Development Of Medical Devices Research Articles

Investigating hybrid nanoparticles for drug delivery in multi-stenosed catheterized arteries under magnetic field effects

This groundbreaking study pioneers the exploration of the therapeutic implications of a constant magnetic field simultaneously with hybrid nanoparticles on blood flow within a tapered artery, characterized by multiple stenosis along its exterior walls and a central thrombus, employing three-dimensional bio-fluid simulations. In addition, a magnetized catheter is inserted into the thrombus to increase the therapeutic potential of this novel method. The flow condition under consideration has applications in targeted medication distribution, improved medical device design, and improved diagnostics, as well as in advancing healthcare and biomedical engineering. Our investigation primarily aims to optimize blood flow efficiency, encompassing key parameters like pressure, velocity, and heat fluctuations influenced by diverse geometric constraints within the stenotic artery. Precise solutions are obtained through the finite element method (FEM) coupled with advanced bio-fluid dynamics (BFD) software. Hybrid nanoparticles and magnetic fields impacted pressure and velocity, notably reducing pressure within the stenosis. Convective heat flux remained uniform, while temperature profiles showed consistent inlet rise and gradual decline with transient variations. This approach promotes fluid flow, and convection within stenosed arteries, enhances heat transport, evacuates heat from stenotic regions, and improves heat dispersion to surrounding tissues. These findings hold promise for targeted therapies, benefiting patients with vascular disorders, and advancing our understanding of complex bio-fluid dynamics.

PBF-LB fabrication of microgrooves for induction of osteogenic differentiation of human mesenchymal stem cells

Stem cell differentiation has important implications for biomedical device design and tissue engineering. Recently, inherent material properties, including surface chemistry, stiffness, and topography, have been found to influence stem cell fate. Among these, surface topography is a key regulator of stem cells in contact with materials. The most important aspect of ideal bone tissue engineering is to control the organization of the bone extracellular matrix with fully differentiated osteoblasts. Here, we found that laser powder bed fusion (PBF-LB)-fabricated grooved surface inspired by the microstructure of bone, which induced human mesenchymal stem cell (hMSC) differentiation into the osteogenic lineage without any differentiation supplements. The periodic grooved structure was fabricated by PBF-LB which induced cell elongation facilitated by cytoskeletal tension along the grooves. This resulted in the upregulation of osteogenesis via Runx2 expression. The aligned hMSCs successfully differentiated into osteoblasts and further organized the bone mimetic-oriented extracellular matrix microstructure. Our results indicate that metal additive manufacturing technology has a great advantage in controlling stem cell fate into the osteogenic lineage, and in the construction of bone-mimetic microstructural organization. Our findings on material-induced stem cell differentiation under standard cell culture conditions open new avenues for the development of medical devices that realize the desired tissue regeneration mediated by regulated stem cell functions.

AI in imaging: the regulatory landscape.

Artificial intelligence (AI) methods have been applied to medical imaging for several decades, but in the last few years, the number of publications and the number of AI-enabled medical devices coming on the market have significantly increased. While some AI-enabled approaches are proving very valuable, systematic reviews of the AI imaging field identify significant weaknesses in a significant proportion of the literature. Medical device regulators have recently become more proactive in publishing guidance documents and recognizing standards that will require that the development and validation of AI-enabled medical devices need to be more rigorous than required for tradition "rule-based" software. In particular, developers are required to better identify and mitigate risks (such as bias) that arise in AI-enabled devices, and to ensure that the devices are validated in a realistic clinical setting to ensure their output is clinically meaningful. While this evolving regulatory landscape will mean that device developers will take longer to bring novel AI-based medical imaging devices to market, such additional rigour is necessary to address existing weaknesses in the field and ensure that patients and healthcare professionals can trust AI-enabled devices. There would also be benefits in the academic community taking into account this regulatory framework, to improve the quality of the literature and make it easier for academically developed AI tools to make the transition to medical devices that impact healthcare.

Stretchable, flexible, and breathable MXene/dopamine/thermoplastic polyurethane nanofiber membrane with outstanding strain sensing and electromagnetic interference shielding performances

Outstanding strain sensing and electromagnetic interference (EMI) shielding performances are two important indicators for high-performance nanofiber membrane in flexible wearable electronic device. Here, simple electrospinning was employed to prepare the nanofiber membrane of thermoplastic polyurethane (TPU) as substrate. Then high-performance nanofiber membrane was developed by synthesizing dopamine on TPU nanofibers to form poly-dopamine (PDA) coatings (named PT) and ultrasonically loading MXene on PT (labeled MPT). Specifically, TPU substrate provides flexibility and breathability, PDA coating improves the adhesion between MXene and TPU, and MXene contributes to strain sensing and EMI shielding performances. Owing to the PDA coatings, MPT nanofiber membrane has outstanding EMI shielding efficiency (EMI SE) of 69.86 dB at 150 μm thickness and an absolute effective shielding value of 8383.33 dBcm2g−1. The combination of PDA with MXene improves the EMI SE of the MPT membrane by ∼ 1.6 times compared to other TPU-based membrane. MPT strain sensor exhibits great sensing performance with a remarkable detection threshold of 0.1%, strain coefficient of up to 2600, broad working range of 200%, and rapid response/recovery time (77/186 ms). Meanwhile, MPT strain sensor also shows remarkable ability to real-time monitor human health/motion, such as joint bending, breathing, speaking and heart rate, which makes significant contributions in the field of smart medicine. This nanofiber membrane can provide a universal strategy for the development of intelligent wearable medical devices.

Frontiers in biomedical research

With continuous breakthroughs in basic research and technological innovation in the field of biomedicine, we have a much deeper understanding of the nature of life and disease pathogenesis. New medical technologies, medicines and medical instruments are emerging, which greatly promote diagnosis, treatment, prevention and healthy lifestyle. Focusing on international engagement together with the development needs of individual businesses is a major task for China's biomedical community in order to achieve high-quality outcomes. This paper emphasizes the need to further strengthen the cross-integration and development of medical science in China, realize the paradigm change of medical research, and promote the development and application of revolutionary medical technologies, diagnostics, drugs and medical devices. Eighteen frontier hot spots and common issues are highlighted for the field of biomedicine.

3D-PRINTED ABSORBABLE METALLIC MEDICAL DEVICES AND THEIR APPLICATION POTENTIAL

AM specifically allows for cost-efficient production of patient-specific Orthopaedic medical devices with unusual designs and properties. A porous design allows to adjust the stiffness of metallic implants to that of the host bone. Beyond traditional metals, like titanium alloys, this talk will review the present state-of-the-art of directly printed absorbable metal families. Physicochemical, mechanical and biological properties of standardized design prototypes from all currently available metal families will be compared and their clinical application potential discussed. The impact of in vitro test environments on comparative corrosion behavior, post manufacturing aspects, and the recent status quo in biocompatibility testing and present knowledge gaps will be addressed.

Selection and evaluation of a MES software for a 3D printing center at point of care

3D printing at point of care is an emerging business and many hospitals are on their way of becoming manufacturers of medical devices. In order to comply with medical regulations, production processes need to be managed and documented. Although various manufacturing execution systems (MES) exist for general purpose applications, the medical domain in combination with novel additive manufacturing processes poses special issues, requirements, and adaptation needs to these systems. In this paper we present a structured framework to select and evaluate an appropriate MES software for a 3D printing center at point of care. The results are based on a real-world case of a 3D printing center in a hospital and provide practical and theoretical insights on the selection and evaluation process in this novel manufacturing domain.

Kickbacks, Courtesies or Cost-Effectivness:Application of the Medicare Antikickback Law to the Marketing and PromotionalPractices of Drug and Medical Device Manufacturers

Kickbacks, Courtesies or Cost-Effectivness:Application of the Medicare Antikickback Law to the Marketing and PromotionalPractices of Drug and Medical Device Manufacturers

Integration of SAP PS with Legacy Systems in Medical Device Manufacturing: A Comparative Study

Integration of SAP PS with Legacy Systems in Medical Device Manufacturing: A Comparative Study

Virtual Surgical Planning for Point-of-Care Manufacturing

Two factors motivating the achievement of safe and effective Point-of-Care Manufacturing (POCM) are (1) to provide personalized medical devices to patients with short treatment windows (e.g., trauma, advanced stage cancer) and (2) to ensure that those devices improve outcomes and reduce revision surgery rates. In-hospital use of Virtual Surgical Planning (VSP) now commonly includes the production of surgical models and procedure guides (e.g., cutting, drilling, or placement guides and tool jigs). As this technology becomes widely available, we envision the FDA approving VSP software with tools for personalized, implantable, medical device design and POCM. Indeed, VSP for local optimization of device shape (external surfaces and internal pore geometry), placement (anatomical location), materials (via interactive simulation of post-operative device performance), and the fabrication process engineering plan can be executed in real time. This is nothing short of a paradigm shift from manual personalization of off-the-shelf devices or the factory-based fabrication of personalized medical devices. As an example of this new paradigm, we present here a hypothetical VSP pathway for the design and POCM of personalized mandibular graft fixation devices where optimized performance avoids both stress shielding-induced bone loss as well as stress concentration-induced device failure.

Intestinal retentive systems - recent advances and emerging approaches.

Intestinal retentive devices (IRDs) are devices designed to anchor within the lumen of the intestines for long-term residence in the gastrointestinal tract. IRDs can enable impactful medical device technologies including sustained oral drug delivery systems, indwelling sensors, or real-time diagnostics. The design and testing of IRDs present a myriad of challenges, including precise deployment of the device at desired intestinal locations, secure anchoring within the gastrointestinal tract to allow for natural function, and safe removal of the IRD at user-defined times. Advancing the state-of-the-art of IRD is an interdisciplinary effort that requires innovations such as new materials, novel anchoring mechanisms, and medical device design with consistent input from clinical practitioners and end-users. This perspective briefly reviews the current state-of-the-art for IRDs and charts a path forward to inform the design of future concepts. Specifically, this article will highlight materials, retention mechanisms, and test beds to measure the efficacy of IRDs and their mechanisms. Finally, potential synergies between IRD and other medical device technologies are presented to identify future opportunities.

Quasi-experimental design for external control arm studies alongside single arm trials for regulatory purposes

To accelerate new drug, biologic, and medical device development and to improve efficiency of delivery of the latest breakthroughs of innovative, life-saving treatments to millions of patients, single-arm trial (SAT) applications of rare diseases or conditions supplemented by their external control arm (ECA) evidence for regulatory approvals have been surging since 2016. However, there have been increasing concerns over potential biases threatening the internal validity of these applications from regulatory authorities, payers, and research community. There are two main sources of potential biases. The first source is heterogeneity between two arms at the level of patients, and the second one at the level of systems (e.g., two entirely different sets of hospitals from which patients in a SAT and patients in an ECA are drawn separately). The currently commonly used study design is a post-intervention measurement only design that though mitigating the first source of bias, is utterly unable to control for the second one. This perspective article will propose a quasi-experimental design as an alternative that may mitigate the second source of bias, aiming to improve the internal validity of SAT and ECA studies. We will start summarizing the two main sources of biases that may impede the causal inference of these studies. Two approved therapies supported by SAT and ECA studies will be used as an example to illustrate these biases in detail. We will then introduce the intuition of the quasi-experimental design, underlying assumptions and data requirements, and empirical strategies for estimating interventional effects. We will conclude this article by discussing caveats of applying this alternative design for SAT and ECA studies.

Case-Specific Unruptured Intracranial Aneurysm Simulation for New Medical Device Development: Validation of the First Fully Functional Additively Manufactured Aneurysm Clip

Case-Specific Unruptured Intracranial Aneurysm Simulation for New Medical Device Development: Validation of the First Fully Functional Additively Manufactured Aneurysm Clip

Current Considerations and Practical Solutions for Overcoming Nanoparticle Interference with LAL Assays and Minimizing Endotoxin Contamination.

Monitoring endotoxin contamination in drugs and medical devices is required to avoid pyrogenic responses and septic shock in patients receiving these products. Endotoxin contamination of engineered nanomaterials and nanotechnology-based medical products represents a significant translational hurdle. Nanoparticles often interfere with an in vitro limulus amebocyte lysate (LAL) assay commonly used in the pharmaceutical industry for the detection and quantification of endotoxin. Such interference challenges the preclinical development of nanotechnology-formulated drugs and medical devices containing engineered nanomaterials. Protocols for the analysis of nanoparticles using LAL assays have been reported before. Here, we discuss considerations for selecting an LAL format and describe a few experimental approaches for overcoming nanoparticle interference with the LAL assays to obtain more accurate estimations of endotoxin contamination in nanotechnology-based products. The discussed approaches do not solve all types of nanoparticle interference with the LAL assays but could be used as a starting point to address the problem. This chapter also describes approaches to prevent endotoxin contamination in nanotechnology-formulated products.

3D printing for Growth Adaptive Medical Devices: an alternative approach for craniosynostosis

An adaptive medical device is a piece of equipment designed to adjust or respond to changes in a patient’s condition or environment. The use of 3D printing technology for the development of adaptive medical devices has opened up new possibilities for customization, efficiency, and accessibility in healthcare. Sagittal craniosynostosis is a birth defect that arises due to a premature fusion of the sagittal suture in infants. This disease causes a misshapen skull and a rise of intracranial pressure that can lead to cognitive impairments. At six months of age, the preferred technique for craniosynostosis is an open vault remodeling surgery, an extremely invasive procedure with severe blood loss for the patient and significant postoperative pain. In this context, growth adaptive cranial plates, that can be tuned depending on the patient to achieve the desired skull shape through the deformation of the structure, can be a valid alternative. Cellular and lattice structures offer tailorable mechanical properties in relation to the designed geometry. Specifically, the geometry of cellular materials can be modified in relation to the final mechanical requirements. In this study, the predictability of the deformation of a PLA structure composed by honeycomb unit cells was studied performing compression simulations. The geometry was then modified, simulations and compression tests were then repeated in order to find an equation that could describe the relation between the internal angle of the honeycomb and the relative Poisson ratio. This relation can be further exploited for the production of customized adaptive devices for the treatment of sagittal craniosynostosis.

Assessment of the gender gap in urology industry payments: An Open Payments Program data analysis.

The Open Payments Program (OPP), established in 2013 under the Sunshine Act, mandated medical device and pharmaceutical manufacturers to submit records of financial incentives given to physicians for public availability. The study aims to characterize the gap in real general and real research payments between man and woman urologists. The study sample included all urologists in the United States who received at least one general or research payment in the OPP database from 2015 to 2021. Recipients were identified using the National Provider Identifier and National Downloadable File datasets. Payments were analyzed by geography, year, payment type, and years since graduation. Multivariable analysis on odds of being in above the median in terms of money received was done with gender as a covariate. This analysis was also completed for all academic urologists. There was a total of 15,980 urologists; 13.6% were woman, and 86.4% were man. Compared to man urologists, woman urologists were less likely to be in the top half of total payments received (odds ratio [OR] 0.62) when adjusted for other variables. When looking at academic urologists, 18.1% were woman and 81.9% were man. However, woman academic urologists were even less likely to be in the top 50% of payments received (OR 0.55). This study is the first to characterize the difference in industry payments between man and woman urologists. The results should be utilized to educate physicians and industry, in order to achieve equitable engagement and funding for woman urologists.

A dual analysis of bougie and stylet development trend and impact of Chinese regulations on medical devices innovation.

Medical device research and development are characterized by high costs, extended timelines, inherent risks, and the necessity for interdisciplinary knowledge and skills. It is significantly influenced by policies, making the understanding of medical device innovation both important and challenging. This paper takes a dual approach to analyze medical device innovation. We reviewed representative clinical product of bougie and stylet and summarized the common characteristics and trend of these product. Innovations in these products often involve adding depth markings, replacing material and design structure, enhancing visualization, deciding between reusable or disposable designs, and integrating multi-functional features. This underscores the delicate balance between technological advancements and medical costs for widespread clinical applicability. We explored the guiding role of policy in medical device innovation, emphasizing its impact through an analysis of medical device regulations and policies in China. By offering insights from the perspectives of medical device companies and regulators, this paper aims to elucidate the critical aspects of medical device innovation, assisting researchers in mitigating risks during product development.

Surface disinfection change the mechanical, structural and biological properties of flexible materials used for additive manufacturing of medical devices

Additive manufacturing (AM) is a versatile technology with potential applications in healthcare and medical instruments, where surface disinfection or sterilization is essential. This study comprehensively the effect of commonly used cost-effective disinfectants, ethanol (70 V/V%) and chlorine solution on the mechanical and thermal properties of flexible 3D printed materials. The following materials were tested before and after a 5-cycle surface disinfection: Flexfill TPE 90A, Phyton Flex (TPU) for material extrusion, Flexible (resin), Elastic 50A (resin) for vat photopolymerization and Flexa Black (TPU) material for powder bed fusion technology. Mechanical tests included tensile, compression, Charpy impact, flex resistance and stress relaxation tests, as well as Shore A hardness and volume measurements. The structure was analyzed using scanning electron microscopy (SEM)and Raman spectroscopy. The cytotoxicity was assessed using a A549 cell viability assay. The results show that after disinfection, significant changes occurred mainly in the tensile and Shore A properties, such as the tensile strength of the disinfected Flexible (resin) materials was 3.44 MPa ± 0.51 MPa (ethanol) and 2.62 MPa ± 0.31 MPa compared to the native 2.02 MPa ± 0.24 MPa. Interestingly, the applied surface disinfectants can negatively affect biocompatibility. Medical devices have been designed and fabricated based on the findings. Our findings can serve as a guide to the potential applications of commonly used 3D printed flexible materials in the biomedical field.

Development of Medical Devices Utilizing Mechatronics Technology

Development of Medical Devices Utilizing Mechatronics Technology

Early technology review: towards an expedited pathway.

Evidence development for medical devices is often focused on satisfying regulatory requirements with the result that health professional and payer expectations may not be met, despite considerable investment in clinical trials. Early engagement with payers and health professionals could allow companies to understand these expectations and reflect them in clinical study design, increasing chances of positive coverage determination and adoption into clinical practice. An example of early engagement through the EXCITE International model using an early technology review (ETR) is described which includes engagement with payers and health professionals to better inform companies to develop data that meet their expectations. ETR is based on an early evidence review, a framework of expectations that guides the process and identified gaps in evidence. The first fourteen ETRs were reviewed for examples of advice to companies that provided additional information from payers and health professionals that was thought likely to impact on downstream outcomes or strategic direction. Given that limitations were imposed by confidentiality, examples were genericized. Advice through early engagement can inform evidence development that coincides with expectations of payers and health professionals through a structured, objective, evidence-based approach. This could reduce the risk of business-related adverse outcomes such as failure to secure a positive coverage determination and/or acceptance by expert health professionals. Early engagement with key stakeholders exemplified by the ETR approach offers an alternative to the current approach of focusing on regulatory expectations. This could reduce the time to reimbursement and clinical adoption and benefit patient outcomes and/or health system efficiencies.