Biomimicking Atherosclerotic Vessels: A Relevant and (Yet) Sub-Explored Topic.

Atherosclerosis represents the etiologic source of several cardiovascular events, including myocardial infarction, cerebrovascular accidents, and peripheral artery disease, which remain the leading cause of mortality in the world. Numerous strategies are being delineated to revert the non-optimal projections of the World Health Organization, by both designing new diagnostic and therapeutic approaches or improving the interventional procedures performed by physicians. Deeply understanding the pathological process of atherosclerosis is, therefore, mandatory to accomplish improved results in these trials. Due to their availability, reproducibility, low expensiveness, and rapid production, biomimicking physical models are preferred over animal experimentation because they can overcome some limitations, mainly related to replicability and ethical issues. Their capability to represent any atherosclerotic stage and/or plaque type makes them valuable tools to investigate hemodynamical, pharmacodynamical, and biomechanical behaviors, as well as to optimize imaging systems and, thus, obtain meaningful prospects to improve the efficacy and effectiveness of treatment on a patient-specific basis. However, the broadness of possible applications in which these biomodels can be used is associated with a wide range of tissue-mimicking materials that are selected depending on the final purpose of the model and, consequently, prioritizing some materials' properties over others. This review aims to summarize the progress in fabricating biomimicking atherosclerotic models, mainly focusing on using materials according to the intended application.

Preprocedural Planning of Left Atrial Appendage Occlusion: A Review of the Use of Additive Manufacturing.

Stroke is a significant public health problem, with non-valvular atrial fibrillation (NVAF) being one of its main causes. This cardiovascular arrhythmia predisposes to the production of intracardiac thrombi, mostly formed in the left atrial appendage (LAA). When there are contraindications to treatment with oral anticoagulants, another therapeutic option to reduce the possibility of thrombus formation in the LAA is the implantation of an occlusion device by cardiac catheterization. The effectiveness of LAA occlusion is dependent on accurate preprocedural device sizing and proper device positioning at the LAA ostium, to ensure sufficient device anchoring and avoid peri-device leaks. Additive manufacturing, commonly known as three-dimensional printing (3DP), of LAA models is beginning to emerge in the scientific literature to address these challenges through procedural simulation. This review aims at clarifying the impact of 3DP on preprocedural planning of LAA occlusion, specifically in the training of cardiac surgeons and in the assessment of the perfect adjustment between the LAA and the biomedical implant.

Ultrathin materials for wide bandwidth laser ultrasound generation: titanium dioxide nanoparticle films with adsorbed dye.

Materials that convert the energy of a laser pulse into heat can generate a photoacoustic wave through thermoelastic expansion with characteristics suitable for improved sensing, imaging, or biological membrane permeation. The present work involves the production and characterization of materials composed of an ultrathin layer of titanium dioxide (<5 µm), where a strong absorber molecule capable of very efficiently converting light into heat (5,10,15,20-tetrakis(4-sulfonylphenyl)porphyrin manganese(iii) acetate) is adsorbed. The influence of the thickness of the TiO2 layer and the duration of the laser pulse on the generation of photoacoustic waves was studied. Strong absorption in a thin layer enables bandwidths of ∼130 MHz at -6 dB with nanosecond pulse laser excitation. Bandwidths of ∼150 MHz at -6 dB were measured with picosecond pulse laser excitation. Absolute pressures reaching 0.9 MPa under very low energy fluences of 10 mJ cm-2 enabled steep stress gradients of 0.19 MPa ns-1. A wide bandwidth is achieved and upper high-frequency limits of ∼170 MHz (at -6 dB) are reached by combining short laser pulses and ultrathin absorbing layers.

Understanding Atherosclerosis Pathophysiology: Can Additive Manufacturing Be Helpful?

Atherosclerosis is one of the leading causes of death worldwide. Although this subject arouses much interest, there are limitations associated with the biomechanical investigation done in atherosclerotic tissues, namely the unstandardized tests for the mechanical characterization of these tissues and the inherent non-consensual results obtained. The variability of tests and typologies of samples hampers direct comparisons between results and hinders the complete understanding of the pathologic process involved in atherosclerosis development and progression. Therefore, a consensual and definitive evaluation of the mechanical properties of healthy and atherosclerotic blood vessels would allow the production of physical biomodels that could be used for surgeons' training and personalized surgical planning. Additive manufacturing (AM), commonly known as 3D printing, has attracted significant attention due to the potential to fabricate biomodels rapidly. However, the existing literature regarding 3D-printed atherosclerotic vascular models is still very limited. Consequently, this review intends to present the atherosclerosis disease and the consequences of this pathology, discuss the mechanical characterization of atherosclerotic vessels/plaques, and introduce AM as a potential strategy to increase the understanding of atherosclerosis treatment and pathophysiology.

Indirect Additive Manufacturing: A Valid Approach to Modulate Sorption/Release Profile of Molecules from Chitosan Hydrogels.

This work studied the influence of hydrogel's physical properties (geometry and hierarchical roughness) on the in vitro sorption/release profiles of molecules. To achieve this goal, chitosan (CS) solutions were cast in 3D-printed (3DP) molds presenting intricate shapes (cubic and half-spherical with/without macro surface roughness) and further immersed in alkaline solutions of NaOH and NaCl. The resulting physically crosslinked hydrogels were mechanically stable in aqueous environments and successfully presented the shapes and geometries imparted by the 3DP molds. Sorption and release profiles were evaluated using methyl orange (MO) and paracetamol (PMOL) as model molecules, respectively. Results revealed that distinct MO sorption/PMOL release profiles were obtained according to the sample's shape and presence/absence of hierarchical roughness. MO sorption capacity of CS samples presented both dependencies of hierarchical surface and geometry parameters. Hence, cubic samples without a hierarchical surface presented the highest (up to 1.2 × greater) dye removal capacity. Moreover, PMOL release measurements were more dependent on the surface area of hydrogels, where semi-spherical samples with hierarchical roughness presented the fastest (~1.13 × faster) drug delivery profiles. This work demonstrates that indirect 3DP (via fused filament fabrication (FFF) technology) could be a simple strategy to obtain hydrogels with distinct sorption/release profiles.

Co-W Barrier Layers for Metallization of Copper Interconnects: Thermal Performance Analysis.

The back-end-of-line (BEOL) copper interconnect structure has been subjected to downscaling for the last two decades, while the materials used for conforming and assuring its physical integrity during processing have faced significant obstacles as the single-digit nanometer process node is implemented. In particular, the diffusion barrier layer system comprised of Ta/TaN has faced major constraints when it comes to the electrical performance of the smaller Cu lines, and thus alternative formulations have been investigated in recent years, such as Ru-Ta or Co-W alloys. In this work, we assess how PVD (physical vapor deposition) deposited equimolar Co-W films perform when exposed to different vacuum annealing temperatures and how these films compare with the Ta adhesion layer used for Cu seeding in terms of dewetting resistance. The stacks were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) coupled with energy dispersive X-ray spectroscopy (EDX) mapping. The Cu film at the surface of the Cu/Co-W system exhibited grain growth starting at 300 °C, with the formation of abnormally large Cu grains starting at 450 °C. Sheet resistance reached a minimum value of 7.07 × 10-6 Ω/sq for the Cu/Co-W stack and 6.03 × 10-6 Ω/sq for the Cu/Ta stack, both for the samples annealed at 450 °C.

3D Printing for Cartilage Replacement: A Preliminary Study to Explore New Polymers.

The use of additive manufacturing technologies for biomedical applications must begin with the knowledge of the material to be used, by envisaging a very specific application rather than a more general aim. In this work, the preliminary study was focused on considering the cartilaginous tissue. This biological tissue exhibits different characteristics, such as thickness and mechanical properties, depending on its specific function in the body. Due to the lack of vascularization, cartilage is a supporting connective tissue with limited capacity for recovery and regeneration. For this reason, any approach, whether to repair/regenerate or as a total replacement, needs to fulfill the adequate mechanical and chemical properties of the surrounding native cartilage to be successful. This work aims to explore the possibility of using new polymers for cartilage total replacement approaches with polymeric materials processed with the specific 3D printing technique of fused filament fabrication (FFF). The materials studied were Nylon® 12 (PA12), already described for this purpose, and LAY-FOMM® 60 (FOMM). FOMM has not been described in the literature for biomedical purposes. Therefore, the chemical, thermal, swelling capacity, and mechanical properties of the filaments were thoroughly characterized to better understand the structure-properties-application relationships of this new polymer. In addition, as the FFF technology is temperature based, the properties were also evaluated in the printed specimens. Due to the envisaged application, the specimens were also characterized in the wet state. When comparing the obtained results with the properties of native cartilage, it was possible to conclude that: (i) PA12 exhibits low swelling capacity, while FOMM, in its dry and wet forms, has a higher swelling capacity, closer to that of native cartilage; (ii) the mechanical properties of the polymeric materials, especially PA12, are higher than those of native cartilage; and (iii) from the mechanical properties evaluated by ultra-micro hardness tests, the values for FOMM indicate that this material could be a good alternative for cartilage replacement in older patients. This preliminary study, essentially devoted to expanding the frontiers of the current state of the art of new polymeric materials, provides valuable indications for future work targeting the envisaged applications.

3D Printing of Polymeric Bioresorbable Stents: A Strategy to Improve Both Cellular Compatibility and Mechanical Properties.

One of the leading causes of death is cardiovascular disease, and the most common cardiovascular disease is coronary artery disease. Percutaneous coronary intervention and vascular stents have emerged as a solution to treat coronary artery disease. Nowadays, several types of vascular stents share the same purpose: to reduce the percentage of restenosis, thrombosis, and neointimal hyperplasia and supply mechanical support to the blood vessels. Despite the numerous efforts to create an ideal stent, there is no coronary stent that simultaneously presents the appropriate cellular compatibility and mechanical properties to avoid stent collapse and failure. One of the emerging approaches to solve these problems is improving the mechanical performance of polymeric bioresorbable stents produced through additive manufacturing. Although there have been numerous studies in this field, normalized control parameters for 3D-printed polymeric vascular stents fabrication are absent. The present paper aims to present an overview of the current types of stents and the main polymeric materials used to fabricate the bioresorbable vascular stents. Furthermore, a detailed description of the printing parameters' influence on the mechanical performance and degradation profile of polymeric bioresorbable stents is presented.

Fabrication of 3D scaffolds based on fully biobased unsaturated polyester resins by microstereo-lithography.

Additive Manufacturing (AM) technologies are an effective route to fabricate tailor made scaffolds for tissue engineering (TE) and regenerative medicine, with microstereo-lithography (µSLA) being one of the most promising techniques to produce high quality 3D structures. Here, we report the crosslinking studies of fully biobased unsaturated polyesters (UPs) with 2-hydroxyethyl methacrylate (HEMA) as the unsaturated monomer (UM), using thermal and µSLA crosslinking processes. The resulting resins were fully characterized in terms of their thermal and mechanical properties. Determination of gel content, water contact angle, topography and morphology analysis by atomic force microscopy and scanning electron microscopy were also performed. The results show that the developed UP resins (UPRs) have promising properties for µSLA.In vitrocytotoxicity assays performed with 3T3-L1 cell lines showed that the untreated scaffolds exhibited a maximum cellular viability around 60%, which was attributed to the acidic nature of the UPRs. The treatment of the UPRs and scaffolds with ethanol (EtOH) improved the cellular viability to 100%. The data presented in this manuscript contribute to improve the performance of biobased UPs in AM.

Modification of the Cavity of Plastic Injection Molds: A Brief Review of Materials and Influence on the Cooling Rates.

In the 21st century, a great percentage of the plastic industry production is associated with both injection molding and extrusion processes. Manufactured plastic components/parts are used in several industry sectors, where the automotive and aeronautic stand out. In the injection process cycle, the cooling step represents 60% to 80% of the total injection process time, and it is used to estimate the production capabilities and costs. Therefore, efforts have been focused on obtaining more efficient cooling systems, seeking the best relationship between the shape, the quantity, and the distribution of the cooling channels into the injection molds. Concomitantly, the surface coating of the mold cavity also assumes great importance as it can provide increased hardness and a more straightforward demolding process. These aspects contribute to the decrease of rejected parts due to surface defects. However, the effect of the coated cavity on the heat transfer and, consequently, on the time of the injection cycle is not often addressed. This paper reviews the effects of the materials and surface coatings of molds cavity on the filling and cooling of the injection molding cycle. It shows how the design of cooling channels affects the cooling rates and warpage for molded parts. It also addresses how the surface coating influence the mold filling patterns and mold cooling. This review shows, more specifically, the influence of the coating process on the cooling step of the injection cycle and, consequently, in the productivity of the process.

Sandwich Multi-Material 3D-Printed Polymers: Influence of Aging on the Impact and Flexure Resistances.

With the advances in new materials, equipment, and processes, additive manufacturing (AM) has gained increased importance for producing the final parts that are used in several industrial areas, such as automotive, aeronautics, and health. The constant development of 3D-printing equipment allows for printing multi-material systems as sandwich specimens using, for example, double-nozzle configurations. The present study aimed to compare the mechanical behavior of multi-material specimens that were produced using a double-nozzle 3D printer. The materials that were included in this study were the copolymer acrylonitrile-butadiene-styrene (ABS), high-impact polystyrene (HIPS), poly(methyl methacrylate) (PMMA), and thermoplastic polyurethane (TPU). The configuration of the sandwich structures consisted of a core of TPU and the outer skins made of one of the other three materials. The mechanical behavior was evaluated through three-point bending (3PB) and transverse impact tests and compared with mono-material printed specimens. The effect of aging in artificial saliva was evaluated for all the processed materials. The main conclusion of this study was that the aging process did not significantly alter the mechanical properties for mono-materials, except for PMMA, where the maximum flexural stress decreased. In the sandwich structures, the TPU core had a softening effect, inducing a significant increase in the resilience and resistance to transverse impact. The obtained results are quite promising for applications in biomedical devices, such as protective mouthguards or teeth aligners. In these specific applications, the changes in the mechanical properties with time and with the contact of saliva assume particular importance.

Pyomelanin Synthesis in Alternaria alternata Inhibits DHN-Melanin Synthesis and Decreases Cell Wall Chitin Content and Thickness.

The genus Alternaria includes several of fungi that are darkly pigmented by DHN-melanin. These are pathogenic to plants but are also associated with human respiratory allergic diseases and with serious infections in immunocompromised individuals. The present work focuses on the alterations of the composition and structure of the hyphal cell wall of Alternaria alternata occuring under the catabolism of L-tyrosine and L-phenylalanine when cultured in minimal salt medium (MM). Under these growing conditions, we observed the released of a brown pigment into the culture medium. FTIR analysis demonstrates that the produced pigment is chemically identical to the pigment released when the fungus is grown in MM with homogentisate acid (HGA), the intermediate of pyomelanin, confirming that this pigment is pyomelanin. In contrast to other fungi that also synthesize pyomelanin under tyrosine metabolism, A. alternata inhibits DHN-melanin cell wall accumulation when pyomelanin is produced, and this is associated with reduced chitin cell wall content. When A. alternata is grown in MM containing L-phenylalanine, a L-tyrosine percursor, pyomelanin is synthesized but only at trace concentrations and A. alternata mycelia display an albino-like phenotype since DHN-melanin accumulation is inhibited. CmrA, the transcription regulator for the genes coding for the DHN-melanin pathway, is involved in the down-regulation of DHN-melanin synthesis when pyomelanin is being synthetized, since the CMRA gene and genes of the enzymes involved in DHN-melanin synthesis pathway showed a decreased expression. Other amino acids do not trigger pyomelanin synthesis and DHN-melanin accumulation in the cell wall is not affected. Transmission and scanning electron microscopy show that the cell wall structure and surface decorations are altered in L-tyrosine- and L-phenylalanine-grown fungi, depending on the pigment produced. In summary, growth in presence of L-tyrosine and L-phenylalanine leads to pigmentation and cell wall changes, which could be relevant to infection conditions where these amino acids are expected to be available.

Electroactive Polymers Obtained by Conventional and Non-Conventional Technologies.

Electroactive polymers (EAPs), materials that present size/shape alteration in response to an electrical stimulus, are currently being explored regarding advanced smart devices, namely robotics, valves, soft actuators, artificial muscles, and electromechanical sensors. They are generally prepared through conventional techniques (e.g., solvent casting and free-radical polymerization). However, non-conventional processes such as those included in additive manufacturing (AM) are emerging as a novel approach to tune and enhance the electromechanical properties of EAPs to expand the scope of areas for this class of electro-responsive material. This review aims to summarize the published work (from the last five years) in developing EAPs either by conventional or non-conventional polymer processing approaches. The technology behind each processing technique is discussed as well as the main mechanism behind the electromechanical response. The most common polymer-based materials used in the design of current EAPs are reviewed. Therefore, the main conclusions and future trends regarding EAPs obtained by conventional and non-conventional technologies are also given.

Influence of Build Orientation, Geometry and Artificial Saliva Aging on the Mechanical Properties of 3D Printed Poly(ε-caprolactone).

Additive manufacturing of polymers has evolved from rapid prototyping to the production of functional components/parts with applications in distinct areas, ranging from health to aeronautics. The possibility of producing complex customized geometries with less environmental impact is one of the critical factors that leveraged the exponential growth of this processing technology. Among the several processing parameters that influence the properties of the parts, the geometry (shape factor) is amid less reported. Considering the geometric complexity of the mouth, including the uniqueness of each teething, this study can contribute to a better understanding of the performance of polymeric devices used in the oral environment for preventive, restorative, and regenerative therapies. Thus, this work aims to evaluate 3D printed poly(ε-caprolactone) mechanical properties with different build orientations and geometries. Longitudinal and transversal toolpaths produced specimens with parallelepiped and tubular geometry. Moreover, as it is intended to develop devices for dentistry, the influence of artificial saliva on mechanical properties was determined. The research concluded that the best mechanical properties are obtained for parallelepiped geometry with a longitudinal impression and that aging in artificial saliva negatively influences all the mechanical properties evaluated in this study.

Using amyloid autofluorescence as a biomarker for lysozyme aggregation inhibition.

The assembly of proteins into amyloidogenic aggregates underlies the onset and symptoms of several pathologies, including Alzheimer's disease, Parkinson's disease and type II diabetes. Among the efforts for fighting these diseases, there is a great demand for developing novel, fast and reliable methods for in vitro screening of new drugs that may suppress or reverse amyloidogenesis. Recent studies unravelled a progressive increase in a blue autofluorescence upon amyloid formation originated from many different proteins, including the peptide amyloid-ß, lysozyme or insulin. Herein, we propose a drug screening method using this property, avoiding the use of external probe dyes. We demonstrate that the inhibition of lysozyme amyloid formation by means of two known inhibitors, tartrazine and amaranth, can be monitored based on the autofluorescence of lysozyme amyloid aggregates. Our results show that amyloid luminescence is an intrinsic property that can be potentially applied in a screening assay, allowing the ranking of drug efficiency. The assays demonstrated here are fast to perform and suitable for scaling using microplate assays, configuring a new sensitive and economically feasible method.

Semi-interpenetrating chitosan/ionic liquid polymer networks as electro-responsive biomaterials for potential wound dressings and iontophoretic applications.

In this work, electro-responsive chitosan/ionic liquid-based hydrogels were synthetized for the first time, envisaging the development of iontophoretic biomaterials for the controlled release/permeation of charged biomolecules. The main goal was to enhance and tune the physicochemical, mechanical, electro-responsive, and haemostatic properties of chitosan-based biomaterials to obtain multi-stimuli responsive (responsive to electrical current, ionic strength, and pH) and mechanically stable hydrogels. To accomplish this objective, polycationic semi-interpenetrating copolymer networks (semi-IPN) were prepared by combining chitosan (CS) and ionic liquid-based polymers and copolymers, namely poly(1-butyl-3-vinylimidazolium chloride) (poly(BVImCl)) and poly(2-hydroxymethyl methacrylate-co-1-butyl-3-vinylimidazolium chloride) (poly(HEMA-co-BVImCl)). Results show that prepared semi-IPNs presented high mechanical stability and were positively charged over a broad pH range, including basic pH. Semi-IPNs also presented faster permeation and release rates of lidocaine hydrochloride (LH), under external electrical stimulus (0.56 mA/cm2) in aqueous media at 32 °C. The kinetic release constants and the LH diffusion coefficients measured under electrical stimulus were ~1.5 and > 2.7 times higher for those measured for passive release. Finally, both semi-IPNs were non-haemolytic (haemolytic index ≤0.2%) and showed strong haemostatic activity (blood clotting index of ~12 ± 1%). Altogether, these results show that the prepared polycationic semi-IPN hydrogels presented advantageous mechanical, responsive and biological properties that enable them to be potentially employed for the design of new, safer, and advanced stimuli-responsive biomaterials for several biomedical applications such as haemostatic and wound healing dressings and iontophoretic patches.

Imaging of photoacoustic-mediated permeabilization of giant unilamellar vesicles (GUVs).

Target delivery of large foreign materials to cells requires transient permeabilization of the cell membrane without toxicity. Giant unilamellar vesicles (GUVs) mimic the phospholipid bilayer of the cell membrane and are also useful drug delivery vehicles. Controlled increase of the permeability of GUVs is a delicate balance between sufficient perturbation for the delivery of the GUV contents and damage to the vesicles. Here we show that photoacoustic waves can promote the release of FITC-dextran or GFP from GUVs without damage. Real-time interferometric imaging offers the first movies of photoacoustic wave propagation and interaction with GUVs. The photoacoustic waves are seen as mostly compressive half-cycle pulses with peak pressures of ~ 1 MPa and spatial extent FWHM ~ 36 µm. At a repetition rate of 10 Hz, they enable the release of 25% of the FITC-dextran content of GUVs in 15 min. Such photoacoustic waves may enable non-invasive targeted release of GUVs and cell transfection over large volumes of tissues in just a few minutes.

Polymeric Coatings with Antimicrobial Activity: A Short Review.

The actual situation of microorganisms resistant to antibiotics and pandemics caused by a virus makes research in the area of antimicrobial and antiviral materials and surfaces more urgent than ever. Several strategies can be pursued to attain such properties using different classes of materials. This review focuses on polymeric materials that are applied as coatings onto pre-existing components/parts mainly to inhibit microbial activity, but polymer surfaces with biocidal properties can be reported. Among the several approaches that can be done when addressing polymeric coatings, this review will be divided in two: antimicrobial activities due to the topographic cues, and one based on the chemistry of the surface. Some future perspectives on this topic will be given together with the conclusions of the literature survey.

3D printing goes greener: Study of the properties of post-consumer recycled polymers for the manufacturing of engineering components.

This study concerns the evaluation of several properties/characteristics of 3D printed poly(lactic acid) (PLA) polymer and acrylonitrile-butadienestyrene (ABS) copolymer, recycled from food packages and car dashboards, respectively. The aim is to evaluate the potential of recycled polymers that are recovered from solid polymer waste (SPW) to be reused for functional components/parts for add-value applications. The study compared the performance of the recycled material with the obtained from the 3D printing of virgin polymer. The characterization was made considering the chemical, thermal and mechanical properties as well as surface roughness and wettability. Although the thermal characterization did not indicate significant variations between recycled and virgin material, the mechanical recycling process induced some chain scission in PLA. Consequently, the semi-crystalline polymer revealed losses of 33% both in tensile stress and flexural strength. On the contrary, recycled ABS did not show changes in the mechanical properties of the printed specimens. Both recycled polymers produced smoother surfaces with a decrease of the mean surface roughness between 55% and 65%. Considering the properties required by manufacturers of food containers and car dashboards, this study indicates that recycled materials can be reused for the same applications.

Effect of Post-Cure on the Static and Viscoelastic Properties of a Polyester Resin.

This work intends to study the effect of the curing parameters on the mechanical properties of a polyester resin without a complete curing reaction process. For this purpose, cures at room temperature, 40 °C, and 60 °C, and post-cures at 40 °C and 60 °C, with different exposure times, were considered. Three-point bending tests were performed to assess the bending properties and both stress relaxation and creep behavior. The degree of crosslinking was estimated by evaluating the C = C ester bond, by Fourier infrared spectroscopy and complemented with the thermal characterization made by differential scanning calorimetry. The results showed that higher curing temperatures are preferable to methods involving curing and post-curing, which can be confirmed by the higher degree of conversion of unsaturated ester bonds at 60 °C. Compared to the resin cured at room temperature, the bending strength increased by 36.5% at 40 °C and 88.6% at 60 °C. A similar effect was observed for bending stiffness. In terms of stress relaxation and creep strain, the lowest values were obtained for samples cured at 60 °C.