Process,Material,and Regulatory Considerations for 3D Printed Medical Devices and Tissue Constructs

Three-dimensional(3D)printing is a highly automated platform that facilitates material deposition in a layer-by-layer approach to fabricate pre-defined 3D complex structures on demand.It is a highly promising technique for the fabrication of personalized medical devices or even patient-specific tissue constructs.Each type of 3D printing technique has its unique advantages and limitations,and the selection of a suitable 3D printing technique is highly dependent on its intended application.In this review paper,we present and highlight some of the critical processes(printing parameters,build orientation,build location,and support structures),material(batch-to-batch consistency,recycling,protein adsorption,biocompatibility,and degradation properties),and regulatory considerations(sterility and mechanical properties)for 3D printing of personalized medical devices.The goal of this review paper is to provide the readers with a good understanding of the various key considerations(process,material,and regulatory)in 3D printing,which are critical for the fabrication of improved patient-specific 3D printed medical devices and tissue constructs.

Research on Patent Situation of Medical Devices in China

Objective To study the patent situation of medical device industry in China based on patent data.Methods The analysis function of the patent search software incoPat was used to analyze the patent situation from two perspectives:The overall situation and the technical level.Results and Conclusion At present,China’s medical device industry is developing rapidly under the leadership of enterprises as the main body of innovation,but only 16%of patents are authorized.In addition,the technology distribution of medical device industry is mainly related to diagnostic,surgical and identification medical devices and implantable devices,accounting for 59%of the main technology distribution,and their technical effects are mainly related to improving convenience,reducing complexity,and improving safety.The quality of patents related to medical device industry in China is low,the technology distribution is not rich enough,and the level of technical efficacy is low.

Balancing the customization and standardization:exploration and layout surrounding the regulation of the growing field of 3D-printed medical devices in China

Medical devices are instruments and other tools that act on the human body to aid clinical diagnosis and disease treatment,playing an indispensable role in modern medicine.Nowadays,the increasing demand for personalized medical devices poses a significant challenge to traditional manufacturing methods.The emerging manufacturing technology of three-dimensional(3D)printing as an alternative has shown exciting applications in the medical field and is an ideal method for manufacturing such personalized medical devices with complex structures.However,the application of this new technology has also brought new risks to medical devices,making 3D-printed devices face severe challenges due to insufficient regulation and the lack of standards to provide guidance to the industry.This review aims to summarize the current regulatory landscape and existing research on the standardization of 3D-printed medical devices in China,and provide ideas to address these challenges.We focus on the aspects concerned by the regulatory authorities in 3D-printed medical devices,highlighting the quality system of such devices,and discuss the guidelines that manufacturers should follow,as well as the current limitations and the feasible path of regulation and standardization work based on this perspective.The key points of the whole process quality control,performance evaluation methods and the concept of whole life cycle management of 3D-printed medical devices are emphasized.Furthermore,the significance of regulation and standardization is pointed out.Finally,aspects worthy of attention and future perspectives in this field are discussed.

Integrity Assessment of Medical Devices for Improving Hospital Services

The present study examines the various techniques being used to maintain the integrity of the medical devices,and develops a quantitative framework to list these in the sequence of priority.To achieve the intended objective,the study employs the combined procedure of Fuzzy Analytic Network Process(ANP)and Fuzzy Technical for Order Preference by Similarities to Ideal Solution(TOPSIS).We selected fuzzy based decision making techniques for assessing the integrity of medical devices.The suggested methodology was then used for classifying the suitable techniques used to evaluate the integrity of medical devices.Different techniques or the procedures of integrity assessment were ranked according to their satisfaction weights.The rating of the options determined the order of priority for the procedures.As per the findings of the study,among all the options,A1 was assessed to be the most likely option.This means that the integrity of medical devices of A2 is the highest amongst all the chosen alternatives.This analysis will be a corroborative guideline for manufacturers and developers to quantitatively test the integrity of medical devices in order to engineer efficacious devices.The evaluations undertaken with the assistance of the planned procedure are accurate and conclusive.Hence instead of conducting a manual valuation,this experimental study is a better and reliable option for assessing the integrity of the medical devices.

Bioinspired Functional Surfaces for Medical Devices

Medical devices are a major component of precision medicine and play a key role in medical treatment,particularly with the rapid development of minimally invasive surgery and wearable devices.Their tissue contact properties strongly affect device performance and patient health(e.g.,heat coagulation and slipperiness on surgical graspers).However,the design and optimization of these device surfaces are still indistinct and have no supporting principles.Under such conditions,natural surfaces with various unique functions can provide solutions.This review summarizes the current progress in natural functional surfaces for medical devices,including ultra-slipperiness and strong wet attachment.The underlying mechanisms of these surfaces are attributed to their coupling effects and featured micronano structures.Depending on various medical requirements,adaptable designs and fabrication methods have been developed.Additionally,various medical device surfaces have been validated to achieve enhanced contact properties.Based on these studies,a more promising future for medical devices can be achieved for enhanced precision medicine and human health.

Application of Real-World Evidence in Regulatory Decision-Making for Medical Devices

Objective To understand the real-world study(RWS)and its application in domestic and foreign pharmaceutical device regulatory decision-making,so as to promote its further application in the decision-making of medical devices supervision in China.Methods Literature analysis and comparative analysis were used to compare the real-world evidence(RWE)and randomized controlled trials to obtain the development status of medical devices in China and the United States.Results and Conclusion It is found that the application of RWS in the field of medical devices has many advantages,which can make up for the deficiencies of traditional clinical data.In addition,the RWE has a wide range of applications in the field of medical devices in China.In recent years,the RWE has received extensive attention in the medical field in the United States.The FDA has issued related guidelines,and its applications have gradually formed a complete system.Research on RWE will become the development trend of clinical evaluation of medical devices in the future.While attaching importance to the development of the RWE,China should learn from the specifications of relevant foreign organizations to improve its development in the field of health.

Mechanical Design of Long-Term Body-Adhered Medical Devices to Maximize On-Body Survival

Long-term, body-adhered medical devices rely on an adhesive interface to maintain contact with the patient. The greatest threat to on-body adhesion is mechanical stress imparted on the medical device. Several factors contribute to the ability of the device to withstand such stresses, such as the mechanical design, shape, and size of the device. This analysis investigates the impact that design changes to the device have on the stress and strain experienced by the system when acted on by a stressor. The analysis also identifies the design changes that are most effective at reducing the stress and strain. An explicit dynamic finite element analysis method was used to simulate several design iterations and a regression analysis was performed to quantify the relationship between design and resultant stress and strain. The shape, height, size, and taper of the medical device were modified, and the results indicate that, to reduce stress and strain in the system, the device should resemble a square in shape, be short in height, and small in size with a large taper. The square shape experienced 17.5% less stress compared to the next best performing shape. A 10% reduction in device height resulted in a 21% reduction in stress and 24% reduction in strain. A 20% reduction in device size caused a 7% reduction in stress and 2% reduction in strain. A 20% increase in device taper size led to a negligible reduction in stress and a 6% reduction in strain. The height of the device had the greatest impact on the resultant stress and strain.

Bayesian approach for design and analysis of medical device trials in the era of modern clinical studies

Medical device technology develops rapidly,and the life cycle of a medical device is much shorter than drugs.It is necessary to evaluate the safety and effectiveness ofamedical device in a timelymanner to keep upwith technology flux.Bayesian methods provides an efficient approach to addressing this challenge.In this article,we review the characteristics of the Bayesian approach and some Bayesian designs that were commonly used in medical device regulatory setting,including Bayesian adaptive design,Bayesian diagnostic design,Bayesian multiregional design,and Bayesian label expansion study.We illustrate these designs with medical devices approved by the US Food and Drug Administration(FDA).We also review several innovative Bayesian information borrowing methods,and briefly discuss the challenges and future directions of the Bayesian application in medical device trials.Our objective is to promote the use of the Bayesian approach to accelerate the development of innovative medical devices and their accessibility to patients for effective disease diagnoses and treatments.

Bibliometric analysis of the literature from the mainland of China on animal-derived regenerative implantable medical devices

Choosing animal-derived regenerative implantable medical devices based on tissue engineering technology as a research theme, this paper presents bibliometric analysis of relative literature from the mainland of China to understand such data as publication year and journal preference, authors＇ geographic location, research topics and core expertise to predict the research trends and provide an informed basis of decision making for researchers and clinicians.

Analysis of intellectual properties on animalderived regenerative, implantable medical devices

This article analyses and summarizes issues of intellectual property involved in animal-derived regenerative,implantable medical devices(ADRIMD)in order to better understand global trends in patent applications and disclosures,the legal status of patent families(i.e.sets of patents filed in various countries to protect a single invention),and International Patent Classification topics such as main assignee and core expertise.Analysis of research trends will enhance and inform the decision-making capacity of researchers,investors,government regulators and other stake-holders as they undertake to develop,deploy,invest in or regulate ADRIMD.

A review of the bio-tribology of medical devices

Numerous medical devices have been applied for the treatment or alleviation of various diseases.Tribological issues widely exist in those medical devices and play vital roles in determining their performance and service life.In this review,the bio-tribological issues involved in commonly used medical devices are identified,including artificial joints,fracture fixation devices,skin-related devices,dental restoration devices,cardiovascular devices,and surgical instruments.The current understanding of the bio-tribological behavior and mechanism involved in those devices is summarized.Recent advances in the improvement of tribological properties are examined.Challenges and future developments for the prospective of bio-tribological performance are highlighted.

Secure Method for Software Upgrades for Implantable Medical Devices

A non-invasive software upgrade method for permanent implantable medical devices was developed to alleviate patients＇ suffering due to malfunctions because of software faults,which may cause serious adverse health consequences or require enhancements with new software.The programs distributed to the internal implantable pulse generator（IPG） from the external programmer have been developed so that the upgrade service program in the IPG is simplified with most complex functions executed by the external programmer.A bidirectional protocol including frame definition and transmission mode was designed to insure secure upgrades.A neuro-stimulator was used to verify the upgrade solution with no additional elements,to maintain the hardware reliability.This study emphasizes how to insure a secure and stable upgrade process and reduce power consumption for special wireless and life safety-critical applications.Tests on rhesus monkeys to evaluate the feasibility of the approach for an IPG used for brain stimulation evaluation show that the software upgrade can be implemented stably with good tolerance to the wireless data transmissions.

Key considerations on the development of biodegradable biomaterials for clinical translation of medical devices:With cartilage repair products as an example

With the interdisciplinary convergence of biology,medicine and materials science,both research and clinical translation of biomaterials are progressing at a rapid pace.However,there is still a huge gap between applied basic research on biomaterials and their translational products-medical devices,where two significantly different perspectives and mindsets often work independently and non-synergistically,which in turn significantly increases financial costs and research effort.Although this gap is well-known and often criticized in the biopharmaceutical industry,it is gradually widening.In this article,we critically examine the developmental pipeline of biodegradable biomaterials and biomaterial-based medical device products.Then based on clinical needs,market analysis,and relevant regulations,some ideas are proposed to integrate the two different mindsets to guide applied basic research and translation of biomaterial-based products,from the material and technical perspectives.Cartilage repair substitutes are discussed here as an example.Hopefully,this will lay a strong foundation for biomaterial research and clinical translation,while reducing the amount of extra research effort and funding required due to the dissonance between innovative basic research and commercialization pipeline.

Design and analysis of high-risk medical device clinical trials for diabetes monitoring and treatment: a review

Class III medical devices are those devices that support or sustain human life or prevent impairment of human health but,when used,pose high risks to the patients.There were 15 class III medical devices that were approved by the US Food and Drug Administration from September 1,2005 to December 31,2018 for glucose monitoring and diabetes treatment.In this article,we reviewed the study design and statistical analysis in clinical trials that were conducted to provide evidences for safety and effectiveness of these medical devices.Two exemplars of clinical trials for"Eversense continuous glucose monitoring system"and"t:slim X2 Insulin Pump with Basal-IQ Technology"are discussed in details.

A high-efficiency charge pump in BCD process for implantable medical devices

This paper presents a high-efficiency charge pump circuit composed of cascaded cross-coupled voltage doublers implemented in an isolated bipolar-CMOS-DMOS（BCD） technology for implantable medical devices.Taking advantage of the transistor structures in the isolated BCD process, the leakage currents caused by the parasitic PNP transistors in the cross-coupled PMOS serial switches are eliminated by simply connecting the inside substrate terminal to the isolation terminal of each PMOS transistor. The simple circuit structure leads to small parasitic capacitance in the voltage doubler, which in turn ensures high efficiency of the overall charge pump. The proposed charge pump with 5 cascaded voltage doublers is fabricated in a 0.35-μm isolated BCD process. Measurement results with 2-V power supply, 1-MHz driving clock frequency and 40-μA current load show that an efficiency of 72.6% is achieved, and the output voltage can be pumped to about 11.5 V at zero load current. The chip area of the charge pump is 1.6 × 0.35 mm^2.

Bioinspired approaches for medical devices

Advances in medical devices have revolutionized the treatment of human diseases,such as stents in occluded coronary artery,left ventricular assist devices in heart failure,pacemakers in arrhythmias,etc.Despite their significance,the development of devices for reducing and avoiding the thrombosis formation,obtaining excellent mechanical performance,and achieving stable electronic physiology remains challenging and unresolved.Fortunately,nature serves as a good resource of inspirations,and brings us endless bioinspired physicochemical ideas to better the development of novel artificial materials and devices that enable us to potentially overcome the unresolved obstacles.Bioinspired approaches,in particularly,owe much of their current development in biology,chemistry,materials science,medicine and engineering to the design and fabrication of advanced devices.The application of bioinspired devices is a burgeoning area in these fields of research.In this perspective,we would take the cardiovascular device as one example to show how these bioinspired approaches could be used to build novel,advanced biomedical devices with precisely controlled functions.Here,bioinspired approaches are utilized to solve issues like thrombogenic,mechanical and electronic physiology problems in medical devices.Moreover,there is an outlook for future challenges in the development of bioinspired medical devices.

Medical Devices Standardization System in China

The standardization system is imperfect since the complexity of the medical devices and the specialty of the medical device industry in China. This paper describes the present situation of medical devices standardization system in China,reviews and discusses the advantages and problems of the medical devices standardizatiom. It also presents some comments and suggestions to perfect the medical devices standardization system for enhancing the quality control of medical devices and for promoting the development of medical devices industry.

Design of Fine Life Cycle Prediction System for Failure of Medical Equipment

The inquiry process of traditional medical equipment maintenance management is complex,which has a negative impact on the efficiency and accuracy of medical equipment maintenance management and results in a significant amount of wasted time and resources.To properly predict the failure of medical equipment,a method for failure life cycle prediction of medical equipment was developed.The system is divided into four modules:the whole life cycle management module constructs the life cycle data set of medical devices from the three parts of the management in the early stage,the middle stage,and the later stage;the status detection module monitors the main operation data of the medical device components through the normal value of the relevant sensitive data in the whole life cycle management module;and the main function of the fault diagnosis module is based on the normal value of the relevant sensitive data in the whole life cycle management module.The inference machine diagnoses the operation data of the equipment;the fault prediction module constructs a fine prediction system based on the least square support vector machine algorithm and uses the AFS-ABC algorithm to optimize the model to obtain the optimal model with the regularized parameters and width parameters;the optimal model is then used to predict the failure of medical equipment.Comparative experiments are designed to determine whether or not the design system is effective.The results demonstrate that the suggested system accurately predicts the breakdown of ECG diagnostic equipment and incubators and has a high level of support and dependability.The design system has the minimum prediction error and the quickest program execution time compared to the comparison system.Hence,the design system is able to accurately predict the numerous causes and types of medical device failure.

Preparation of Air Film for Medical Infusion Device and Study on Air Permeability and Water Resistance

Polypropylene melt-blown nonwoven was used as the substrate for the preparation of an air film. The nonwoven was immersed in the casting solution at first,and then respectively placed in the first coagulation bath,the second coagulation bath and the finishing liquid containing fluorine additive aqueous solution of 20 g/L. At last,the high temperature drying was carried out to obtain the air permeable and water resistant air film. With analyses and comparisons of the isopropanol alcohol content,the residence time of air,the composition of the first coagulation bath and the residence time of the first coagulation,the optimum parameters were found and the air film had an air permeability of 4. 7 L/min,a water blocking pressure of 16 kPa,a contact angle of 134. 2°,and a mean pore size of 2. 089 1 μm.