 rareness, according to ISO standard of biological evaluation of medical devices. Our observation suggests that the composite hydrogel developed here can be used to introduce nanostructured domains into bulk hydrogels and that this system has potential to be used as immunologically acceptable composite material in cellular therapy without internalization of nanoparticles.

Biological Evaluation of Medical Devices in the Form of Suppositories for Rectal and Vaginal Use

Background. Programs of preclinical safety studies of the health care products depend on the regulatory status of the investigated products. The classification of such products, in particular suppositories for rectal and vaginal use, is a critical step of developing tactics for their biological evaluation. Adaptation of biological evaluation methods for the medical devices based on the combination of biologically active substances, as well as evaluation of the results of such studies is urgent task of biomedicine. Objective. To substantiate the regulatory status and to carry out a biological evaluation of medical devices in the form of vaginal suppositories based on octenidine dihydrochloride ("Prodexyn") and in the form of rectal suppositories based on Saw palmetto, Levisticum officinale and Calendula officinalis extracts ("Pravenor"). Methods. Biological evaluation was conducted according to the requirements of ISO 10993 standards using in vitro and in vivo biological test systems (cytotoxicity in cell culture and the MTT test, sensitizing and irritating effect in guinea pigs). Results. The cytotoxicity (СС50) of the medical device "Prodexyn" extract in Vero cell culture was 8.35 μg/ml calculated as octenidine dihydrochloride and 416.65 μg/ml calculated as dexpanthenol. "Pravenor" medical device was found to be non-toxic in Vero cell culture. According to the results of MMT assay CC50 for octenidine dihydrochloride was 1.67 μg/ml, and 83.33 μg/ml – for dexpanthenol. CC50 indicators calculated for the different active ingredients of the medical device "Pravenor" were the following: 50 mg/ml for the dwarf palm berries extract (Saw palmetto), 16.67 mg/ml for the lovage roots extract (Levisticum officinale), and 16.67 mg/ml for the calendula flowers extract (Calendula officinalis). No sensitizing or skin irritating effects were observed in guinea pigs. Conclusions. Biological evaluation of medical devices in the form of rectal suppositories "Pravenor" and vaginal suppositories "Prodexyn" performed using in vitro and in vivo biological systems. It was demonstrated an acceptable level of safety of the products. The MTT test was 5 times more sensitive than the Vero cell culture method in determination of cytotoxicity.

Safety of Alginate-based Gastric Mucosal Protective Adhesive and Feasibility Study of Its Use as Submucosal Injection

To study the safety of alginate based gastric mucosal protective adhesive and its feasibility as a submucosal injection. The feasibility of using alginate-based gastric mucosal protective gel as submucosal injection was evaluated by in vitro gastric mucosal uplift test in pigs and in vivo gastric mucosal uplift test in rats. The safety of alginate based gastric mucosa protective adhesive was evaluated by cytotoxicity test, acute toxicity test and oral mucosa stimulation test according to GB/T 16886 series standard of biological evaluation of medical devices. After injection of different concentrations of alginate base mucosal protective adhesive solution, the uplift height was significantly higher than that of normal saline (P<0.05). Gastric mucosal protection glue has no cytotoxic oral mucosal irritation or acute toxicity. Gastric mucosa protector is a promising new medical device product with feasibility and good biocompatibility as submucosal uplift injection agent.

Photoelectric Dye, NK-5962, as a Potential Drug for Preventing Retinal Neurons from Apoptosis: Pharmacokinetic Studies Based on Review of the Evidence.

NK-5962 is a key component of photoelectric dye-based retinal prosthesis (OUReP). In testing the safety and efficacy, NK-5962 was safe in all tests for the biological evaluation of medical devices (ISO 10993) and effective in preventing retinal cells from death even under dark conditions. The long-term implantation of the photoelectric dye-coupled polyethylene film in the subretinal space of hereditary retinal dystrophic (RCS) rats prevented neurons from apoptosis in the adjacent retinal tissue. The intravitreous injection of NK-5962 in the eyes of RCS rats, indeed, reduced the number of apoptotic cells in the retinal outer nuclear layer irrespective of light or dark conditions. In this study, we reviewed the in vitro and in vivo evidence of neuroprotective effect of NK-5962 and designed pharmacokinetic experiments. The in vitro IC50 of 1.7 μM, based on the protective effect on retinal cells in culture, could explain the in vivo EC50 of 3 μM that is calculated from concentrations of intravitreous injection to prevent retinal neurons from apoptosis. Pharmacokinetics of NK-5962 showed that intravenous administration, but not oral administration, led to the effective concentration in the eye of rats. NK-5962 would be a candidate drug for delaying the deterioration of retinal dystrophy, such as retinitis pigmentosa.

In vitro and In vivo Biocompatibility Evaluation of Freeze Dried Gelatin Haemostat

Gelatin sponges developed by crosslinking gelatin with formaldehyde followed by controlled freeze-drying results in soft, spongy porous structures, which are useful in arresting bleeding during surgical procedures. The aim of this article is to conduct the in vivo evaluation of the gelatin sponge as per ISO 10993: Biological evaluation of medical devices; and prove its biocompatibility. The sponges were also evaluated by morphology analysis, tensile strength and blood-absorption studies. Sponges were found to be microporous with considerable mechanical strength to withstand any rupture during its application. Blood absorption studies showed good absorption behaviour. As per ISO 10993; cytotoxicity, skin irritation, sensitisation and blood compatibly studies has to be conducted to check the biocompatibility of a biomaterial. Gelatin sponge was found to be non-cytotoxic in Balb/c 3T3 cells. The experiments conducted on albino rabbits and guinea pig concluded that the material does not cause any irritation and sensitisation in vivo and is non-haemolytic when in contact with blood. Hence the material meets the requirements of a biocompatible haemostatic agent for the management of blood loss during surgical procedures.

Characterization of Bio-Inspired Electro-Conductive Soy Protein Films.

Protein-based conductive materials are gaining attention as alternative components of electronic devices for value-added applications. In this regard, soy protein isolate (SPI) was processed by extrusion in order to obtain SPI pellets, subsequently molded into SPI films by hot pressing, resulting in homogeneous and transparent films, as shown by scanning electron microscopy and UV-vis spectroscopy analyses, respectively. During processing, SPI denatured and refolded through intermolecular interactions with glycerol, causing a major exposition of tryptophan residues and fluorescence emission, affecting charge distribution and electron transport properties. Regarding electrical conductivity, the value found (9.889 × 10−4 S/m) is characteristic of electrical semiconductors, such as silicon, and higher than that found for other natural polymers. Additionally, the behavior of the films in contact with water was analyzed, indicating a controlled swelling and a hydrolytic surface, which is of great relevance for cell adhesion and spreading. In fact, cytotoxicity studies showed that the developed SPI films were biocompatible, according to the guidelines for the biological evaluation of medical devices. Therefore, these SPI films are uniquely suited as bioelectronics because they conduct both ionic and electronic currents, which is not accessible for the traditional metallic conductors.

Photoelectric dye-based retinal prosthesis (OUReP) as a novel type of artificial retina

We have developed the world's first novel type of artificial retina, OUReP (Okayama University Retinal Prosthesis), in which a photoelectric dye that converts light energy into electric potential is covalently bonded to the surface of a polyethylene thin film as an insulator. The receptor that absorbs light and the output device that generates displacement current to stimulate nearby neurons are integrated in a sheet of thin film. It has become possible to measure the surface potential of the artificial retina OUReP using a Kelvin probe that measures the surface potential of semiconductors. When light is turned on and off to the artificial retina OUReP, the surface potential changes rapidly. As the light intensity is increased, the potential change on the surface of the artificial retina becomes larger. As for safety, the artificial retina OUReP was not toxic in all tests for biological evaluation of medical devices. As for efficacy, the artificial retina OUReP was implanted under the retina by vitreous surgery in monkey eyes which had chemically-induced macular degeneration with photoreceptor cell loss. Over the next 6 months, retinal detachment did not occur during the course, and the artificial retina was in contact with the retinal tissue. The amplitude of the visual evoked potential attenuated by macular degeneration recovered 1 month after implantation of the artificial retina, and the recovery of amplitude was maintained until 6 months after the implantation. By using multielectrode array-mounted dish recording system, it has been proved that action potential spikes are induced when the artificial retina is placed on degenerative retinal tissue of retinal dystrophic rats or mice and exposed to light, which is used as an index of the effectiveness of the artificial retina. We have established manufacturing and quality control of the device in a clean room facility, proved the safety and efficacy, and are preparing for first-in-human investigator-initiated clinical trials.

Evaluation of Antibacterial and Cytotoxic Properties of a Fluorinated Diamond-Like Carbon Coating for the Development of Antibacterial Medical Implants.

Peri-implant infection is a serious complication in surgical procedures involving implants. We conducted an in vitro study to determine whether the use of a fluorinated diamond-like carbon (F-DLC) coating on a titanium alloy surface can prevent peri-implant infection. After applying the F-DLC, we evaluated its antibacterial and cytotoxic properties. The coating groups, containing controlled fluorine concentrations of 5.44%, 17.43%, 24.09%, and 30%, were examined for the presence of Staphylococcus aureus and Escherichia coli according to ISO 22196 for the measurement of antibacterial activity on plastics and other nonporous surfaces. Biological toxicity was evaluated using Chinese hamster V79 cells according to ISO 10993-5 for the biological evaluation of medical devices. In the control group, populations of S. aureus and E. coli substantially increased from 2.4 × 104 to (1.45 ± 1.11) × 106 colony-forming units (CFUs) and from 2.54 × 104 to (4.04 ± 0.44) × 106 CFUs, respectively. However, no bacteria colonies were detected in any F-DLC group with a fluorine concentration of ≥ 17.43%. In the biological toxicity study, an F-DLC coating with a fluorine concentration of 30% showed a colony formation rate of 105.8 ± 24.1%, which did not differ significantly from the colony formation rate of 107.5 ± 31.1% in the nontoxic control group. An F-DLC coating on titanium alloy discs showed excellent in vitro antibacterial activity with no biological toxicity.

Effect of ions concentration in buffer solutions on the nucleation of hydroxyapatite surface on the octacalcium phosphate granules

Octacalcium phosphate granules were subsequently immersed for different lengths of time from 1 day to 44 days at constant temperature 37±0.4°C in solutions, simulating the extracellular body fluids: Supersaturated Calcification Solution (SCS), Simulated Body Fluid (SBF), based on the ISO-10993 “Biological Evaluation of Medical Devices” standard. The role of buffer`s systems pH-value, time of the material exposure and calcium and phosphorus ionic concentrations were analysed with the main focus on kinetics of degradation, changes in the morphological characteristics and phase composition of octacalcium phosphate samples.

Basic Approach of Biological Evaluation of Medical Devices for Pre-Market Applications

Basic Approach of Biological Evaluation of Medical Devices for Pre-Market Applications

Ruthenium oxide based microelectrode arrays for in vitro and in vivo neural recording and stimulation

We have characterized the in vitro and in vivo extracellular neural recording and stimulation properties of ruthenium oxide (RuOx) based microelectrodes. Cytotoxicity and functional neurotoxicity assays were carried out to confirm the in vitro biocompatibility of RuOx. Material extract assays, in accordance to ISO protocol “10993-5: Biological evaluation of medical devices”, revealed no significant effect on neuronal cell viability or the functional activity of cortical networks. In vitro microelectrode arrays (MEAs), with indium tin oxide (ITO) sites modified with sputtered iridium oxide (IrOx) and RuOx in a single array, were developed for a direct comparison of electrochemical and recording performance of RuOx to ITO and IrOx deposited microelectrode sites. The impedance of the RuOx-coated electrodes measured by electrochemical impedance spectroscopy was notably lower than that of ITO electrodes, resulting in robust extracellular recordings from cortical networks in vitro. We found comparable signal-to-noise ratios (SNRs) for RuOx and IrOx, both significantly higher than the SNR for ITO. RuOx-based MEAs were also fabricated and implanted in the rat motor cortex to demonstrate manufacturability of the RuOx processing and acute recording capabilities in vivo. We observed single-unit extracellular action potentials with a SNR >22, representing a first step for neurophysiological recordings in vivo with RuOx based microelectrodes. Statement of significanceA critical challenge in neural interface technology is the development of microelectrodes that have recording and electrical stimulation capabilities suitable for bidirectional communication between the external electronic device and the nervous system. The present study explores the feasibility and functional capabilities of ruthenium oxide microelectrodes as a neural interface. Significant improvement in electrochemical properties and neuronal recordings are reported when compared to commercially available indium tin oxide and was similar to that of iridium oxide electrodes. The data demonstrate the potential for future development of chronic neural interfaces using ruthenium oxide based microelectrodes for recording and stimulation.

Comparative Safety Testing (acute systemic toxicity in mice) of Two Materials Prepared from Polypropylene-Polyester (Codubix S) or Acrylate Resin (Mendec Cranio) Used for the Manufacturing of a Calvaria Prosthesis

The aim of the study was a comparison of the acute toxicity of two popular prostheses used in the reconstruction of the bones of the skull. For the tests, the following materials were used: a polypropylene-polyester knitted Codubix S cranial bone prosthesis, made by TRICOMED SA, and polymethyl methacrylate Mednec Cranio resin. The tests were carried out in accordance with the following standards – PN-EN ISO 10993-11:2009 Biological evaluation of medical devices - Part 11: Tests for systemic toxicity, and PN-EN ISO 10993-12:2012 Biological evaluation of medical devices – Part 12: Sample preparation and reference materials. During the evaluation, adult male and female Balb/c mice were used. The animals were injected intravenously using extracts of both materials in 0.9% NaCl and intraperitoneally with the same extracts in sesame oil. The tests lasted 7 days, during which the health of the animals and their behavior were assessed. Both in the control and test groups, there was no mortality of the animals, and the health and behaviour of mice were unchanged when compared with the normal. After 7 days the internal organs of the chest and abdominal cavity of the animals were subjected to macroscopic pathomorphological examination, during which no changes indicating the toxic action of Codubix S and Mednec Cranio resin were found. Before the acute systemic toxicity tests, the chemical purity of both implants was assessed. The chemical purity of a product is one of the factors determining its biological properties. A product which is characterised by a higher degree of chemical purity contains fewer substances which may have a negative impact on biological reactions. Both prostheses meet the requirements of purity for medical devices.

Identification of the degradation products of a crosslinked polyester using LC-MS

In the process of developing new biomedical devices, in addition to meeting the required criteria for their intended applications, it is imperative to also identify the degradation products over the lifetime of their intended use. Determining the major degradation products from a device is an important consideration when completing the biological evaluation of medical devices under the ISO 10993 series guidelines. Furthermore, adequate identification of the degradation products may provide preliminary insights into potentially toxic products that may arise as the device degrades.We developed a method that can be used to identify the degradation products of a polyester intended to be used as a medical device. A biodegradable polyester prepared from thiomalic acid, 1,8-octanediol and maleic acid and its nitric oxide (NO)-releasing analogue degraded over a 10-week period was used as a model system. Using a reproducible liquid chromatography-mass spectrometry (LC-MS) method, we resolved and identified major component over the degradation process. Our method highlights the advantages of using LC-MS to accurately identify the components of degradation and provides a framework for future biomedical device studies.