Bioinspired scaffold design using a custom Voronoi path generator for extrusion-based 3D printing.

Chronic low-grade systemic inflammation causes DNA damage in the lungs of mice

Idiopathic pulmonary fibrosis (IPF) is a restrictive fibrotic lung disease of uncertain etiology. Alveolar epithelial injury may be one of the inciting triggers in the pathogenesis of this disorder. We hypothesized that circulating antibodies to alveolar epithelial and endothelial cells may be involved in the pathogenesis of IPF. Antibodies to alveolar epithelial and endothelial cells were analyzed by indirect immunofluorescence using alveolar epithelial cells (A549) and human umbilical vein endothelial cells respectively. IgG and IgM antibodies in patients' serum were evaluated. Patterns of immunofluorescence, including membranous, cytoplasmic, and nuclear staining, were analyzed by fluorescence microscopy. The severity of immunofluorescence was divided into mild, moderate, and severe categories. Fifty-six patients (IPF = 28, non-IPF ILD = 9, non-ILD control = 19) were evaluated for antiepithelial antibodies, and 28 patients (IPF = 12, non-IPF ILD = 3, non-ILD control = 13) were studied for antiendothelial antibodies. Compared with control subjects, serum from IPF patients displayed significantly higher IgG binding to alveolar epithelial cells (P = 0.041) with a membranous pattern of immunofluorescence. However, there was no significant difference in immunofluorescence with IgG on endothelial cells (P = 0.165). In terms of IgM antibodies, there was no differential fluorescence observed for either epithelial or endothelial cells. There is evidence of increased IgG antibodies directed against alveolar epithelium in IPF. These antibodies may play a significant role in the pathogenesis of this fibrotic disorder. The findings of this study suggest further evaluation of the role of immune mediated alveolar epithelial injury in IPF.

Human epithelial (A549) cells exposed to hyperoxia die by cellular necrosis. In the current study, we demonstrated the involvement of apoptogenic factors in epithelial cell necrosis in response to hyperoxia, including the formation of the Fas-related death-inducing signaling complex and initiation of mitochondria-dependent apoptotic pathways. We showed increased activation of both Bid and Bax in A549 cells subjected to hyperoxia. Bax activation involved a Bid-assisted conformational change. We discovered that the response to hyperoxia in vivo predominantly involved the activation of the Bid/caspase-8 pathway without apparent increases in Bax expression. Disruption of the Bid pathway by gene deletion protected against cell death in vivo and in vitro. Likewise, inhibition of caspase-8 by Flip also protected against cell death. Taken together, we have demonstrated the involvement of apoptogenic factors in epithelial cell responses to hyperoxia, despite a final outcome of cellular necrosis. We have, for the first time, identified a predominant role for the caspase-8/Bid pathway in signaling associated with hyperoxic lung injury and cell death in vivo and in vitro.

Two types of additive manufacturing (AM) techniques, fused filament fabrication (FFF) and selective laser sintering (SLS), were employed to fabricate specimens from three widely used AM polymers: polylactic acid (PLA), acrylonitrile butadiene styrene (ABS), and polyamide (PA): the first two using FFF and PA using SLS. The single‐edge notch bending (SENB) test was employed to measure the mode‐I fracture toughnesses of bulk and AM specimens in three directions relative to the printing direction. Unlike their bulk counterparts, AM polymers exhibited anisotropic fracture toughness. The degree of anisotropy in FFF‐PLA was much larger than FFF‐ABS and SLS‐PA. The smallest fracture toughness value for each AM polymer was achieved along the transverse printing direction. Different AM techniques affect fracture toughness differently. For instance, FFF is shown to increase PLA's plastic deformation, while SLS reduces PA's ductility. The decrease in fracture toughness is consistently observed when transitioning from bulk polymers to AM ones, reaching as much as 75%. This study provides insights into the fracture toughness of AM parts made via popular plastics, which are crucial for designing structural parts using FFF and SLS processes.

PurposeFabrication of customized products in low volume through conventional manufacturing incurs a high cost, longer processing time and huge material waste. Hence, the concept of additive manufacturing (AM) comes into existence and fused deposition modelling (FDM), is at the forefront of researches related to polymer-based additive manufacturing. The purpose of this paper is to summarize the research works carried on the applications of FDM.Design/methodology/approachIn the present paper, an extensive review has been performed related to major application areas (such as a sensor, shielding, scaffolding, drug delivery devices, microfluidic devices, rapid tooling, four-dimensional printing, automotive and aerospace, prosthetics and orthosis, fashion and architecture) where FDM has been tested. Finally, a roadmap for future research work in the FDM application has been discussed. As an example for future research scope, a case study on the usage of FDM printed ABS-carbon black composite for solvent sensing is demonstrated.FindingsThe printability of composite filament through FDM enhanced its application range. Sensors developed using FDM incurs a low cost and produces a result comparable to those conventional techniques. EMI shielding manufactured by FDM is light and non-oxidative. Biodegradable and biocompatible scaffolds of complex shapes are possible to manufacture by FDM. Further, FDM enables the fabrication of on-demand and customized prosthetics and orthosis. Tooling time and cost involved in the manufacturing of low volume customized products are reduced by FDM based rapid tooling technique. Results of the solvent sensing case study indicate that three-dimensional printed conductive polymer composites can sense different solvents. The sensors with a lower thickness (0.6 mm) exhibit better sensitivity.Originality/valueThis paper outlines the capabilities of FDM and provides information to the user about the different applications possible with FDM.

The forkhead box (Fox) proteins are a growing family of transcription factors that have important roles in cellular proliferation and differentiation and in organ morphogenesis. The Fox family members hepatocyte nuclear factor (HNF)-3beta (Foxa2) and HNF-3/forkhead homolog (HFH)-8 (FREAC-1, Foxf1) are expressed in adult pulmonary epithelial and mesenchymal cells, respectively, but these cells display only low expression levels of the proliferation-specific HFH-11B gene (Trident, Foxm1b). The regulation of these Fox transcription factors in response to acute lung injury, however, has yet to be determined. We report here on the use of butylated hydroxytoluene (BHT)-mediated lung injury to demonstrate that HFH-11 protein and RNA levels were markedly increased throughout the period of lung repair. The maximum levels of HFH-11 were observed by day 2 following BHT injury when both bronchiolar and alveolar epithelial cells were undergoing extensive proliferation. Although BHT lung injury did not alter epithelial cell expression of HNF-3beta, a 65% reduction in HFH-8 mRNA levels was observed during the period of mesenchymal cell proliferation. HFH-8-expressing cells were colocalized with platelet endothelial cell adhesion molecule-1-positive alveolar endothelial cells and with alpha-smooth muscle actin-positive peribronchiolar smooth muscle cells.

The very first application in the Additive Manufacturing (AM) is the development of prototypes, that too by using plastic in fused deposition modeling (FDM) 3D printing processes, Stereolithography, SLS and others. Apart from printing ordinary shaped objects, Additive Manufacturing is also able to produce composites by using different materials on a single production platform. Continuous research and development has improved Additive manufacturing capability to develop various composite materials including fiber-reinforced composite, Biocomposite, Nanocomposites, Polymer matrix composites and Polymers. The primary purpose of this work is the literature-based study on FDM printed composite materials. For this purpose, the keyword “FDM Composites” is used in SCOPUS search and research papers from reputed publishers and Journals were identified and studied. Further, discussed the methods for the development of composite using FDM, and different composite materials with their types which can be printed by using FDM are discussed in a tabular form. It is learned that FDM provides an extraordinary chance to develop typical AM parts with the use of composite materials. Exploration, expansion and commercialization of AM materials are a significant extent of the study in the field of a composite at present.

Fused deposition modelling (FDM) is one of the most promising and widely used additive manufacturing (AM) technologies. FDM is commonly used to fabricate simple to complex 3D parts from polymeric materials. Different 3D-printed polymeric components manufactured using FDM technology exhibit various mechanical and load-bearing properties. They are utilized in various industries, particularly the medical industry, for load-bearing applications in bio-implants. Therefore, it is crucial to understand the mechanical characteristics, especially the fatigue behaviour, of these 3D-printed parts under cyclic loadings. This paper focuses on the dynamic behaviour of 3D-printed polymeric parts produced through the FDM process and under different loading modes. First, the FDM mechanism, the various polymeric materials used in FDM, and the effective FDM parameters are briefly introduced. Then, the paper comprehensively covers one of the most important mechanical characteristics of 3D-printed parts for load-bearing applications: their fatigue life under different printing conditions and cyclic loadings. The most influential factors on the fatigue behaviour of polymers include the type of polymeric material, surrounding environmental conditions, cyclic loading conditions, the type of testing specimen, and the FDM printing parameters (such as raster angle, infill density, nozzle diameter, and nozzle temperature). In addition to the anisotropic behaviour reported by various studies on 3D-printed parts using FDM, it has been concluded that the layered structure (with a large number of interfaces between the raster) and the presence of microholes are two factors that weaken the fatigue strength of 3D-printed structures compared to other fabrication processes. These conditions can be exacerbated by choosing inappropriate printing parameters, and often, the failure mechanism in 3D-printed parts fabricated with FDM is delamination.

Fuse Deposition Modeling (FDM) offer several advantages such as less expensive material, lack of expensive lasers and allows complex geometry to be built. However, FDM have limitations such as seam lines appear between layers and excess material residue, leading to surface roughness and poor finish. Ultrasound has been applied in various conventional machining process and shows good machined surface finish. However, from the literature review, it was found there is no investigation made on the application of ultrasound for Additive Manufacturing (AM) especially for FDM. This paper presents an adaptive approach to improve surface finish of FDM sample by applying ultrasonic vibration. The papers discuss the result of the surface finish of test piece printed via a desktop FDM system whereby an ultrasound device that was securely mounted onto the platform during printing process. Frequency that was used in the experiment is 11, 16 and 21 kHz with acrylonitrile butadiene styrene (ABS) material. Optical microscope with the aid of pro VIS software version 2.90 was used to measure the surface roughness of the four samples printed with a vibration in the above specified frequency. It was found that a 21 kHz frequency applied to the FDM process achieved the best surface finish due to less surface defects found and thickness had finer layers being produced. The results from this study could potentially be applied to other AM system such as the selective laser sintering, electron beam machining and stereolithography. The new data on effects of ultrasonic FDM technique and machining parameter for achieving improved surface finish has potential benefit to be used in various industries such as automotive, consumer, medical, sports, etc to produce prototypes or customized end used product or part. The data will benefit in term of product design and development elimination of manual post processing. Further study that could be done is to use different types of material such as polyactic acid (PLA) or composite material.

Additive manufacturing (AM) processes, such as Fused Filament Fabrication (FFF), enable the production of lightweight parts with high stiffness-to-weight ratios, making them highly suitable for a wide range of engineering applications. However, ensuring the mechanical reliability of these components, particularly for load-bearing purposes, requires systematic mechanical testing of well-designed specimens to asses their suitability. While the tensile properties of additively manufactured materials have been extensively studied, the compressive behavior of components produced via AM, particularly those made from thermoplastic materials, remains comparatively underexplored and insufficiently characterized in the existing body of research. Among these materials, polylactic acid (PLA)—a biodegradable thermoplastic derived from renewable resources—has gained prominence in AM applications. Recent studies have investigated the compression properties of PLA in reinforced materials; however, the focus has primarily been on solid, semi-solid, or porous specimens. These investigations largely overlook thin-walled structures, which are integral to weight-saving designs and commonly feature in topology-optimized structures. Understanding the mechanical behavior of monolayers, the fundamental building blocks of most AM components, is essential for accurately predicting the overall performance of multilayer structures. Monolayers represent the smallest, most basic structural elements of AM parts, and their properties directly influence the behavior of the final, more complex assemblies. Establishing a methodology that correlates monolayer properties with those of multilayer components could significantly streamline testing procedures. By performing mechanical tests on monolayers, instead of on more intricate multilayer specimens, manufacturers could reduce testing complexity and cost while accelerating the development process. The current literature reveals a gap in the design and analysis of thin-walled AM specimens, especially monolayers, under compressive loads. Specifically, the design of monolayer or thin-walled AM compression specimens without infill has not been thoroughly explored. This article addresses this gap by investigating the design and testing of AM monolayer compression specimens produced using FFF of PLA. Three distinct specimen geometries are considered—circular, helicoidal, and S-shaped—to evaluate their potential for understanding and predicting the compressive behavior of AM monolayer structures.

In the systemic circulation, neutrophil emigration into sites of acute inflammation is mediated through the leukocyte adhesion complex, CD11/CD18. ICAM-1 is an inducible endothelial ligand for CD11a/CD18 and CD11b/CD18. Streptococcus pneumoniae elicits neutrophil emigration through a CD18-independent mechanism whereas Escherichia coli endotoxin elicits emigration through a CD18-dependent mechanism in rabbit lungs. To determine whether ICAM-1 is up-modulated in the lung during CD18-independent and CD18-dependent emigration, ultrastructural immunogold-labeling studies were performed on BALB/c mice given airway instillates of S. pneumoniae or E. coli endotoxin. Ultrathin cryosections of frozen lung tissue were immunogold labeled with the mAb YN1/1.7.4 against the murine homologue of human ICAM-1. Gold particles on the plasma membranes of alveolar endothelial and epithelial cells were quantitated by transmission electron microscopy. Capillary endothelial ICAM-1 expression did not change during neutrophil emigration toward S. pneumoniae, a CD18-independent pathway in rabbits. In contrast, ICAM-1 expression increased 4.2-fold in response to E. coli endotoxin (known to elicit CD18-dependent emigration in mice), suggesting that the mechanism of adhesion may be regulated by the expression of endothelial rather than neutrophil adhesion molecules. Constitutive expression of ICAM-1 on alveolar epithelial cells was 22-fold greater than on capillary endothelium. Epithelial expression was mainly restricted to type I pneumocytes, whereas type II pneumocytes, the precursors of type I cells, expressed little or no ICAM-1. However, during pneumonia, type II but not type I pneumocytes showed increased ICAM-1 expression, suggesting that ICAM-1 expression represents an early differentiation even in response to epithelial injury.

Digital twin (DT) and additive manufacturing (AM) technologies are key enablers for smart manufacturing systems. DTs of AM systems are proposed in recent literature to provide additional analysis and monitoring capabilities to the physical AM processes. This work proposes a DT framework for real-time performance monitoring and anomaly detection in fused deposition modeling (FDM) AM process. The proposed DT framework can accommodate AM process measurement data to model the AM process as a cyber-physical system with continuous and discrete event dynamics, and allow for the development of various applications. A new performance metric is proposed for performance monitoring and a formal specification based anomaly detection method is proposed for AM processes. Implementation of the proposed DT on an off-the-shelf FDM printer and experimental results of anomaly detection and process monitoring are presented at the end.

Additive manufacturing (AM) of fiber-reinforced composites has garnered significant interest for its versatility in creating intricate parts and rapid prototyping. Short fiber-reinforced composites are typically fabricated through fused deposition modeling (FDM), but they possess several challenges including limited fiber volume fraction (Vf), low printing speed, and low throughput for industry scales. Composite-based additive manufacturing (CBAM) is a novel sheet lamination-based AM process, combining non-woven fabric reinforcement with thermoplastic materials to fabricate three-dimensional objects. CBAM offers notable advantages over FDM, including the potential for achieving higher Vf and faster production rates, making it a promising technology for further investigation in composite manufacturing. This paper investigates the microstructural characteristics and porosity analyses of non-woven carbon fabric reinforced nylon composites (CF-PA12) manufactured by CBAM and FDM. Test coupons were fabricated in flatwise and edgewise printing orientations. CBAM flatwise specimens were less porous than edgewise specimens attributed to the comparatively higher number of sheets in edgewise orientation. This study highlights the microstructural characteristics of mechanical test specimens prepared using CBAM and FDM. It reveals that CBAM specimens exhibit a higher Vf, lower porosity, and smaller, more randomly distributed closed pores compared to FDM specimens, which enhance its material integrity and performance, offering a foundation for further development in composite AM technology.

The concept of 3D printing also known as Additive Manufacturing (AM) is gaining huge importance from industrialists as well as researchers. Fused Filament Fabrication (FFF) is a major share holder of AM in the present market, which uses polymer in the form of filament to be used as a raw material for development of either prototype or functional models. The creation of any complex model can be easily fabricated by FFF. The model to be printed is first developed in any CAD form and then converted to .stl file format, which is later sliced and then added as an input to the 3D printer. The option of using AM is opening a wide way, for enhancement in design properties and quick printing. There remains a certain constraint with usage of these polymers alone in attainment of required properties. Therefore, the need for enhancement of properties of fabricated parts is of much necessary, which could be possible by addition of filler material. Polymer alone would not be able to provide required mechanical properties therefore the filler material either in the form of macro or micro particles or even in the form of nano particles is used to enhance the properties. Several researchers have tried various combination of filler material with the matrix for increase in specified properties. This chapter provides an insight towards FFF and its necessity, discusses the various polymer composites used in FFF, mechanical and tribological behaviour of polymer composites with variety of reinforcement addition and its potential applications and scope of FFF in near future.

Additive manufacturing (AM) possesses a transformative potential to revolutionize personalized medicine fabrication. Fused filament fabrication (FFF), an advanced AM technique, enables the development of tailored medicines with customizable dosages and controlled release properties. Nevertheless, filament prerequisites impose material limitations and present considerable challenges, necessitating a comprehensive evaluation of mechanical, rheological, and thermal characteristics to circumvent complications during the FFF process. Droplet deposition modeling (DDM), an innovative AM approach derived from injection molding (IM) technology, processes granulate feedstock to facilitate the production of personalized medicines. This study delves into the effects of FFF, DDM, and IM techniques on the release profiles of Hydrochlorothiazide, a widely employed drug for hypertension and edema treatment. By varying infill density, the investigation assesses the manufactured tablets using DDM and FFF methods. Our findings show that tablets made with FFF and DDM with identical infill densities had distinct microstructures, resulting in variable drug release profiles. Decreasing the infill densities resulted in higher sample porosity, leading to an accelerated drug release rate. A comparative analysis of drug release profiles from DDM and IM fabricated tablets demonstrated notable differences, despite DDM's origins in injection molding technology. This comprehensive study underscores the significance of not only infill densities but also the choice of manufacturing technique, as both factors can profoundly influence drug release profiles. By shedding light on these considerations, the research contributes to the ongoing advancement of personalized medicine through additive manufacturing technologies.