Manufacturing Of Biomedical Devices Research Articles

Lysine grafted poly(lactic acid): An intrinsically antimicrobial polymer

Nosocomial infections or healthcare-associated infections, normally develops after the healthcare treatment in the hospital. Most of them are caused by infected medical devices. Plastics are the most common materials for manufacturing these devices because of their good processability, sterilization efficacy, ease of handling and harmlessness, however, it usually do not display antimicrobial properties. Here, in order to infer antimicrobial activity to poly(lactic acid), it was modified by maleation, followed by l-lysine grafting to its structure. The chemical modifications were confirmed by FTIR and 1H NMR analysis, indicating the success of the reactions. The antimicrobial activity was tested using Escherichia coli and Staphylococcus aureus and the results showed that the sample was capable of inhibiting about 99 % of the S. aureus growth by contact. The samples cytotoxicity was also tested using the L929 mouse cells and the results indicated no cytotoxic effect. These results indicated the sample antimicrobial potential, without affect the normal eukaryotic cells. In addition, the processability of the modified PLA (PLA-g-Lys) was improved without compromising its mechanical properties, as shown by thermal analysis and tensile tests. Thus, this novel PLA derivative can be seen as a promising material for future applications in the manufacturing of biomedical devices.

Review of Piezoelectrical Materials Potentially Useful for Peripheral Nerve Repair.

It has increasingly been recognized that electrical currents play a pivotal role in cell migration and tissue repair, in a process named "galvanotaxis". In this review, we summarize the current evidence supporting the potential benefits of electric stimulation (ES) in the physiology of peripheral nerve repair (PNR). Moreover, we discuss the potential of piezoelectric materials in this context. The use of these materials has deserved great attention, as the movement of the body or of the external environment can be used to power internally the electrical properties of devices used for providing ES or acting as sensory receptors in artificial skin (e-skin). The fact that organic materials sustain spontaneous degradation inside the body means their piezoelectric effect is limited in duration. In the case of PNR, this is not necessarily problematic, as ES is only required during the regeneration period. Arguably, piezoelectric materials have the potential to revolutionize PNR with new biomedical devices that range from scaffolds and nerve-guiding conduits to sensory or efferent components of e-skin. However, much remains to be learned regarding piezoelectric materials, their use in manufacturing of biomedical devices, and their sterilization process, to fine-tune their safe, effective, and predictable in vivo application.

A Poly-(ethylene glycol)-diacrylate 3D-Printed Micro-Bioreactor for Direct Cell Biological Implant-Testing on the Developing Chicken Chorioallantois Membrane.

Advancements in biomaterial manufacturing technologies calls for improved standards of fabrication and testing. Currently 3D-printable resins are being formulated which exhibit the potential to rapidly prototype biocompatible devices. For validation purposes, 3D-printed materials were subjected to a hierarchical validation onto the chorioallantoic membrane of the developing chicken, better known as the HET CAM assay. Working along these lines, prints made from poly-(ethylene glycol)-diacrylate (PEGDA), which had undergone appropriate post-print processing, outperformed other commercial resins. This material passed all tests without displaying adverse effects, as experienced with other resin types. Based on this finding, the micro bioreactors (MBR) design, first made of PDMS and that also passed with cell tests on the HET-CAM, was finally printed in PEGDA, and applied in vivo. Following this workflow shows the applicability of 3D-printable resins for biomedical device manufacturing, consents to adherence to the present standards of the 3R criteria in material research and development, and provides flexibility and fast iteration of design and test cycles for MBR adaptation and optimization.

High-resolution fabrication of nanopatterns by multistep iterative miniaturization of hot-embossed prestressed polymer films and constrained shrinking

The fabrication of nanostructures and nanopatterns is of crucial importance in microelectronics, nanofluidics, and the manufacture of biomedical devices and biosensors. However, the creation of nanopatterns by means of conventional nanofabrication techniques such as electron beam lithography is expensive and time-consuming. Here, we develop a multistep miniaturization approach using prestressed polymer films to generate nanopatterns from microscale patterns without the need of complex nanolithography methods. Prestressed polymer films have been used as a miniaturization technique to fabricate features with a smaller size than the initial imprinted features. However, the height of the imprinted features is significantly reduced after the thermal shrinking of the prestressed films due to the shape memory effect of the polymer, and as a result, the topographical features tend to disappear after shrinking. We have developed a miniaturization approach that controls the material flow and maintains the shrunken patterns by applying mechanical constraints during the shrinking process. The combination of hot embossing and constrained shrinking makes it possible to reduce the size of the initial imprinted features even to the nanoscale. The developed multistep miniaturization approach allows using the shrunken pattern as a master for a subsequent miniaturization cycle. Well-defined patterns as small as 100 nm are fabricated, showing a 10-fold reduction in size from the original master. The developed approach also allows the transfer of the shrunken polymeric patterns to a silicon substrate, which can be used as a functional substrate for many applications or directly as a master for nanoimprint lithography.

How to Sterilize Polylactic Acid Based Medical Devices?

How sterilization techniques accurately affect the properties of biopolymers continues to be an issue of discussion in the field of biomedical engineering, particularly now with the development of 3D-printed devices. One of the most widely used biopolymers in the manufacture of biomedical devices is the polylactic acid (PLA). Despite the large number of studies found in the literature on PLA devices, relatively few papers focus on the effects of sterilization treatments on its properties. It is well documented in the literature that conventional sterilization techniques, such as heat, gamma irradiation and ethylene oxide, can induced damages, alterations or toxic products release, due to the thermal and hydrolytical sensitivity of PLA. The purposes of this paper are, therefore, to review the published data on the most common techniques used to sterilize PLA medical devices and to analyse how they are affecting their physicochemical and biocompatible properties. Emerging and alternative sterilization methods for sensitive biomaterials are also presented.

Photopolymerization of Bio-Based Polymers in a Biomedical Engineering Perspective.

Photopolymerization is an effective method to covalently cross-link polymer chains that can be shaped into several biomedical products and devices. Additionally, polymerization reaction may induce a fluid-solid phase transformation under physiological conditions and is ideal for in vivo cross-linking of injectable polymers. The photoinitiator is a key ingredient able to absorb the energy at a specific light wavelength and create radicals that convert the liquid monomer solution into polymers. The combination of photopolymerizable polymers, containing appropriate photoinitiators, and effective curing based on dedicated light sources offers the possibility to implement photopolymerization technology in 3D bioprinting systems. Hence, cell-laden structures with high cell viability and proliferation, high accuracy in production, and good control of scaffold geometry can be biofabricated. In this review, we provide an overview of photopolymerization technology, focusing our efforts on natural polymers, the chemistry involved, and their combination with appropriate photoinitiators to be used within 3D bioprinting and manufacturing of biomedical devices. The reviewed articles showed the impact of different factors that influence the success of the photopolymerization process and the final properties of the cross-linked materials.

Aging of Solvent-Casting PLA-Mg Hydrophobic Films: Impact on Bacterial Adhesion and Viability

Biomaterials used for the manufacture of biomedical devices must have suitable surface properties avoiding bacterial colonization and/or proliferation. Most biomaterial-related infections start during the surgery. Bacteria can begin colonization of the surface of a device right after implantation or in the next few hours. This time may also be sufficient to begin the deterioration of a biodegradable implant. This work explores the surface changes that hydrophobic films of poly(lactic) acid reinforced with Mg particles, prepared by solving-casting, undergone after in vitro degradation at different times. Hydrophobicity, surface tension, zeta potential, topography, and elemental composition were obtained from new and aged films. The initial degradation for 4 h was combined with unspecific bacterial adhesion and viability tests to check if degraded films are more or less susceptible to be contaminated. The degradation of the films decreases their hydrophobicity and causes the appearance of a biocompatible layer, composed mainly of magnesium phosphate. The release of Mg2+ is very acute at the beginning of the degradation process, and such positive charges may favor the electrostatic approach and attachment of Staphylococci. However, all bacteria attached on the films containing Mg particles appeared damaged, ensuring the bacteriostatic effect of these films, even after the first hours of their degradation.

Assessment of the Physicochemical and Thermal Characterization of Biofield Energy Treated Polylactic-co-glycolic acid (PLGA)

Polylactic-co-glycolic acid (PLGA) is a biodegradable copolymer. It has many applications in the pharmaceuticals and biomedical industries, but its degradation and stability is a major concern. The objective of this study was to evaluate the influence of the Trivedi Effect® on the physicochemical and thermal properties of PLGA using modern analytical techniques. The PLGA sample was divided into control and Biofield Energy Treated parts. The control sample did not obtain the Biofield Energy Treatment, whereas the treated PLGA was received the Trivedi Effect®-Consciousness Energy Healing Treatment remotely by a renowned Biofield Energy Healer, Alice Branton. The particle size values of the treated PLGA were increased by 8.97%(d10), 8.79%(d50), 4.72%(d90), and 6.61%{D(4,3)}; thus, the surface area of treated PLGA was significantly decreased by 6.84% compared with the control sample. The latent heat of evaporation and fusion of the treated PLGA were significantly increased by 29.60% and 230.93%, respectively compared with the control sample. The residue amount was significantly increased by 21.99% in the treated PLGA compared to the control sample. The maximum thermal degradation temperature of the treated PLGA was increased by 2.30% compared with the control sample. It was concluded that the Trivedi Effect®-Consciousness Energy Healing Treatment might have generated a new form of PLGA which may show better powder flow ability, thermal stability, and minimize the hydrolysis of the ester linkages of PLGA. This improved quality of PLGA would be a better choice for the pharmaceutical formulations (i.e., the drug like simvastatin, amoxicillin, and minocycline loaded PLGA nanoparticles) and manufacturing of biomedical devices, i.e., grafts, sutures, implants, surgical sealant films, prosthetic devices, etc., in the industry using it as a raw material.

Fundamental aspects and recent developments in electropolishing

Abstract This paper is aimed at reviewing the fundamental aspects and recent developments in electropolishing process. The fundamental theories in the material removal mechanism of electropolishing process are introduced. Since electropolishing is a complicated process including electricity and chemical reaction, it is influenced by many process factors, such as current density, temperature, electrolyte types and workpiece rotation. There is still no available theory which can explain the electropolishing process well, especially when some recent developments were established, the material removal mechanism became more complicated in understanding. However, as the recent developments in the laser machining, additive manufacturing and biomedical device manufacturing, there is a need to use the electropolishing method to post-treat the surface obtained from these methods due to the high industrial requirements. The electropolishing method utilizes the electrochemical reaction between the anodic and cathodic electrodes, when the current is switched on with a DC/AC power supply, to remove the material from the surface of workpiece, hence, the polishing processes of various materials show quite different characteristics on the needed electrolyte types, current densities and so on. Therefore, the electropolishing of various materials is also reviewed in this work. The electropolishing has been not only used for the surface finishing of metal, but also for the passivation, deburring and pattern formation. Finally, a perspective in the development of electropolishing technique is presented to provide a reference for the further research.

Providing Antibacterial Activity to Poly(2-Hydroxy Ethyl Methacrylate) by Copolymerization with a Methacrylic Thiazolium Derivative.

Antimicrobial polymers and coatings are potent types of materials for fighting microbial infections, and as such, they have attracted increased attention in many fields. Here, a series of antimicrobial copolymers were prepared by radical copolymerization of 2-hydroxyethyl methacrylate (HEMA), which is widely employed in the manufacturing of biomedical devices, and the monomer 2-(4-methylthiazol-5-yl)ethyl methacrylate (MTA), which bears thiazole side groups susceptible to quaternization, to provide a positive charge. The copolymers were further quantitatively quaternized with either methyl or butyl iodide, as demonstrated by nuclear magnetic resonance (NMR) and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR). Then, the polycations were characterized by zeta potential measurements to evaluate their effective charge and by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) to evaluate their thermal properties. The ζ-potential study revealed that the quaternized copolymers with intermediate compositions present higher charges than the corresponding homopolymers. The cationic copolymers showed greater glass transition temperatures than poly(2-hydroxyethyl methacrylate) (PHEMA), with values higher than 100 °C, in particular those quaternized with methyl iodide. The TGA studies showed that the thermal stability of polycations varies with the composition, improving as the content of HEMA in the copolymer increases. Microbial assays targeting Gram-positive and Gram-negative bacteria confirmed that the incorporation of a low number of cationic units into PHEMA provides antimicrobial character with a minimum inhibitory concentration (MIC) of 128 µg mL−1. Remarkably, copolymers with MTA molar fractions higher than 0.50 exhibited MIC values as low as 8 µg mL−1.

Additive manufacturing of biomedical devices: an overview

Additive manufacturing (AM) especially using CAD-directed laser or electron beam melting (EBM) of metal or pre-alloyed powder beds is able to produce complex, porous mesh or foam biomedical devices. Engineered pore structures are able to accommodate bone stiffness and load-bearing stress levels especially for hip rod or stem implants. It is also possible to optimise attachment by bone ingrowth and even render implants ‘living’ bone support scaffolds by the infusion of collagen-based hydrogel matrices containing necessary cell types and a variety of transcription and signalling molecules or surgically extracted (femoral) trabecular matter for angiogenic and osteogenic induction. The proliferation of AM technologies in the U.S.A., China and India, including the installation of EBM systems for patient-specific porous implant fabrication in hospitals, especially in China, is discussed along with related clinical trials.

Antimicrobial Peptides in Biomedical Device Manufacturing.

Over the past decades the use of medical devices, such as catheters, artificial heart valves, prosthetic joints, and other implants, has grown significantly. Despite continuous improvements in device design, surgical procedures, and wound care, biomaterial-associated infections (BAI) are still a major problem in modern medicine. Conventional antibiotic treatment often fails due to the low levels of antibiotic at the site of infection. The presence of biofilms on the biomaterial and/or the multidrug-resistant phenotype of the bacteria further impair the efficacy of antibiotic treatment. Removal of the biomaterial is then the last option to control the infection. Clearly, there is a pressing need for alternative strategies to prevent and treat BAI. Synthetic antimicrobial peptides (AMPs) are considered promising candidates as they are active against a broad spectrum of (antibiotic-resistant) planktonic bacteria and biofilms. Moreover, bacteria are less likely to develop resistance to these rapidly-acting peptides. In this review we highlight the four main strategies, three of which applying AMPs, in biomedical device manufacturing to prevent BAI. The first involves modification of the physicochemical characteristics of the surface of implants. Immobilization of AMPs on surfaces of medical devices with a variety of chemical techniques is essential in the second strategy. The main disadvantage of these two strategies relates to the limited antibacterial effect in the tissue surrounding the implant. This limitation is addressed by the third strategy that releases AMPs from a coating in a controlled fashion. Lastly, AMPs can be integrated in the design and manufacturing of additively manufactured/3D-printed implants, owing to the physicochemical characteristics of the implant material and the versatile manufacturing technologies compatible with antimicrobials incorporation. These novel technologies utilizing AMPs will contribute to development of novel and safe antimicrobial medical devices, reducing complications and associated costs of device infection.

Evaluation of the permeability of silver nanoparticles in polymer films of sulfonated polystyrene-co-acrylic acid

Nanoparticulate materials exhibit interesting physicochemical properties due to its high surface area and reactivity. They are promising for application in the development of catalytic systems, electronic and photovoltaic devices, fuel cells, sensors, biomaterials, among others. Silver nanoparticles (AgNPs) are recognized by their biocidal action, which makes them attractive in the manufacture of biomedical devices, including skin patches with antimicrobial properties. However, there are very few studies on the permeation of nanoparticles in polymer films and tissues. In this works, we present the results of Ag+ ion and silver nanoparticles permeation studies in poly-[St-co-AA] and poly-[StS-co-AA] (StS=styrene sulfonated) membranes using electrochemical techniques. Polymeric films were characterized by spectroscopic technics and atomic force microscopy. Our findings demonstrated that the sulfonated copolymer in the medium is more permeable to the diffusion of AgNPs when compared to the non-sulfonated film. Regarding the Ag+ ion, the presence of the polymeric film in the electrodes, does not affect the E1/2 of the redox process Ag+/Ag0.

Effects of the Dynamic Tapping Process on the Biocompatibility of Ti-6Al-4V Alloy in Simulated Human Body Environment

The use of biomaterials depends on the high quality of the manufacturing and processing technology. Thus, the goal of this study is to contribute to the field of manufacturing of biomedical devices used in the human body. The forming and machining microtapping process (M3 thread and pitch 0.5 mm) in Ti-6Al-4V alloy was investigated. The design of experiments (DoE) was performed to identify the effects of factors (speed and type of process) on the thrust force, torque, and ultra-microhardness. The biocompatibility of the formed and machined thread surfaces was evaluated through potentiostatic polarization and electrochemical impedance tests. A simulated body fluid was used as the electrolyte. The experimental results showed that the rate of passivation of titanium alloy was highest for machined threads. Furthermore, the low level of speed (2 m/min) presented better surface finish and more complete fill rate of thread profile.

Surface Finishing of Strongly Passive Biomedical Materials, such as Nitinol, in Low- and Non-Acid Electrolytes

A process for surface finishing of biomedical alloys is described. For strongly passivating metals, electropolishing under direct current (DC) electric fields in a simple electrolyte can lead to a roughened surface. To remove the passive film, aggressive chemicals are added to the electrolyte, for example, hydrofluoric acid may be used to depassivate the surface.[1]A pulse/pulse reverse waveform can be used to electropolish passive materials, by tuning anodic pulses to control mass transport and current distribution, interspersed with cathodic pulses to depassivate the surface.[2]-,[3],[4],[5]Off-times inserted between the anodic and cathodic pulses facilitate replenishment of reacting species and removal of by-products and heat. The cathodic pulse eliminates the need for HF or other chemicals to remove the surface oxide. While the exact mechanism of depassivation is unknown at this stage, we speculate that the cathodic pulses remove the oxide either by direct electrochemical reduction or indirect chemical reduction, and restore the virgin metal surface prior to the next anodic pulse. The amplitude of the cathodic pulses required for depassivation is material specific, and appears to be based on the strength of the passive film.The inclusion of cathodic pulses and off-times suggests that the overall process would be slower than a conventional DC process, which is undesirable for industrial implementation. However, the maximum current density during the anodic pulse is higher than the DC limiting current density. Therefore, the overall removal rate of a pulsed process can rival or exceed that of a DC process despite a duty cycle that is less than 100%, while enjoying enhanced process performance.Studies in near-neutral aqueous solutions have demonstrated the feasibility of eliminating toxic solutions from manufacturing of biomedical devices. The best processing conditions to date for Nitinol in 17 w/w% H2SO4 has resulted in a final surface Ra of 0.19 µm. We have electropolished Ti-15Mo and Ti-Al-Nb alloys in 10 w/w% H2SO4 or 150 g/L Na2SO4to an Ra of 0.12 µm and 0.23 µm, respectively. We have done preliminary work on Ti-6Al-4V, achieving a near-mirror like surface finish.For electropolishing of stainless steels in an aqueous NaCl-NaNO3 electrolyte, a waveform sequence of short anodic pulses with interspersed cathodic pulses for 30 s followed by a waveform with long anodic pulses and interspersed cathodic pulses for 15 s has achieved a final Raof 0.026 µm (Figure 1: SS316 surface before and after FARADAYIC® Electropolishing). Finally, we have electropolished molybdenum to a mirror-like surface finish, and investigated on cobalt-chrome alloys and rhenium alloys.In summary, we have described a pulse reverse electropolishing process that may be applied to biomedical alloys using low viscosity aqueous electrolytes, devoid of aggressive chemicals for depassivating the surface. Consequently, the safety and chemical handling and disposal issues associated with pulse reverse electropolishing are minimized. In addition, the need for active chilling is minimized by the appropriate use of off-times and we anticipate that the process reproducibility and robustness are greatly enhanced. Acknowledgements: The authors acknowledge the financial support of Faraday corporate, NIH Grant No.1 R43 HL095216-01A1, DOE P.O. No. 594128 and DOE Contract No. DE-SC0004588.

Influence of operating parameters on surface properties of RF glow discharge oxygen plasma treated TiO2/PET film for biomedical application

In this paper, a thin transparent titania (TiO2) film was coated on the surface of flexible poly(ethylene terephthalate) (PET) film using the sol–gel method. The surface properties of the obtained TiO2/PET film were further improved by RF glow discharge oxygen plasma as a function of exposure time and discharge power. The changes in hydrophilicity of TiO2/PET films were analyzed by contact angle measurements and surface energy. The influence of plasma on the surface of the TiO2/PET films was analyzed by atomic force microscopy (AFM) as well as the change in chemical state and composition that were investigated by X-ray photo electron spectroscopy (XPS). The cytotoxicity of the TiO2/PET films was analyzed using human osteoblast cells and the bacterial eradication behaviors of TiO2/PET films were also evaluated against Staphylococcus bacteria. It was found that the surface roughness and incorporation of oxygen containing polar functional groups of the plasma treated TiO2/PET films increased substantially as compared to the untreated one. Moreover the increased concentration of Ti3+ on the surface of plasma treated TiO2/PET films was due to the transformation of chemical states (Ti4+→Ti3+). These morphological and chemical changes are responsible for enhanced hydrophilicity of the TiO2/PET films. Furthermore, the plasma treated TiO2/PET film exhibited no citotoxicity against osteoblast cells and antibacterial activity against Staphylococcus bacteria which can find application in manufacturing of biomedical devices.

Focus on sensors

Focus on sensors

A closer look at microabrasive blasting

This paper is aimed at reviewing the fundamental aspects and recent developments in electropolishing process. The fundamental theories in the material removal mechanism of electropolishing process are introduced. Since electropolishing is a complicated process including electricity and chemical reaction, it is influenced by many process factors, such as current density, temperature, electrolyte types and workpiece rotation. There is still no available theory which can explain the electropolishing process well, especially when some recent developments were established, the material removal mechanism became more complicated in understanding. However, as the recent developments in the laser machining, additive manufacturing and biomedical device manufacturing, there is a need to use the electropolishing method to post-treat the surface obtained from these methods due to the high industrial requirements. The electropolishing method utilizes the electrochemical reaction between the anodic and cathodic electrodes, when the current is switched on with a DC/AC power supply, to remove the material from the surface of workpiece, hence, the polishing processes of various materials show quite different characteristics on the needed electrolyte types, current densities and so on. Therefore, the electropolishing of various materials is also reviewed in this work. The electropolishing has been not only used for the surface finishing of metal, but also for the passivation, deburring and pattern formation. Finally, a perspective in the development of electropolishing technique is presented to provide a reference for the further research.

Characteristics of an Ultrafiltered Deionized Water System Used in the Manufacture of Implantable Biomedical Devices

The purpose of this paper is to demonstrate the characteristics of an ultrafiltered deionized water system used in the manufacture of biomedical devices. The water system was designed to reduce product concerns with respect to ionic contamination, organic contamination, and microbial contamination. The goal of the system was to produce high-purity deionized water that exceeded the requirements of USP pure water and meet the manufacturing requirements of electronic device assembly. This goal was achieved by using a compact design, select materials of construction, and robust pretreatment to reduce the burden to the ultrafiltration system. Continuous supply is delivered to all points of use through balanced pressures within the system and without a bulk storage tank. System maintenance is reduced to routine daily monitoring and sanitization once per month. Detailed descriptions of the system design, system operating conditions, and variable data are included to demonstrate system performance.