Failure Of Medical Devices Research Articles

Evaluation of the Influence of Pharmaceuticals on the Mechanical Properties of Polymeric Medical Devices

Pharmaceuticals reportedly cause damage to some polymeric medical devices that administer them. Because this phenomenon and its causes still remain unclear, in this study, all the possible combinations of polymeric materials and pharmaceutical ingredients that could cause failures were identified by conducting a comprehensive analysis on a wide variety of such combinations and through verification tests using the products. The results of the simple immersion tests and the reports of clinical failures indicated that the failures were not caused by the lack of chemical resistance of the polymers but by the environmental stress cracking (ESC) induced by a combination of the stress generated in the material and the interaction with a specific chemical. Therefore, we evaluated all combinations that could cause ESC by developing and applying a simple method for testing ESC. Polycarbonate and polyethylene terephthalate were found to be damaged by alkaline solutions and oils and fats, and surfactants solutions. These failures were also confirmed by the verification tests. Results from the stress state verification, fractographic analysis, and other studies confirmed that these failures were caused by ESC. Cytotoxicity owing to the induction of ESC was not detected in any combination. These results indicated that the residual stress generated during the manufacturing process was one of the reasons for the failure of the medical devices. This residual stress can be eliminated by employing additional processes such as annealing, thereby preventing medical device failures induced through interactions with pharmaceutical ingredients.

Blood-Compatible Materials: Vascular Endothelium-Mimetic Surfaces that Mitigate Multiple Cell-Material Interactions.

When flowing whole blood contacts medical device surfaces, the most common blood-material interactions result in coagulation, inflammation, and infection. Many new blood-contacting biomaterials have been proposed based on strategies that address just one of these common modes of failure. This study proposes to mitigate unfavorable biological reactions that occur with blood-contacting medical devices by designing multifunctional surfaces, with features optimized to meet multiple performance criteria. These multifunctional surfaces incorporate the release of the small molecule hormone nitric oxide (NO) with surface chemistry and nanotopography that mimic features of the vascular endothelial glycocalyx. These multifunctional surfaces have features that interact with coagulation components, inflammatory cells, and bacterial cells. While a single surface feature alone may not be sufficient to achieve multiple functions, the release of NO from the surfaces along with their modification to mimic the endothelial glycocalyx synergistically improves platelet-, leukocyte-, and bacteria-surface interactions. This work demonstrates that new blood-compatible materials should be designed with multiple features, to better address the multiple modes of failure of blood-contacting medical devices.

Investigating the stress corrosion cracking of a biodegradable Zn-0.8 wt%Li alloy in simulated body fluid

Stress corrosion cracking (SCC) may lead to brittle, unexpected failure of medical devices. However, available researches are limited to Mg-based biodegradable metals (BM) and pure Zn. The stress corrosion behaviors of newly-developed Zn alloys remain unclear. In the present work, we conducted slow strain rate testing (SSRT) and constant-load immersion test on a promising Zn-0.8 wt%Li alloy in order to investigate its SCC susceptibility and examine its feasibility as BM with pure Zn as control group. We observed that Zn-0.8 wt%Li alloy exhibited low SCC susceptibility. This was attributed to variations in microstructure and deformation mechanism after alloying with Li. In addition, both pure Zn and Zn-0.8 wt%Li alloy did not fracture over a period of 28 days during constant-load immersion test. The magnitude of applied stress was close to physiological condition and thus, we proved the feasibility of both materials as BM.

Is your healthcare organisation using sound quality assurance principles? Part 2: coping with the unexpected

This is the second article in a two-part series that proposes how healthcare organisations could implement a quality assurance approach based on the requirements of a thus far unwritten healthcare modification of the 2015 International Organization for Standardization (ISO 9001). This second article will address the issue of unexpected failures of manufactured medical implants and medication delivery devices. Issues facing the quality assured supply of medical equipment, as well as the failure of implants during fitting or use and the failure or malfunction of powered syringes or drips, is discussed. At the end of the article, a list of self-audit questions is proposed to allow readers to make an assessment of how their own organisation has responded to the failure of medical implants or devices in the past, and whether action has been taken to prevent any problems reoccurring.

Design and Implementation of Remote Firmware Update System Based on IAP Technology

This paper introduces a network remote firmware update system based on IAP technology, which aims to solve the problems of low efficiency and high cost in the traditional upgraded medical device firmware (lower computer program) mode, and to improve the portability of the lower computer program upgrade maintenance. In order to better cope with market changes, customer needs, and solve software failures in medical devices, it is necessary to update and upgrade medical device software in a timely manner. Through the IAP technology and Internet communication technology of STM32 platform, this solution can complete the update of all instrument firmware in a short time, which not only saves a lot of travel expenses, mailing costs and labor costs, but also greatly shortens the update time.

In-situ crosslinked wet spun collagen triple helices with nanoscale-regulated ciprofloxacin release capability

The design of antibacterial-releasing coatings or wrapping materials with controlled drug release capability is a promising strategy to minimise risks of infection and medical device failure in vivo. Collagen fibres have been employed as medical device building block, although they still fail to display controlled release capability, competitive wet-state mechanical properties, and retained triple helix organisation. We investigated this challenge by pursuing a multiscale design approach integrating drug encapsulation, in-situ covalent crosslinking and fibre spinning. By selecting ciprofloxacin (Cip) as a typical antibacterial drug, wet spinning was selected as a triple helix-friendly route towards Cip-encapsulated collagen fibres; whilst in situ crosslinking of fibre-forming triple helices with 1,3 phenylenediacetic acid (Ph) was hypothesised to yield Ph-Cip {\pi}-{\pi} stacking aromatic interactions and enable controlled drug release. Higher tensile modulus and strength were measured in Ph crosslinked fibres compared to state-of-the-art carbodiimide crosslinked controls. Cip-encapsulated Ph-crosslinked fibres revealed decreased elongation at break and significantly-enhanced drug retention in vitro with respect to Cip-free variants and carbodiimide-crosslinked controls, respectively. This multiscale manufacturing strategy provides new insight aiming at wet spun collagen triple helices with nanoscale-regulated tensile properties and drug release capability.

Eluted 25-hydroxyvitamin D3 from radially aligned nanofiber scaffolds enhances cathelicidin production while reducing inflammatory response in human immune system-engrafted mice

Vitamin D3 modulates immune response, induces endogenous antimicrobial peptide production, and enhances innate immunity to defend against infections. These findings suggest that incorporating vitamin D3 into medical devices or scaffolds could positively modulate host immune response and prevent infections. In the current study, we evaluated host responses and endogenous antimicrobial peptide production using 25-hydroxyvitamin D3 (25(OH)D3)-eluting radially aligned PCL nanofiber scaffolds in human immune system-engrafted mice. We transformed traditional 2D electrospun nanofiber membranes into radially aligned PCL nanofiber scaffolds using the concept of solid of revolution and an innovative gas-foaming technique. Such scaffolds can promote rapid cellular infiltration and neovascularization. The infiltrating immune cells within subcutaneously implanted 25(OH)D3-containing scaffolds mainly consisted of human macrophages in the M1 phase (CCR7+), mice macrophages in the M2 phase (CD206+), and human cytotoxic T cells (CD8+) other than few human T-helper cells (CD4+). The 25(OH)D3-eluting nanofiber scaffolds significantly inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6), while accelerating the production of anti-inflammatory cytokines (IL-4, IL-10) within the scaffolds. Additionally, we observed increased expression of human cathelicidin LL-37 within the 25(OH)D3-eluting scaffolds, while no LL-37 expression was observed in the control. Together, these findings support further work in the design of vitamin D3-eluting medical devices or scaffolds for modulating immune response and promoting antimicrobial peptide production. This could potentially reduce the inflammatory response, prevent infections, and eventually improve success rates of implants. Statement of SignificanceTransplant failure of medical devices, grafts, scaffolds, and tissue-engineered constructs due to inflammation and infection causes not only economic losses but also sufferings of second operation to the patient. Positive modulation of the host response to implants, scaffolds, and tissue-engineered constructs is likely to reduce the failure rate. Vitamin D3 plays an important role in modulating the immune response. It is able to not only reduce inflammation and induce endogenous antimicrobial peptide production but also prevent multidrug resistance and other side effects of traditional antibiotics. In this study, host responses to 25-hydroxyvitamin D3 (25(OH)D3)-eluting radially aligned PCL nanofiber scaffolds were evaluated in human immune system-engrafted mice. The 25(OH)D3-eluting medical devices or scaffolds were able to modulate positive immune response and promote antimicrobial peptide production. This work presented an innate immunity-enhancing approach for reducing the inflammatory response and preventing infections, likely resulting in improvement of success rates of implants.

A system safety approach for tomographic treatment

In recent years, technology in the medical industry has been advancing to provide safe and systematic medical care. However, medical technologies and treatments have also become more complicated, presenting new challenges for the traditional approaches used to engineer safety-critical systems. This research compares one of the most popular approaches in the medical device industry, Failure Mode and Effect Analysis (FMEA), with a relatively new method, System-Theoretic Process Analysis (STPA), in the context of a tomographic treatment system. STPA is found to be an effective means to ensure the quality of TomoTherapy and to conduct a holistic hazard analysis including both human and technical factors. A comparison of STPA and FMEA results found that STPA can identify a larger set of causal scenarios. The interactions of humans, hardware, and software were highlighted through the new STPA approach.

An exploratory analysis of U.S. FDA Class I medical device recalls: 2014–2018

Medical device manufacturing and distribution is globalised; consequently, medical device failures pose serious but preventable global public health hazard. Moreover, a clear understanding of recalls will help firms improve their operations. This study examines 871 U.S. FDA Class I (i.e. most serious) medical device recalls, highlights the shortcomings of the recall reporting system and proposes recommendations for improvement. Top three recall reasons are: “packaging” (47.4%), “component” issues (14%) and “design” (13.3%). About 40% of recall events have mischaracterised or ambiguous “FDA Determined Cause”. Ninety-four firms are related to the recalls and the majority (78%) of the recall events emanate from U.S.-headquartered firms. Thirty-four firms (36%) have been acquired or are a subsidiary of another. Results also yield recommendations for improvement. The cause classification scheme needs revision and there might be a case for more than one classification scheme. Specifically, the “device design” cause designation is conflated with “component quality” issues. “Other”, “unknown” and “under investigation” designations should be replaced with real cause determinations. The effectiveness of “Good Manufacturing Practices (GMP)” and the impact of mergers and acquisitions (M&A) on device quality should be examined. Devising a “recall severity measure” and improving and standardising the recalls database are other important issues. Results and recommendations may hold lessons for other jurisdictions as well.

Failure Mechanisms of Polymeric Medical Devices

Medical devices manufactured today typically require a number of different components and materials. Commonly, mass-produced devices utilize biocompatible polymers for their external surfaces. In this article, we discuss common failure mechanisms of polymers and a number of contributing factors, related to both the use and manufacturing of these devices. Reprocessing and cleaning of reusable medical devices can also contribute to their failures when incompatible substances or techniques are used. Thorough postmarket reporting of any medical device failure can allow enhancements of the device to be made and will ultimately improve patient safety.

Polymicrobial antibiofilm activity of the membranotropic peptide gH625 and its analogue

This work illustrates a new role for the membranotropic peptide gH625 and its derivative gH625-GCGKKK in impairing formation of polymicrobial biofilms. Mixed biofilms composed of Candida and bacterial species cause frequently infections and failure of medical silicone devices and also show a major drug resistance than single-species biofilms. Inhibition and eradication of biofilms were evaluated by complementary methods: XTT-reduction, and crystal violet staining (CV). Our results indicate that gH625-GCGKKKK, better than the native peptide, strongly inhibited formation of mixed biofilms of clinical isolates of C. tropicalis/S. marcescens and C. tropicalis/S. aureus and reduced the biofilm architecture, interfering with cell adhesion and polymeric matrix, as well as eradicated the long-term polymicrobial biofilms on silicone surface.

Nanostructured Surfaces That Mimic the Vascular Endothelial Glycocalyx Reduce Blood Protein Adsorption and Prevent Fibrin Network Formation.

Blood-contacting materials are critical in many applications where long-term performance is desired. However, there are currently no engineered materials used in cardiovascular implants and devices that completely prevent clotting when in long-term contact with whole blood. The most common approach to developing next-generation blood-compatible materials is to design surface chemistries and structures that reduce or eliminate protein adsorption to prevent blood clotting. This work proposes a new paradigm for controlling protein-surface interactions by strategically mimicking key features of the glycocalyx lining the interior surfaces of blood vessels: negatively charged glycosaminoglycans organized into a polymer brush with nanoscale domains. The interactions of two important proteins from blood (albumin and fibrinogen) with these new glycocalyx mimics are revealed in detail using surface plasmon resonance and single-molecule microscopy. Surface plasmon resonance shows that these blood proteins interact reversibly with the glycocalyx mimics, but have no irreversible adsorption above the limit of detection. Single-molecule microscopy is used to compare albumin and fibrinogen interactions on surfaces with and without glycocalyx-mimetic nanostructures. Microscopy videos reveal a new mechanism whereby the glycocalyx-mimetic nanostructures eliminate the formation of fibrin networks on the surfaces. This approach shows for the first time that the nanoscale structure and organization of glycosaminoglycans in the glycocalyx are essential to (i) reduce protein adsorption, (ii) reversibly bind fibrin(ogen), and (iii) inhibit fibrin network formation on surfaces. The insights gained from this work suggest new design principles for blood-compatible surfaces. New surfaces developed using these design principles could reduce risk of catastrophic failures of blood-contacting medical devices.

Surface immobilization of heparin and chitosan on titanium to improve hemocompatibility and antibacterial activities.

Biomaterial-related thrombus formation and bacterial infections are still the most common causes for the failure of medical devices. We report a facile and a highly efficient strategy to inhibit thrombosis and bacteria attachment, by immobilizing heparin (HA) and chitosan (CS) on titanium (Ti). Alkali-treatment was firstly performed on Ti to form nanoporous network structures containing hydroxyl radical (-OH), followed by immobilizing HA and CS on alkali-treated Ti in turn by layer-by-layer assembly. HA was immobilized on alkali-treated surface by covalent immobilization and CS was immobilized on heparinized surface by electrostatic bonding. The successful immobilization of both HA and CS on Ti was confirmed by analyses of scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and water contact angles. The antithrombotic activities of the immobilized surfaces were demonstrated by a reduction in protein absorption, blood clot mass and platelet adhesion. Additionally, the immobilized surfaces also exhibited excellent antibacterial activities against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The modified surfaces on Ti was established as an effective and promising method to simultaneous improve the hemocompatibility and antibacterial performances of blood contact medical device.

Malfunctions of Medical Devices Due to Electrostatic Occurrences Big Data Analysis of 10 Years of the FDA’s Reports

An electrostatic discharge (ESD) event can cause a medical device to fail and pose a threat to patients’safety. This paper presents the data mining analysis of ESD failures in medical devices, over the last ten years, using the U.S. FDA’s manufacturer and user facility device experience database. The most frequent failure modes and activities resulting in ESD events were identified and correlated with key environmental factors. Recommendations are then presented to medical device manufacturers and hospitals.

Intrinsic Interactions of Human Bones Loaded during Daily Activities

Standard specifications for orthopedic devices that are implanted in the human body include requirements for materials, finishing, marking, care and handling, but do not address the mechanical properties required for each type of implant. Insufficient mechanical strength is the cause of failure of medical devices. For the development of any implantable device, manufacturers demand information about the load to which the device will be subjected. In the case of fracture fixation, information is often missing. This review presents relevant information regarding biomechanics and common loads, moments and stress related to the intrinsic relation between human bones during daily activities. Results that arose from these calculations are expected to be stood by medical devices when outlined for stabilization of bone fractures

Comprehensive investigation of pharmaceutical components causing failure of medical devices made of polymers

Comprehensive investigation of pharmaceutical components causing failure of medical devices made of polymers

Theory and Application of J Charts for Holistic Risk Based Statistical Adverse Event Trending

The author attempts to postulate a new volumetric complaints and adverse events trending method for holistic risk based statistical trending using a new control chart which is based on the theory of a U chart, as it pertains to medical device failure related adverse events. Mathematical rationale is provided for various control chart parameters like subgroup size and subgroup frequency and correlations to existing literature have been made to justify conclusions. Also, the article features discussion on false alarms and how to use Minitab to minimize them while monitoring incoming complaint variability using a U chart and consequently, the J chart.

Real-time scheduling optimization considering the unexpected events in home health care

Home health care, a new kind of health services that can be given in home for special populations (elderly, disabled, youth, etc.), is usually less expensive, more convenient and more efficient. Based on the face-to-face (in-person) interviews, we find that scheduling arrangements of home health care are often affected by some unexpected events such as cancellation of services, demand for emergency care and medical device failures. These events may lead to medical scheduling conflicts and therefore might decrease patient satisfaction due to the delayed service. Considering the emergencies in the home health care, this study takes the home health care mode under the unexpected events as the research object and focuses on the time window constraints involved in the real-time scheduling problem. In order to obtain an optimal medical dispatch program and ensure patients’ golden period for treatment, we establish an effective real-time scheduling model to minimize the total required time of scheduling, and propose an improved memetic algorithm to optimize the model. Empirical analysis was then adopted to verify the rationality of the model. Finally, we analyze the practical effect of dispatching decision and put forward the recommendations for future research directions.

Inhibition activity of Lactobacilli supernatant against fungal-bacterial multispecies biofilms on silicone

Fungal-bacterial multispecies biofilms play a major role in failure of medical silicone devices, such as voice prostheses in laryngectomiy. In this study, we determined the effect of Lactobacilli supernatant (cell free) on mixed biofilm formation of fungi and bacteria on silicone in vitro. Lactobacilli supernatant inhibited the adhesion (90 min) of mixed fungi and bacteria species with an efficiency of >90%. Mixed biofilm formation and the metabolic activity of the biofilms were inhibited by 72.23% and 58.36% by Lactobacilli supernatant. The examination using confocal laser scanning microscopy and scanning electron microscopy confirmed that Lactobacilli supernatant inhibited the growth of mixed biofilm and damaged the cells. Moreover, Lactobacilli supernatant also inhibited Candida yeast–to-hyphal transition. Therefore, Lactobacilli supernatant may serve as a possible antibiofilm agent to limit biofilm formation on voice prostheses.

Evaluation of culture conditions for mixed biofilm formation with clinically isolated non-albicans Candida species and Staphylococcus epidermidis on silicone

Silicone is frequently used in clinical and medical fields for medical devices. Mixed biofilms composed of Candida and bacterial species causes frequently failure of medical silicone devices, In this in vitro study, we analyzed mixed biofilm formation of clinically isolated non-albicans Candida species and Staphylococcus epidermidis, including Candida tropicalis, Candida krusei and Candida parapsilosis under the influence of different growth media (RPMI 1640, BHI and TSB) and several culture variables (incubation period, feeding conditions and FBS). Our results showed that culture conditions strongly influence mixed biofilm formation. TSB and BHI resulted in larger amount of biofilm formations with stronger metabolic activity of biofilms. Growth conditions may also influence the biofilm formation, which was enhanced by longer incubation period, using a fed-batch system and FBS. Therefore, the potential influences of external environmental factors are very important for mixed biofilm formation with clinically isolated non-albicans Candida species and S. epidermidis, which should be considered when designing or studying the mixed biofilm under in vitro conditions.