Polymeric Medical Devices Research Articles

Revealing the glass transition in shape memory polymers using Brillouin spectroscopy.

Emerging medical devices which employ shape memory polymers (SMPs) require precise measurements of the glass transition temperature (Tg) to ensure highly controlled shape recovery kinetics. Conventional techniques like differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) have limitations that prevent utilization for certain devices, including limited accuracy and the need for sacrificial samples. In this report, we employ an approach based on Brillouin spectroscopy to probe the glass transition of SMPs rapidly, remotely, and nondestructively. Further, we compare the Tg obtained from Brillouin scattering with DMA- and DSC-measured Tg to demonstrate the accuracy of Brillouin scattering for this application. We conclude that Brillouin spectroscopy is an accurate technique for obtaining the glass transition temperature of SMPs, aligning closely with the most common laboratory standards while providing a rapid, remote, and nondestructive method for the analysis of unique polymeric medical devices.

Conservative Exposure Predictions for Rapid Risk Assessment of Phase-Separated Additives in Medical Device Polymers

A novel approach for rapid risk assessment of targeted leachables in medical device polymers is proposed and validated. Risk evaluation involves understanding the potential of these additives to migrate out of the polymer, and comparing their exposure to a toxicological threshold value. In this study, we propose that a simple diffusive transport model can be used to provide conservative exposure estimates for phase separated color additives in device polymers. This model has been illustrated using a representative phthalocyanine color additive (manganese phthalocyanine, MnPC) and polymer (PEBAX 2533) system. Sorption experiments of MnPC into PEBAX were conducted in order to experimentally determine the diffusion coefficient, D=(1.6±0.5)×10-11cm2/s, and matrix solubility limit, C s=0.089wt.%, and model predicted exposure values were validated by extraction experiments. Exposure values for the color additive were compared to a toxicological threshold for a sample risk assessment. Results from this study indicate that a diffusion model-based approach to predict exposure has considerable potential for use as a rapid, screening-level tool to assess the risk of color additives and other small molecule additives in medical device polymers.

Antimicrobial Treatment of Polymeric Medical Devices by Silver Nanomaterials and Related Technology.

Antimicrobial biocompatible polymers form a group of highly desirable materials in medicinal technology that exhibit interesting thermal and mechanical properties, and high chemical resistance. There are numerous types of polymers with antimicrobial activity or antimicrobial properties conferred through their proper modification. In this review, we focus on the second type of polymers, especially those whose antimicrobial activity is conferred by nanotechnology. Nanotechnology processing is a developing area that exploits the antibacterial effects of broad-scale compounds, both organic and inorganic, to form value-added medical devices. This work gives an overview of nanostructured antimicrobial agents, especially silver ones, used together with biocompatible polymers as effective antimicrobial composites in healthcare. The bactericidal properties of non-conventional antimicrobial agents are compared with those of conventional ones and the advantages and disadvantages are discussed.

Improving risk assessment of color additives in medical device polymers.

Many polymeric medical device materials contain color additives which could lead to adverse health effects. The potential health risk of color additives may be assessed by comparing the amount of color additive released over time to levels deemed to be safe based on available toxicity data. We propose a conservative model for exposure that requires only the diffusion coefficient of the additive in the polymer matrix, D, to be specified. The model is applied here using a model polymer (poly(ether-block-amide), PEBAX 2533) and color additive (quinizarin blue) system. Sorption experiments performed in an aqueous dispersion of quinizarin blue (QB) into neat PEBAX yielded a diffusivity D = 4.8 × 10-10 cm2 s-1 , and solubility S = 0.32 wt %. On the basis of these measurements, we validated the model by comparing predictions to the leaching profile of QB from a PEBAX matrix into physiologically representative media. Toxicity data are not available to estimate a safe level of exposure to QB, as a result, we used a Threshold of Toxicological Concern (TTC) value for QB of 90 µg/adult/day. Because only 30% of the QB is released in the first day of leaching for our film thickness and calculated D, we demonstrate that a device may contain significantly more color additive than the TTC value without giving rise to a toxicological concern. The findings suggest that an initial screening-level risk assessment of color additives and other potentially toxic compounds found in device polymers can be improved. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 310-319, 2018.

併用薬剤によるプラスチック製医療機器の破損を予測する簡易試験法の開発

併用薬剤によるプラスチック製医療機器の破損を予測する簡易試験法の開発

High-throughput Identification of Bacteria Repellent Polymers for Medical Devices.

Medical devices are often associated with hospital-acquired infections, which place enormous strain on patients and the healthcare system as well as contributing to antimicrobial resistance. One possible avenue for the reduction of device-associated infections is the identification of bacteria-repellent polymer coatings for these devices, which would prevent bacterial binding at the initial attachment step. A method for the identification of such repellent polymers, based on the parallel screening of hundreds of polymers using a microarray, is described here. This high-throughput method resulted in the identification of a range of promising polymers that resisted binding of various clinically relevant bacterial species individually and also as multi-species communities. One polymer, PA13 (poly(methylmethacrylate-co-dimethylacrylamide)), demonstrated significant reduction in attachment of a number of hospital isolates when coated onto two commercially available central venous catheters. The method described could be applied to identify polymers for a wide range of applications in which modification of bacterial attachment is important.

High-throughput Identification of Bacteria Repellent Polymers for Medical Devices

Medical devices are often associated with hospital-acquired infections, which place enormous strain on patients and the healthcare system as well as contributing to antimicrobial resistance. One possible avenue for the reduction of device-associated infections is the identification of bacteria-repellent polymer coatings for these devices, which would prevent bacterial binding at the initial attachment step. A method for the identification of such repellent polymers, based on the parallel screening of hundreds of polymers using a microarray, is described here. This high-throughput method resulted in the identification of a range of promising polymers that resisted binding of various clinically relevant bacterial species individually and also as multi-species communities. One polymer, PA13 (poly(methylmethacrylate-co-dimethylacrylamide)), demonstrated significant reduction in attachment of a number of hospital isolates when coated onto two commercially available central venous catheters. The method described could be applied to identify polymers for a wide range of applications in which modification of bacterial attachment is important.

Effects of Terminal Sterilization on PEG-Based Bioresorbable Polymers Used in Biomedical Applications.

The effects of ethylene oxide (EO), vaporized hydrogen peroxide (VHP), gamma (γ) radiation, and electron-beam (E-beam) on the physiochemical and morphological properties of medical device polymers are investigated. Polymers with ether, carbonate, carboxylic acid, amide and ester functionalities are selected from a family of poly(ethylene glycol) (PEG) containing tyrosine-derived polycarbonates (TyrPCs) to include slow, medium, fast, and ultrafast degrading polymers. Poly(lactic acid) (PLA) is used for comparison. Molecular weight (Mw) of all tested polymers decreases upon gamma and E-beam, and this effect becomes more pronounced at higher PEG content. Gamma sterilization increases the glass transition temperature of polymers with high PEG content. EO esterifies the carboxylic acid groups in desaminotyrosol-tyrosine (DT) and causes significant degradation. VHP causes hydroxylation of the phenyl ring, and hydrolytic degradation. This study signifies the importance of the chemical composition when selecting a sterilization method, and provides suggested conditions for each of the sterilization methods.

Properties and Applications of Polyvinyl Alcohol, Halloysite Nanotubes and Their Nanocomposites

The aim of this review was to analyze/investigate the synthesis, properties, and applications of polyvinyl alcohol–halloysite nanotubes (PVA–HNT), and their nanocomposites. Different polymers with versatile properties are attractive because of their introduction and potential uses in many fields. Synthetic polymers, such as PVA, natural polymers like alginate, starch, chitosan, or any material with these components have prominent status as important and degradable materials with biocompatibility properties. These materials have been developed in the 1980s and are remarkable because of their recyclability and consideration of the natural continuation of their physical and chemical properties. The fabrication of PVA–HNT nanocomposites can be a potential way to address some of PVA’s limitations. Such nanocomposites have excellent mechanical properties and thermal stability. PVA–HNT nanocomposites have been reported earlier, but without proper HNT individualization and PVA modifications. The properties of PVA–HNT for medicinal and biomedical use are attracting an increasing amount of attention for medical applications, such as wound dressings, drug delivery, targeted-tissue transportation systems, and soft biomaterial implants. The demand for alternative polymeric medical devices has also increased substantially around the world. This paper reviews individualized HNT addition along with crosslinking of PVA for various biomedical applications that have been previously reported in literature, thereby showing the attainability, modification of characteristics, and goals underlying the blending process with PVA.

Prebiotic-chemistry inspired polymer coatings for biomedical and material science applications

In the field of prebiotic chemistry, hydrogen cyanide (HCN)-derived polymers have been studied for many years as a possible source of the precursors that provide the building blocks for proteins as well as nucleic acids, and they have also been associated with the origin of life. The HCN trimer, aminomalononitrile (AMN), polymerizes to give a brown complex nitrogenous polymer. We report the one-step polymerization-deposition of AMN as a simple generic surface-coating method and as an application of prebiotic chemical research to material science. We found that this polymerization, carried out in buffered aqueous solutions, can be used to coat a wide range of organic and inorganic substrate materials. The robust, non-cytotoxic coatings also provide for excellent cell attachment, suggesting potential biomedical applications. Furthermore, the coating chemistry allows for the immobilization of other compounds, including metals, both during coating formation or by performing secondary immobilization reactions. Australian researchers have transformed molecules associated with the origin of life into biocompatible polymers for medical devices. Hydrogen cyanide is a so-called prebiotic chemical that researchers believe acted as a building block for peptide and protein generation during Earth's early history. Richard Evans from Australia's national science agency CSIRO and co-workers developed a simple procedure that spontaneously turns aminomalonitrile, a hydrogen cyanide trimer, into a sticky brown polymer using pH-buffered water. A one-step immersion process then coated a wide range of substrates — glass, plastics and metals — with a robust film having desirable device characteristics. Cell growth experiments showed successful attachment of mouse fibroblasts to the coating with no cytotoxicity. The team also immobilized metals and organic labelling compounds onto the coating using co-polymerization and post-film treatment strategies. We report a generic aqueous coating methodology that provides highly biocompatible surfaces. The method is inspired by prebiotic chemistry that involves the polymerization of hydrogen cyanide (HCN). The neutralization of the commercially available HCN trimer aminomalononitrile toluenesulfonate results in spontaneous polymerization that can be used to coat a wide variety of surfaces with a highly nitrogenous polymer. The non-cytotoxic coating provides excellent cell attachment and its chemistry allows the immobilization of other compounds including metals both during coating formation or by subsequent secondary immobilization reactions. This gives access to bioactive coatings including antimicrobial surfaces. Prebiotic chemistry has always been focussed on the understanding of the chemical origin of life and has remained highly fundamental research. To our knowledge this is the first application of prebiotic chemistry to material science.

Ageing processes in laser sintered and injection moulded PA12 following hygienic reprocessing

Purpose– The purpose of this paper is to describe the ageing behaviour of polyamide 12 (PA12) after clinical use. The research is focused on the comparison of the processing methods injection moulding and laser sintering.Design/methodology/approach– Test specimens are subjected to a cyclic stress of defined bending, cleaning, disinfection and sterilization. The focus of interest in this research is the degradation and reduction of mechanical properties.Findings– Mechanical and optical changes of the materials after clinical use and hygienic reprocessing are evaluated and discussed.Research limitations/implications– This article is focused on PA12 and, therefore, enables a very specific statement for the clinical use of PA12. The processing methods could have different impacts depending on the polymer.Originality/value– With the increasing application of polymers in medical devices, the mechanical properties must be ensured even after long-term clinical use. A systematic research with a realistic and still-defined cyclic stress is shown in this paper. Especially the testing of laser sintered polymers compared to injection moulded material has an important message for future patient-specific products.

In situ formation of antimicrobial silver nanoparticles and the impregnation of hydrophobic polycaprolactone matrix for antimicrobial medical device applications.

Bacterial infection associated with medical devices remains a challenge to modern medicine as more patients are being implanted with medical devices that provide surfaces and environment for bacteria colonization. In particular, bacteria are commonly found to adhere more preferably to hydrophobic materials and many of which are used to make medical devices. Bacteria are also becoming increasingly resistant to common antibiotic treatments as a result of misuse and abuse of antibiotics. There is an urgent need to find alternatives to antibiotics in the prevention and treatment of device-associated infections world-wide. Silver nanoparticles have emerged as a promising non-drug antimicrobial agent which has shown effectiveness against a wide range of both Gram-negative and Gram-positive pathogen. However, for silver nanoparticles to be clinically useful, they must be properly incorporated into medical device materials whose wetting properties could be detrimental to not only the incorporation of the hydrophilic Ag nanoparticles but also the release of active Ag ions. This study aimed at impregnating the hydrophobic polycaprolactone (PCL) polymer, which is a FDA-approved polymeric medical device material, with hydrophilic silver nanoparticles. Furthermore, a novel approach was employed to uniformly, incorporate silver nanoparticles into the PCL matrix in situ and to improve the release of Ag ions from the matrix so as to enhance antimicrobial efficacy.

A Tunable, Stable, and Bioactive MOF Catalyst for Generating a Localized Therapeutic from Endogenous Sources

The versatile chemical and physical properties of metal organic frameworks (MOFs) have made them unique platforms for the design of biomimetic catalysts, but with only limited success to date due to instability of the MOFs employed in physiological environments. Herein, the use of Cu(II)1,3,5‐Benzene‐tris‐triazole (CuBTTri) is demonstrated for the catalytic generation of the bioactive agent nitric oxide (NO) from endogenous sources, S‐nitrosothiols (RSNOs). CuBTTri exhibits structural integrity in aqueous environments, including phosphate buffered saline (76 h, pH 7.4, 37 °C), cell media used for in vitro testing (76 h, pH 7.4, 37 °C), and fresh citrated whole blood (30 min, pH 7.4, 37 °C). The application of CuBTTri for use in polymeric medical devices is explored through the formation of a composite CuBTTri‐poly by blending CuBTTri into biomedical grade polyurethane matrices. Once prepared, the CuBTTri‐poly material retains the catalytic function towards the generation of NO with tunable release kinetics proportional to the total content of CuBTTri embedded into the polymeric material with a surface flux corresponding to the therapeutic range of 1–100 nm cm−2 min−1, which is maintained even following exposure to blood.

3D 프린터를 이용한 마이크로 리액터 가공에 관한 연구

A 3D printer was used to fabricate a micro-TAS system for biomedical applications. A polymeric medical device fabrication based on a 3D printer can be performed at atmospheric conditions. A CAD- and CAM-based system is a flexible method to design medical components, and a 3D printer is a suitable device to perform this task. In this research, a 100-micron-wide fluidic channel was fabricated with a high-aspect ratio. A cross-sectional SEM image confirmed its possible usage in a micro-reactor using 3D printers. CNC-machined samples were compared to 3D printer-fabricated samples, and the advantages and disadvantages were discussed. Based on the SEM images, the surface roughness of the 3D printed reactor was not affected by wet or dry conditions due to its manufacturing principle. An aspect ratio of 5 to 1 was achievable with 100-<TEX>${\mu}$</TEX> m-wide fluid channels. No melting was found, and the shape of channels was straight enough to be used for micro reactors.

Coated melt-spun acrylonitrile-based suture for delayed release of nitric oxide

Nitric oxide (NO) plays an important role in physiological functions in the body, naturally synthesized by nitric oxide synthase. NO has been shown to enhance wound healing, generating research interest in the incorporation of NO into thromboresistant polymers for medical devices. Such polymers can be processed by melt-spinning to create surgical suture type materials. These melt-spun sutures can have the high tensile strength and durability necessary for wound closure. NO release from the suture can be controlled by application of a biodegradable coating. In this work, an acrylonitrile-co-1-vinylimidazole (AN/VIM) copolymer was melt-spun and coated with PCL. The coated suture fibers were studied for NO storage and release. Addition of a PCL coating significantly slows release of the NO compared to the uncoated AN/VIM suture. Over 24h, the coated suture released 46 (±12)µmol NO/g AN.

Highly effective antibiofilm coating of silver–polymer nanocomposite on polymeric medical devices deposited by one step plasma process

Foley's catheters were coated with Silver (Ag), plasma polymerized aniline (PPAni) and Ag-PPAni composite by plasma based deposition processes which were characterized by XRD, EDX, SEM, and FT-IR spectroscopy and bioassays were performed to validate their efficacies to kill planktonic cells as well as to remove biofilm. The analyses confirmed the formation of Ag nanoparticles (AgNPs), PPAni and Ag-PPAni composite and also corroborated their successful deposition over the catheters. Antibacterial assays showed that coated catheters were capable of killing planktonic cells of most commonly encountered uropathogens and equally capable of eradicating biofilm formation by the uropathogens as evident from the reduced cfu/ml. UV-vis spectroscopy results showed that the nanoparticle coated catheters were capable of gradual release of AgNPs, killing all planktonic cells in solution over the time. Foley's catheters coated with AgNPs and their composites by one step plasma process were non-toxic devices capable of killing planktonic cells and proficient in eradicating biofilm formation which could be used to cutback the likelihood of the catheter related complications.

Prediction and validation of diffusion coefficients in a model drug delivery system using microsecond atomistic molecular dynamics simulation and vapour sorption analysis.

Diffusion of small to medium sized molecules in polymeric medical device materials underlies a broad range of public health concerns related to unintended leaching from or uptake into implantable medical devices. However, obtaining accurate diffusion coefficients for such systems at physiological temperature represents a formidable challenge, both experimentally and computationally. While molecular dynamics simulation has been used to accurately predict the diffusion coefficients, D, of a handful of gases in various polymers, this success has not been extended to molecules larger than gases, e.g., condensable vapours, liquids, and drugs. We present atomistic molecular dynamics simulation predictions of diffusion in a model drug eluting system that represent a dramatic improvement in accuracy compared to previous simulation predictions for comparable systems. We find that, for simulations of insufficient duration, sub-diffusive dynamics can lead to dramatic over-prediction of D. We present useful metrics for monitoring the extent of sub-diffusive dynamics and explore how these metrics correlate to error in D. We also identify a relationship between diffusion and fast dynamics in our system, which may serve as a means to more rapidly predict diffusion in slowly diffusing systems. Our work provides important precedent and essential insights for utilizing atomistic molecular dynamics simulations to predict diffusion coefficients of small to medium sized molecules in condensed soft matter systems.

Optimization of Micro Injection Molding of Polymeric Medical Devices Using Software Tools

Micro injection molding is a domain which implies challenges for both producers of moulds and technologists. Due to special conditions required by the process of micro injection molding, chemical, physical and thermal properties of the injected polymeric material are affected, material behaviour is different compared with that during the classical process of injection moulding and so, optimization of parameters of the injection process is needed. This work has shown the process of optimization of micro injection in template given a medical application. A numerical analysis has been performed using the Autodesk Moldflow Insight software given a “surgical micro-stitch” marker device.

Inhibition of Microbial Growth on Chitosan Membranes by Plasma Treatment

The use of polymeric medical devices has stimulated the development of new sterilization methods. The traditional techniques rely on ethylene oxide, but there are many questions concerning the carcinogenic properties of the ethylene oxide residues adsorbed on the materials after processing. Another common technique is the gamma irradiation process, but it is costly, its safe operation requires an isolated site, and it also affects the bulk properties of the polymers. The use of gas plasma is an elegant alternative sterilization technique. The plasma promotes efficient inactivation of the microorganisms, minimizes damage to the materials, and presents very little danger for personnel and the environment. In this study we used plasma for microbial inhibition of chitosan membranes. The membranes were treated with oxygen, methane, or argon plasma for different time periods (15, 30, 45, or 60 min). For inhibition of microbial growth with oxygen plasma, the time needed was 60 min. For the methane plasma, samples were successfully treated after 30, 45, and 60 min. For argon plasma, all treatment periods were effective.

In vitro human skin irritation test for evaluation of medical device extracts

The aim of this study was to determine if the EpiDerm™ reconstructed human skin model (MatTek Corp.) could be an acceptable alternative to the ISO 10993-required rabbit skin irritation test for assessing medical device biocompatibility. Eleven medical device polymers were tested. Four extracts were prepared per polymer, two each with saline and sesame oil; half were spiked with two R-38 irritants, lactic acid for saline extracts and heptanoic acid for the sesame oil extracts. Tissue viability was assessed by MTT reduction and the proinflammatory response was assessed by IL-1α release. LOAELs of 2% for lactic acid in saline and 0.7% for heptanoic acid in sesame oil were determined. A cell viability reduction of >50% was indicative of skin irritation. Cells exposed to saline extracts spiked with 3.25% lactic acid had significantly reduced mean cell viabilities (12.6–17.2%). Cells exposed to sesame oil extracts spiked with 1.25% heptanoic acid also exhibited reduced mean cell viabilities (25.5%–41.7%). All spiked cells released substantial amounts of IL-1α (253.5–387.4pg/ml) signifying a proinflammatory response. These results indicate that the EpiDerm™ model may be a suitable in vitro replacement for the assessment of the irritation potential of medical device extracts.