Domains and Methods of Medical Device Technology Evaluation: A Systematic Review.

Objectives: Identify, through a systematic review, the main domains and methods to support health technology assessment of Medical Devices (MD) from the perspective of technological incorporation into healthcare systems. Methods: Performed structured searches in MEDLINE, Embase, BVS, Cochrane Library, and Web of Science for full studies published between 2017 and May 2023. Selection, extraction, and quality assessment were performed by two blinded reviewers, and discrepancies were resolved by a third reviewer. Results: A total of 5,790 studies were retrieved, of which 41 were included. We grouped the identified criteria into eight domains for the evaluations. Conclusion: Overall, studies discuss the need to establish specific methods for conducting HTA in MD. Due to the wide diversity of MD types, a single methodological guideline may not encompass all the specificities and intrinsic characteristics of the plurality of MD. Studies suggest using clustering criteria through technological characterization as a strategy to make the process as standardized as possible.

Evaluating the Construct Validity of the Charité Alarm Fatigue Questionnaire using Confirmatory Factor Analysis.

Background: The Charité Alarm Fatigue Questionnaire (CAFQa) is a 9-item questionnaire that aims to standardize how alarm fatigue in nurses and physicians is measured. We previously hypothesized that it has 2 correlated scales, one on the psychosomatic effects of alarm fatigue and the other on staff's coping strategies in working with alarms. Objective: We aimed to validate the hypothesized structure of the CAFQa and thus underpin the instrument's construct validity. Methods: We conducted 2 independent studies with nurses and physicians from intensive care units in Germany (study 1: n=265; study 2: n=1212). Responses to the questionnaire were analyzed using confirmatory factor analysis with the unweighted least-squares algorithm based on polychoric covariances. Convergent validity was assessed by participants' estimation of their own alarm fatigue and exposure to false alarms as a percentage. Results: In both studies, the χ2 test reached statistical significance (study 1: χ226=44.9; P=.01; study 2: χ226=92.4; P<.001). Other fit indices suggested a good model fit (in both studies: root mean square error of approximation <0.05, standardized root mean squared residual <0.08, relative noncentrality index >0.95, Tucker-Lewis index >0.95, and comparative fit index >0.995). Participants' mean scores correlated moderately with self-reported alarm fatigue (study 1: r=0.45; study 2: r=0.53) and weakly with self-perceived exposure to false alarms (study 1: r=0.3; study 2: r=0.33). Conclusions: The questionnaire measures the construct of alarm fatigue as proposed in our previous study. Researchers and clinicians can rely on the CAFQa to measure the alarm fatigue of nurses and physicians.

3D-printing inherently MRI-visible accessories in aiding MRI-guided biopsies.

BACKGROUND: 3D printers have gained prominence in rapid prototyping and viable in creating dimensionally accurate objects that are both safe within a Magnetic Resonance Imaging (MRI) environment and visible in MRI scans. A challenge when making MRI-visible objects using 3D printing is that hard plastics are invisible in standard MRI scans, while fluids are not. So typically, a hollow object will be printed and filled with a liquid that will be visible in MRI scans. This poses an engineering challenge however since objects created using traditional Fused Deposition Modeling (FDM) 3D-printing techniques are prone to leakage. Digital Light Processing (DLP) is a relatively modern and affordable 3D-printing technique using UV-hardened resin, capable of creating objects that are inherently liquid-tight. When printing hollow parts using DLP printers, one typically requires adding drainage holes for uncured liquid resin to escape during the printing process. If this is not done liquid resin will remain inside the object, which in our application is the desired outcome. PURPOSE: We devised a method to produce an inherently MRI-visible accessory using DLP technology with low dimensional tolerance to facilitate MRI-guided breast biopsies. METHODS: By hollowing out the object without adding drainage holes and tuning printing parameters such as z-lift distance to retain as much uncured liquid resin inside as possible through surface tension, objects that are inherently visible in MRI scans can be created without further post-processing treatment. RESULTS: Objects created through our method are simple and inexpensive to recreate, have minimal manufacturing steps, and are shown to be dimensionally exact and inherently MRI visible to be directly used in various applications without further treatment. CONCLUSION: Our proposed method of manufacturing objects that are inherently both MRI safe, and MRI visible. The proposed process is simple and does not require additional materials and tools beyond a DLP 3D-printer. With only an inexpensive DLP 3D-printer kit and basic cleaning and sanitation materials found in the hospital, we have demonstrated the viability of our process by successfully creating an object containing fine structures with low spatial tolerances used for MRI-guided breast biopsies.

Hospital process performance and the adoption of medical devices: An organization-based view.

Over the past two decades, there has been a growing scholarly interest in the adoption of technology in healthcare. While numerous studies have delved into the effects of specific technologies on the performance of different organizational units and medical specialties, the findings have often been divergent. Unlike the established literature, our approach focuses on the organization's perspective to analyze how technology impacts process performance in hospital settings. More precisely, we compiled a tailored dataset from 56 healthcare organizations in Italy and conducted a comprehensive analysis of panel data from 2016 to 2019, utilizing Ordinary Least Squares (OLS) regression as our main analytical tool. The data shows a clear relationship between an organization's use of medical devices and its overall process performance. Our research highlights the importance of achieving substantial improvements in process performance by strategically integrating new technologies and devices. Policymakers are encouraged to consider introducing incentives to drive hospitals to invest in innovative technologies. Furthermore, monitoring expenditures on new devices could serve as a valuable metric for assessing the extent of technology adoption within clinical practices.

Comparisons between In-Check DIAL® and PF810® in evaluation and training inspiratory capacity for using dry powder inhalers.

BACKGROUND: Dry powder inhalers (DPIs) rely on both internal resistance and patients' inspiratory capacity for effective operation. Optimal inspiratory technique is crucial for DPI users. This study assessed the accuracy and repeatability of two available devices, PF810® and In-Check DIAL®, and analyzed their measurement errors and consistency in detecting inspiratory capacity. METHODS: The accuracy and repeatability of peak inspiratory flow (PIF) and forced inspiratory vital capacity (FIVC) against various internal resistances of the two devices were assessed using standard waveforms generated by a breathing simulator. The agreement of PIF measurements between the two devices in healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was analyzed with the intraclass correlation coefficient and Bland-Altman graphical analysis. RESULTS: PF810® showed great accuracy and repeatability in measuring PIF, except for square waveforms at the lowest flow rate (20 L/min). In-Check DIAL® exhibited poor accuracy against high resistance levels. In scenarios with no resistance, In-Check DIAL® had significantly smaller measurement errors than PF810®, but larger errors against high resistance levels. The two devices showed excellent agreement (ICC > 0.80, P < 0.05), except for healthy volunteers against medium to high resistance (R3-R5) where the ICC was insignificant. Bland-Altman plots indicated small disagreements between the two devices for both healthy volunteers and COPD patients. CONCLUSIONS: In-Check DIAL® exhibited poor accuracy and larger measurement errors than PF810® when detecting PIFs against higher internal resistances. However, its good performance against lower internal resistances, along with its cost-effectiveness and convenience made it appropriate for primary care. PF810® showed good accuracy and repeatability and could detect additional parameters of inspiratory capacity beyond PIF, though required further studies to confirm its clinical benefits.

Open-source synthetic photoplethysmographic signal generator with analog output.

The photoplethysmographic (PPG) signal of the finger is being used to create embedded devices that estimate physiological variables. This project outlines an innovative method for developing a synthetic PPG generator that produces both actual reference digital signals and their equivalent analog signals using open-source technology. A series of PPG profiles is synthesized using three variant Gaussian functions. A low-frequency trend induced by respiratory frequency and background noise are then added. To generate a diverse range of continuously variable PPG profiles within specified boundaries and customizable levels of interference, all parameters undergo random fluctuations on a cycle-by-cycle basis, as per user-defined constraints. The generated signal is then converted into its equivalent analog form through the use of an RC filter that low-frequency filters a Pulse-Width Modulation square wave that is modulated directly by the generated signal. The software returns different PPG profiles and allows the signal comparison before vs after the addition of different-intensity modulated respiratory trends and background noise. The digital signal is faithfully converted into an equivalent analog voltage signal capable of reproducing not only the waveform profile but also the respiratory trend and various levels of noise.

Screening of Lithium Substituted Ag-TiO2 Nanoparticle Coating for Antibiofilm Application.

Bacterial infections and biofilm growth are common mishaps associated with medical devices, and they contribute significantly to ill health and mortality. Removal of bacterial deposition from these devices is a major challenge, resulting in an immediate necessity for developing antibacterial coatings on the surfaces of medical implants. In this context, we developed an innovative coating strategy that can operate at low temperatures (80 °C) and preserve the devices' integrity and functionality. An innovative Ag-TiO2 based coating was developed by ion exchange between silver nitrate (AgNO3) and lithium titanate (Li4Ti5O12) on glass substrates for different periods, ranging from 10 to 60 min. The differently coated samples were tested for their antibacterial and antibiofilm efficacy.

Regulatory landscape, risks, and solutions for refurbished medical devices: a comparative analysis in the US, EU, Malaysia, and Ghana.

INTRODUCTION: Refurbished medical devices are previously owned equipment that undergo a process of restoration to ensure they meet quality standards and function effectively. The utilization of refurbished medical devices, coupled with the integration of software, poses intricate challenges in terms of regulatory compliance, risk management, and patient safety. AREAS COVERED: This article explores the regulatory frameworks governing refurbished medical devices in the United States (US), the European Union (EU), Malaysia, and Ghana. Included information from a range of primary and secondary sources. Additionally, it aims to identify and analyze the risks associated with refurbished medical devices, with a specific focus on the implications of software integration, and recommend practical solutions for mitigating these risks. EXPERT OPINION: The landscape of refurbished medical devices presents challenges in terms of regulatory compliance, risk management, and patient safety. Addressing these challenges requires careful consideration and strategies to ensure that refurbished devices meet stringent quality standards. By focusing on these areas, policymakers and healthcare professionals can enhance the safe utilization of refurbished medical devices, thereby improving access to quality healthcare, particularly in underserved regions.

Using Topic Modeling to Understand Patients' and Caregivers' Perspectives About Left Ventricular Assist Device: Thematic Analysis.

BACKGROUND: Heart failure (HF) is a significant global clinical and public health challenge, impacting 64.3 million individuals worldwide. To address the scarcity of donor organs, left ventricular assist device (LVAD) implantation has become a crucial intervention for managing end-stage HF, serving as a bridge to heart transplantation or as a destination therapy. Web-based health forums, such as MyLVAD.com, play a vital role as trusted sources of information for individuals with HF symptoms and their caregivers. OBJECTIVE: We aim to uncover the latent topics within the posts shared by users on the MyLVAD.com website. METHODS: Using the latent Dirichlet allocation algorithm and a visualization tool, our objective was to uncover latent topics within the posts shared on the MyLVAD.com website. Through the application of topic modeling techniques, we analyzed 459 posts authored by recipients of LVAD and their family members from 2015 to 2023. RESULTS: This study unveiled 5 prominent themes of concern among patients with LVAD and their family members. These themes included family support (39.5% weight value), encompassing subthemes such as family caregiving roles and emotional or practical support; clothing (23.9% weight value), with subthemes related to comfort, normalcy, and functionality; infection (18.2% weight value), covering driveline infections, prevention, and care; power (12% weight value), involving challenges associated with power dependency; and self-care maintenance, monitoring, and management (6.3% weight value), which included subthemes such as blood tests, monitoring, alarms, and device management. CONCLUSIONS: These findings contribute to a better understanding of the experiences and needs of patients implanted with LVAD, providing valuable insights for health care professionals to offer tailored support and care. By using latent Dirichlet allocation to analyze posts from the MyLVAD.com forum, this study sheds light on key topics discussed by users, facilitating improved patient care and enhanced patient-provider communication.

More than red tape: exploring complexity in medical device regulatory affairs.

Introduction: This study investigates the complexity of regulatory affairs in the medical device industry, a critical factor influencing market access and patient care. Methods: Through qualitative research, we sought expert insights to understand the factors contributing to this complexity. The study involved semi-structured interviews with 28 professionals from medical device companies, specializing in various aspects of regulatory affairs. These interviews were analyzed using a mix of qualitative coding and natural language processing (NLP) techniques. Results: The findings reveal key sources of complexity within the regulatory landscape, divided into five domains: (1) regulatory language complexity, (2) intricacies within the regulatory process, (3) global-level complexities, (4) database-related considerations, and (5) product-level issues. Discussion: The participants highlighted the need for strategies to streamline regulatory compliance, enhance interactions between regulatory bodies and industry players, and develop adaptable frameworks for rapid technological advancements. Emphasizing interdisciplinary collaboration and increased transparency, the study concludes that these elements are vital for establishing coherent and effective regulatory procedures in the medical device sector.

Can mechanical heart valves perform similarly to tissue valves? An in vitro study.

Current surgical aortic valve (AV) replacement options include bioprosthetic and mechanical heart valves (MHVs), each with inherent limitations. Bioprosthetic valves offer superior hemodynamics but suffer from durability issues, typically initiating deterioration within 7-8 years. MHVs, while durable, necessitate lifelong anticoagulation therapy, presenting risks such as severe bleeding and thromboembolic events. The need for anticoagulants is caused by non-physiological flow through the hinge area during the closed phase and large spikes of regional backflow velocity (RBV) during the closing phase that produces high shear events. This study introduces the iValve, a novel MHV designed to combine the hemodynamic benefits of bioprosthetic valves with the durability of MHVs without requiring anticoagulation. The iValve features eye-like leaflets, a saddle-shaped housing, and an optimized hinge design to enhance blood flow and minimize thrombotic risk. Fabricated using 6061-T6 aluminum and polyether ether ketone (PEEK), twelve iValve iterations were evaluated for their opening and closing dynamics. The reported top-performing prototypes demonstrated competitive performance against industry standards. The proposed iValve prototype exhibited a mean RBV of -4.34 m/s with no spikes in RBV, performing similarly to bioprosthetic valves and significantly outperforming existing MHVs. The iValve's optimized design showed a 7-10% reduction in closing time and a substantial decrease in RBV spikes, potentially reducing the need for anticoagulation therapy. This study highlights the iValve's potential to revolutionize prosthetic heart valve technology by offering a durable, hemodynamically superior solution that mitigates the drawbacks of current MHVs.

AI as a Medical Device Adverse Event Reporting in Regulatory Databases: Protocol for a Systematic Review.

BACKGROUND: The reporting of adverse events (AEs) relating to medical devices is a long-standing area of concern, with suboptimal reporting due to a range of factors including a failure to recognize the association of AEs with medical devices, lack of knowledge of how to report AEs, and a general culture of nonreporting. The introduction of artificial intelligence as a medical device (AIaMD) requires a robust safety monitoring environment that recognizes both generic risks of a medical device and some of the increasingly recognized risks of AIaMD (such as algorithmic bias). There is an urgent need to understand the limitations of current AE reporting systems and explore potential mechanisms for how AEs could be detected, attributed, and reported with a view to improving the early detection of safety signals. OBJECTIVE: The systematic review outlined in this protocol aims to yield insights into the frequency and severity of AEs while characterizing the events using existing regulatory guidance. METHODS: Publicly accessible AE databases will be searched to identify AE reports for AIaMD. Scoping searches have identified 3 regulatory territories for which public access to AE reports is provided: the United States, the United Kingdom, and Australia. AEs will be included for analysis if an artificial intelligence (AI) medical device is involved. Software as a medical device without AI is not within the scope of this review. Data extraction will be conducted using a data extraction tool designed for this review and will be done independently by AUK and a second reviewer. Descriptive analysis will be conducted to identify the types of AEs being reported, and their frequency, for different types of AIaMD. AEs will be analyzed and characterized according to existing regulatory guidance. RESULTS: Scoping searches are being conducted with screening to begin in April 2024. Data extraction and synthesis will commence in May 2024, with planned completion by August 2024. The review will highlight the types of AEs being reported for different types of AI medical devices and where the gaps are. It is anticipated that there will be particularly low rates of reporting for indirect harms associated with AIaMD. CONCLUSIONS: To our knowledge, this will be the first systematic review of 3 different regulatory sources reporting AEs associated with AIaMD. The review will focus on real-world evidence, which brings certain limitations, compounded by the opacity of regulatory databases generally. The review will outline the characteristics and frequency of AEs reported for AIaMD and help regulators and policy makers to continue developing robust safety monitoring processes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/48156.

Point-of-care testing preferences 2020-2022: Trends over the years.

Background: The use of point-of-care (POC) tests prior to the COVID-19 pandemic was relatively infrequent outside of the health care context. Little is known about how public opinions regarding POC tests have changed during the pandemic. Methods: We redeployed a validated survey to uncompensated volunteers to assess preferences for point-of-care testing (POCT) benefits and concerns between June and September 2022. We received a total of 292 completed surveys. Linear regression analysis was used to compare differences in survey average response scores (ARSs) from 2020 to 2022. Results: Respondent ARSs indicated agreement for all 16 POCT benefits in 2022. Of 14 POCT concerns, there were only 2 statements that respondents agreed with most frequently, which were that "Insurance might not cover the costs of the POC test" (ARS 0.9, ± 1.0) and "POC tests might not provide a definitive result" (ARS 0.1, ± 1.0). Additionally, when comparing survey responses from 2020 to 2022, we observed 8 significant trends for POCT harms and benefits. Conclusion: The public's opinion on POC tests has become more favorable over time. However, concerns regarding the affordability and reliability of POCT results persist. We suggest that stakeholders address these concerns by developing accurate POC tests that continue to improve care and facilitate access to health care for all.

A Comprehensive Framework for Evaluating the Value Created by Real-World Evidence for Diverse Stakeholders: The Case for Coordinated Registry Networks.

OBJECTIVES: This manuscript presents a comprehensive framework for the assessment of the value of real-world evidence (RWE) in healthcare decision-making. While RWE has been proposed to overcome some limitations of traditional, one-off studies, no systematic framework exists to measure if RWE actually lowers the burden. This framework aims to fill that gap by providing conceptual approaches for evaluating the time and cost efficiencies of RWE, thus guiding strategic investments in RWE infrastructure. METHODS: The framework consists of four components: (114th Congress. 21st Century Cures Act.; 2015. https://www.congress.gov/114/plaws/publ255/PLAW-114publ255.pdf .) identification of stakeholders using and producing RWE, (National Health Council. Glossary of Patient Engagement Terms. Published 2019. Accessed May 18. 2021. https://nationalhealthcouncil.org/glossary-of-patient-engagement-terms/ .) understanding value propositions on how RWE can benefit stakeholders, (Center for Drug Evaluation and Research. CDER Patient-Focused Drug Development. U.S. Food & Drug Administration.) defining key performance indicators (KPIs), and (U.S. Department of Health and Human Services - Food and Drug Administration: Center for Devices and Radiological Health and Center for Biologics Evaluation and Research. Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices - Guidance for Industry and Food and Drug Administration Staff. 2017. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guida .) establishing metrics and case studies to assess value. KPIs are categorized as 'better, faster, or cheaper" as an indicator of value: better focusing on high-quality actionable evidence; 'faster,' denoting time-saving in evidence generation, and 'cheaper,' emphasizing cost-efficiency decision compared to methodologies that do not involve data routinely collected in clinical practice. Metrics and relevant case studies are tailored based on stakeholder value propositions and selected KPIs that can be used to assess what value has been created by using RWE compared to traditional evidence-generation approaches and comparing different RWE sources. RESULTS: Operationalized through metrics and case studies drawn from the literature, the value of RWE is documented as improving treatment effect heterogeneity evaluation, expanding medical product labels, and expediting post-market compliance. RWE is also shown to reduce the cost and time required to produce evidence compared to traditional one-off approaches. An original example of a metric that measures the time saved by RWE methods to detect a signal of a product failure was presented based on analysis of the National Cardiovascular Disease Registry. CONCLUSIONS: The framework presented in this manuscript offers a comprehensive approach for evaluating the value of RWE, applicable to all stakeholders engaged in leveraging RWE for healthcare decision-making. Through the proposed metrics and illustrated case studies, valuable insights are provided into the heightened efficiency, cost-effectiveness, and improved decision-making within clinical and regulatory domains facilitated by RWE. While this framework is primarily focused on medical devices, it could potentially inform the determination of RWE value in other medical products. By discerning the variations in cost, time, and data utility among various evidence-generation methods, stakeholders are empowered to invest strategically in RWE infrastructure and shape future research endeavors.

Systematic review on the implementation of metrological assurance systems for medical devices in Latin America.

Background: Metrology plays a crucial role in small healthcare service businesses to ensure the quality of products and services. While legal metrology in healthcare exists in some regions, it lacks harmonization. In other countries, there is limited presence of metrology in medical and biomedical engineering. We aimed to evaluate the implementation of metrological assurance systems for medical devices in Latin America. Methods: A systematic review was conducted following PRISMA 2020 guidelines and registered with PROSPERO (CRD42022359284). Searches were performed across 13 databases from October 30th to November 3rd, 2022. The search equation was "(((quality assurance) AND (metrology)) AND (medical devices))." A total of 7,789 documents were identified, of which only 16 met the inclusion criteria. Results: The majority of studies (75%) were conducted in Colombia, with a significant portion being undergraduate theses. The primary normative references used in the analyzed studies were ISO 10012 and ISO 17025, with the majority (68.75%) relying on national legislation for their approach. One study in Colombia referenced eight standards, and one in Brazil analyzed user involvement in medical device management. Among the included studies, 56.25% were conducted in healthcare institutions, mainly clinics. Most studies provided implementation guidelines, with ISO 10012 being prominent, alongside ISO 17025, which implicitly addresses ISO 9001 elements. Global bias was low across all studies. Conclusion: Our results underscore the importance of metrological assurance in managing medical devices in Latin America. The utilization of international standards and national legislation illustrates the diverse approaches adopted by different institutions. Future research should focus on optimizing metrological practices to enhance quality and safety in healthcare.

Teaching Medical Devices through Interactive Innovation: Challenges and Rewards.

Medical devices are manmade objects existing at the interface between numerous disciplines. They range from as simple as medical gloves to as complex as artificial limbs. This versatility of medical devices and their inherent interdisciplinary nature means that academic courses on them are attended by cohorts of students from varieties of academic backgrounds, who bring with them similarly broad spectra of interests. To satisfy the learning expectations of each and every student in such diverse classes is a daunting task for the instructor. After many years of teaching medical devices at undergraduate and graduate levels at three different universities in the states of Illinois and California, I have come up with an instructional method that solves this challenge by engaging students in the co-creation of the curriculum via selection of their own medical devices of interest and presentation to the class for collective analysis. The threefold presentations are designed so that they reflect an ascent along the hierarchy of a learning taxonomy extending from foundational concepts to critical assessment of knowledge to creative displays of it. In such a way, the students are acquainted with the ability of critical and creative thinking at the expense of rote memorization or inculcation and are prepared to enter the field of medical devices as innovation-centered individuals. The specifics of this new method of instruction are reported here, with the hope that they will be useful to fellow instructors in any interdisciplinary course that benefits from a balance between the rigorous coverage of the instructional material pertaining to engineering and medicine and the flexible selection of topics that comply with students' individual interests.

Effects of wearable low-intensity continuous ultrasound on muscle biomechanical properties during delayed onset muscle soreness.

BACKGROUND: Delayed onset muscle soreness (DOMS) is one of the most prevalent musculoskeletal symptoms in individuals engaged in strenuous exercise programs. OBJECTIVE: This study investigated the effects of wearable low-intensity continuous ultrasound on muscle biomechanical properties during DOMS. METHODS: Twenty volunteers were distributed into a wearable ultrasound stimulation group (WUG) (n= 10) and medical ultrasound stimulation group (MUG) (n= 10). All subjects performed wrist extensor muscle strength exercises to induce DOMS. At the site of pain, ultrasound of frequency 3 MHz was applied for 1 h or 5 min in each subject of the WUG or MUG, respectively. Before and after ultrasound stimulation, muscle biomechanical properties (tone, stiffness, elasticity, stress relaxation time, and creep) and body temperature were measured, and pain was evaluated. RESULTS: A significant decrease was found in the tone, stiffness, stress relaxation time, and creep in both groups after ultrasound stimulation (all p< 0.05). A significant decrease in the pain and increases in temperature were observed in both groups (all p< 0.05). No significant differences were observed between the groups in most evaluations. CONCLUSION: The stiffness and pain caused by DOMS were alleviated using a wearable ultrasound stimulator. Furthermore, the effects of the wearable ultrasound stimulator were like those of a medical ultrasound stimulator.

Targeting Macrophage Polarization for Reinstating Homeostasis following Tissue Damage.

Tissue regeneration and remodeling involve many complex stages. Macrophages are critical in maintaining micro-environmental homeostasis by regulating inflammation and orchestrating wound healing. They display high plasticity in response to various stimuli, showing a spectrum of functional phenotypes that vary from M1 (pro-inflammatory) to M2 (anti-inflammatory) macrophages. While transient inflammation is an essential trigger for tissue healing following an injury, sustained inflammation (e.g., in foreign body response to implants, diabetes or inflammatory diseases) can hinder tissue healing and cause tissue damage. Modulating macrophage polarization has emerged as an effective strategy for enhancing immune-mediated tissue regeneration and promoting better integration of implantable materials in the host. This article provides an overview of macrophages' functional properties followed by discussing different strategies for modulating macrophage polarization. Advances in the use of synthetic and natural biomaterials to fabricate immune-modulatory materials are highlighted. This reveals that the development and clinical application of more effective immunomodulatory systems targeting macrophage polarization under pathological conditions will be driven by a detailed understanding of the factors that regulate macrophage polarization and biological function in order to optimize existing methods and generate novel strategies to control cell phenotype.

Regulating AI-Based Medical Devices in Saudi Arabia: New Legal Paradigms in an Evolving Global Legal Order.

This paper examines the Saudi Food and Drug Authority's (SFDA) Guidance on Artificial Intelligence (AI) and Machine Learning (ML) technologies based Medical Devices (the MDS-G010). The SFDA has pioneered binding requirements designed for manufacturers to obtain Medical Device Marketing Authorization. The regulation of AI in health is at an early stage worldwide. Therefore, it is critical to examine the scope and nature of the MDS-G010, its influences, and its future directions. It is argued that the guidance is a patchwork of existing international best practices concerning AI regulation, incorporates adapted forms of non-AI-based guidelines, and builds on existing legal requirements in the SFDA's existing regulatory architecture. There is particular congruence with the approaches of the US Food and Drug Administration (FDA) and the International Medical Device Regulators Forum (IMDRF), but the SFDA goes beyond those approaches to incorporate other best practices into its guidance. Additionally, the binding nature of the MDS-G010 is complex. There are binding 'components' within the guidance, but the incorporation of non-binding international best practices which are subordinate to national law results in a lack of clarity about how penalties for non-compliance will operate.

Unveiling, Analyzing the Mechanisms of, and Proposing Solutions for Bribery in Japan's Medical Device Sector.

Both public and academic scrutiny of the financial relationships between the medical device industry and the healthcare society occur less frequently than those involving the pharmaceutical industry, and Japan is no exception to these shortcomings. This paper examines the ethical and legal challenges inherent in Japan's medical device industry through the lens of bribery scandals, placing these issues within the broader context of global healthcare corruption. It aims to derive lessons and suggest universal strategies for ethical and legal enhancements. The discussion includes two notable cases: one involving inappropriate transactions between a cancer center and a biliary stent manufacturer, and another concerning a corrupt donation scheme between a medical device company and a university's anesthesiology department, which was found guilty. In our analysis, we also acknowledge the industry's efforts toward compliance and reform to maintain a balanced perspective. The analysis not only highlights the unique culture and structure of the Japanese medical device industry, such as the exploitation of flexible pricing and opaque financial practices but also contrasts these issues with the tightly regulated pharmaceutical industry. This approach reveals both sector-specific challenges and common corruption drivers, enhancing our understanding of why such scandals occur and persist. We propose ethical and compliance-focused business measures such as centralizing donation decisions, limiting the financial independence of marketing divisions, and increasing transparency, alongside adopting mandatory disclosure practices based on successful models from the United States and Europe. By emphasizing integrity and presenting diverse perspectives, this study aims to elevate ethical and legal standards in the medical device industry and improve patient health outcomes worldwide.