Engineered Biomaterials: Design, Modeling, Synthesis, Characterization and Applications

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: closed (15 November 2022) | Viewed by 46528

Special Issue Editors


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Guest Editor
Center for Midstream Management and Science, Lamar University, Beaumont, TX, USA
Interests: nanomaterials; nanobiotechnology; bioprocessing; biosynthesis; microalgae; bioreactors; bio-applications; microwave synthesis; water treatment; wastewater treatment

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Guest Editor
Post Doctoral Fellow, Howard University, Washington, DC, United States
Interests: biomaterials; nanomaterials; biofouling materials; protein–surface interaction; modeling and simulation

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Special Issue Information

Dear Colleagues,

The last two decades have witnessed an exponential growth in cutting-edge research in the field of engineered biomaterials. The diversified use of these valuable biomaterials, either at the nanoscale, microscale, or macroscale, ranges from drug-delivery agents, imaging and detection nanoshuttles in cancer research and therapy, and implants, to name a few. As the field expands, the production and characterization of various bioactive structures possessing unique properties have become extremely important. Multiscale simulations are being used as an important tool to design and investigate biomaterials due to the rapid development of computational algorithms and resources. Theoretical analysis and computational simulations have already been proven to be powerful in studying the properties of such biomaterials along with their interaction with biological systems. Therefore, a combined research approach consisting of experiments, theoretical analysis, and computational simulations are of paramount importance to acquire new knowledge in the area of biomaterials and accelerate the emergence of innovative and efficient bio-applications.

To this end, we extend this invitation to submit innovative research articles and reviews on subjects pertaining to engineered biomaterials, structures or particles, design or modelling, production methods, characterization, and demonstrations of bio-applications.

Dr. Ashiqur Rahman
Dr. Md Symon Jahan Sajib
Dr. Si Amar Dahoumane
Guest Editors

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Published Papers (11 papers)

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Research

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16 pages, 3835 KiB  
Article
A Novel 3D Printing Particulate Manufacturing Technology for Encapsulation of Protein Therapeutics: Sprayed Multi Adsorbed-Droplet Reposing Technology (SMART)
by Niloofar Heshmati Aghda, Yu Zhang, Jiawei Wang, Anqi Lu, Amit Raviraj Pillai and Mohammed Maniruzzaman
Bioengineering 2022, 9(11), 653; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9110653 - 05 Nov 2022
Cited by 6 | Viewed by 2489
Abstract
Recently, various innovative technologies have been developed for the enhanced delivery of biologics as attractive formulation targets including polymeric micro and nanoparticles. Combined with personalized medicine, this area can offer a great opportunity for the improvement of therapeutics efficiency and the treatment outcome. [...] Read more.
Recently, various innovative technologies have been developed for the enhanced delivery of biologics as attractive formulation targets including polymeric micro and nanoparticles. Combined with personalized medicine, this area can offer a great opportunity for the improvement of therapeutics efficiency and the treatment outcome. Herein, a novel manufacturing method has been introduced to produce protein-loaded chitosan particles with controlled size. This method is based on an additive manufacturing technology that allows for the designing and production of personalized particulate based therapeutic formulations with a precise control over the shape, size, and potentially the geometry. Sprayed multi adsorbed-droplet reposing technology (SMART) consists of the high-pressure extrusion of an ink with a well determined composition using a pneumatic 3D bioprinting approach and flash freezing the extrudate at the printing bed, optionally followed by freeze drying. In the present study, we attempted to manufacture trypsin-loaded chitosan particles using SMART. The ink and products were thoroughly characterized by dynamic light scattering, rheometer, Scanning Electron Microscopy (SEM), and Fourier Transform Infra-Red (FTIR) and Circular Dichroism (CD) spectroscopy. These characterizations confirmed the shape morphology as well as the protein integrity over the process. Further, the effect of various factors on the production were investigated. Our results showed that the concentration of the carrier, chitosan, and the lyoprotectant concentration as well as the extrusion pressure have a significant effect on the particle size. According to CD spectra, SMART ensured Trypsin’s secondary structure remained intact regardless of the ink composition and pressure. However, our study revealed that the presence of 5% (w/v) lyoprotectant is essential to maintain the trypsin’s proteolytic activity. This study demonstrates, for the first time, the viability of SMART as a single-step efficient process to produce biologics-based stable formulations with a precise control over the particulate morphology which can further be expanded across numerous therapeutic modalities including vaccines and cell/gene therapies. Full article
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14 pages, 3507 KiB  
Article
Development of a CT-Compatible, Anthropomorphic Skull and Brain Phantom for Neurosurgical Planning, Training, and Simulation
by Marco Lai, Simon Skyrman, Flip Kor, Robert Homan, Victor Gabriel El-Hajj, Drazenko Babic, Erik Edström, Adrian Elmi-Terander, Benno H. W. Hendriks and Peter H. N. de With
Bioengineering 2022, 9(10), 537; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9100537 - 09 Oct 2022
Cited by 2 | Viewed by 1843
Abstract
Background: Neurosurgical procedures are complex and require years of training and experience. Traditional training on human cadavers is expensive, requires facilities and planning, and raises ethical concerns. Therefore, the use of anthropomorphic phantoms could be an excellent substitute. The aim of the study [...] Read more.
Background: Neurosurgical procedures are complex and require years of training and experience. Traditional training on human cadavers is expensive, requires facilities and planning, and raises ethical concerns. Therefore, the use of anthropomorphic phantoms could be an excellent substitute. The aim of the study was to design and develop a patient-specific 3D-skull and brain model with realistic CT-attenuation suitable for conventional and augmented reality (AR)-navigated neurosurgical simulations. Methods: The radiodensity of materials considered for the skull and brain phantoms were investigated using cone beam CT (CBCT) and compared to the radiodensities of the human skull and brain. The mechanical properties of the materials considered were tested in the laboratory and subsequently evaluated by clinically active neurosurgeons. Optimization of the phantom for the intended purposes was performed in a feedback cycle of tests and improvements. Results: The skull, including a complete representation of the nasal cavity and skull base, was 3D printed using polylactic acid with calcium carbonate. The brain was cast using a mixture of water and coolant, with 4 wt% polyvinyl alcohol and 0.1 wt% barium sulfate, in a mold obtained from segmentation of CBCT and T1 weighted MR images from a cadaver. The experiments revealed that the radiodensities of the skull and brain phantoms were 547 and 38 Hounsfield units (HU), as compared to real skull bone and brain tissues with values of around 1300 and 30 HU, respectively. As for the mechanical properties testing, the brain phantom exhibited a similar elasticity to real brain tissue. The phantom was subsequently evaluated by neurosurgeons in simulations of endonasal skull-base surgery, brain biopsies, and external ventricular drain (EVD) placement and found to fulfill the requirements of a surgical phantom. Conclusions: A realistic and CT-compatible anthropomorphic head phantom was designed and successfully used for simulated augmented reality-led neurosurgical procedures. The anatomic details of the skull base and brain were realistically reproduced. This phantom can easily be manufactured and used for surgical training at a low cost. Full article
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20 pages, 3233 KiB  
Article
Machine Learning for Shape Memory Graphene Nanoribbons and Applications in Biomedical Engineering
by Carlos León and Roderick Melnik
Bioengineering 2022, 9(3), 90; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9030090 - 23 Feb 2022
Cited by 6 | Viewed by 3126
Abstract
Shape memory materials have been playing an important role in a wide range of bioengineering applications. At the same time, recent developments of graphene-based nanostructures, such as nanoribbons, have demonstrated that, due to the unique properties of graphene, they can manifest superior electronic, [...] Read more.
Shape memory materials have been playing an important role in a wide range of bioengineering applications. At the same time, recent developments of graphene-based nanostructures, such as nanoribbons, have demonstrated that, due to the unique properties of graphene, they can manifest superior electronic, thermal, mechanical, and optical characteristics ideally suited for their potential usage for the next generation of diagnostic devices, drug delivery systems, and other biomedical applications. One of the most intriguing parts of these new developments lies in the fact that certain types of such graphene nanoribbons can exhibit shape memory effects. In this paper, we apply machine learning tools to build an interatomic potential from DFT calculations for highly ordered graphene oxide nanoribbons, a material that had demonstrated shape memory effects with a recovery strain up to 14.5% for 2D layers. The graphene oxide layer can shrink to a metastable phase with lower constant lattice through the application of an electric field, and returns to the initial phase through an external mechanical force. The deformation leads to an electronic rearrangement and induces magnetization around the oxygen atoms. DFT calculations show no magnetization for sufficiently narrow nanoribbons, while the machine learning model can predict the suppression of the metastable phase for the same narrower nanoribbons. We can improve the prediction accuracy by analyzing only the evolution of the metastable phase, where no magnetization is found according to DFT calculations. The model developed here allows also us to study the evolution of the phases for wider nanoribbons, that would be computationally inaccessible through a pure DFT approach. Moreover, we extend our analysis to realistic systems that include vacancies and boron or nitrogen impurities at the oxygen atomic positions. Finally, we provide a brief overview of the current and potential applications of the materials exhibiting shape memory effects in bioengineering and biomedical fields, focusing on data-driven approaches with machine learning interatomic potentials. Full article
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15 pages, 5809 KiB  
Article
Distinct Methodologies to Produce Capped Mesoporous Silica with Hydroxyapatite and the Influence in Intracellular Signaling as Cytotoxicity on Human Umbilical Vein Endothelial Cells
by Aline Oliveira da Silva de Barros, Luciana Magalhães Rebêlo Alencar, Frank Alexis and Ralph Santos-Oliveira
Bioengineering 2021, 8(9), 125; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering8090125 - 12 Sep 2021
Cited by 3 | Viewed by 2417
Abstract
Mesoporous silica has unique properties such as controllable mesoporous structure and size, good biocompatibility, high specific surface area, and large pore volume. For that reason, this material has been broadly functionalized for biomedical applications, such as optical imaging, magnetic resonance imaging (MRI), positron [...] Read more.
Mesoporous silica has unique properties such as controllable mesoporous structure and size, good biocompatibility, high specific surface area, and large pore volume. For that reason, this material has been broadly functionalized for biomedical applications, such as optical imaging, magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), ultrasound imaging, and widely employed as drug delivery systems. In this study, we synthesized fiber-type mesoporous silica capped with hydroxyapatite (ordered SiO2–CaO–P2O5 mesoporous silica). Its biological activity was evaluated through a cellular and molecular approach using HUVEC cell culture. Two distinct methodologies have produced the ordered SiO2–CaO–P2O5 mesoporous silica: (i) two-step Ca-doped silica matrix followed by hydroxyapatite crystallization inside the Ca-doped silica matrix and (ii) one-step Ca-doped silica matrix formed with the hydroxyapatite crystallization. Further analysis included: elemental analysis, transmission, scanning electron microscopy images, Small and Wide-Angle X-ray Diffraction analysis, Fourier Transform Infrared, and in vitro assays with HUVEC (cytotoxicity and immunoblotting). The hydroxyapatite capping methodology significantly affected the original mesoporous material structure. Furthermore, no cellular or molecular effect has been observed. The promising results presented here suggest that the one-step method to obtain hydroxyapatite capped mesoporous silica was effective, also demonstrating that this material has potential in biomedical applications. Full article
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26 pages, 755 KiB  
Article
Thermo-Viscoelastic Response of Protein-Based Hydrogels
by Aleksey D. Drozdov and Jesper deClaville Christiansen
Bioengineering 2021, 8(6), 73; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering8060073 - 31 May 2021
Cited by 1 | Viewed by 3031
Abstract
Because of the bioactivity and biocompatibility of protein-based gels and the reversible nature of bonds between associating coiled coils, these materials demonstrate a wide spectrum of potential applications in targeted drug delivery, tissue engineering, and regenerative medicine. The kinetics of rearrangement (association and [...] Read more.
Because of the bioactivity and biocompatibility of protein-based gels and the reversible nature of bonds between associating coiled coils, these materials demonstrate a wide spectrum of potential applications in targeted drug delivery, tissue engineering, and regenerative medicine. The kinetics of rearrangement (association and dissociation) of the physical bonds between chains has been traditionally studied in shear relaxation tests and small-amplitude oscillatory tests. A characteristic feature of recombinant protein gels is that chains in the polymer network are connected by temporary bonds between the coiled coil complexes and permanent cross-links between functional groups of amino acids. A simple model is developed for the linear viscoelastic behavior of protein-based gels. Its advantage is that, on the one hand, the model only involves five material parameters with transparent physical meaning and, on the other, it correctly reproduces experimental data in shear relaxation and oscillatory tests. The model is applied to study the effects of temperature, the concentration of proteins, and their structure on the viscoelastic response of hydrogels. Full article
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12 pages, 2248 KiB  
Article
Surface Engineered Iron Oxide Nanoparticles Generated by Inert Gas Condensation for Biomedical Applications
by Aver Hemben, Iva Chianella and Glenn John Thomas Leighton
Bioengineering 2021, 8(3), 38; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering8030038 - 15 Mar 2021
Cited by 11 | Viewed by 3672
Abstract
Despite the lifesaving medical discoveries of the last century, there is still an urgent need to improve the curative rate and reduce mortality in many fatal diseases such as cancer. One of the main requirements is to find new ways to deliver therapeutics/drugs [...] Read more.
Despite the lifesaving medical discoveries of the last century, there is still an urgent need to improve the curative rate and reduce mortality in many fatal diseases such as cancer. One of the main requirements is to find new ways to deliver therapeutics/drugs more efficiently and only to affected tissues/organs. An exciting new technology is nanomaterials which are being widely investigated as potential nanocarriers to achieve localized drug delivery that would improve therapy and reduce adverse drug side effects. Among all the nanocarriers, iron oxide nanoparticles (IONPs) are one of the most promising as, thanks to their paramagnetic/superparamagnetic properties, they can be easily modified with chemical and biological functions and can be visualized inside the body by magnetic resonance imaging (MRI), while delivering the targeted therapy. Therefore, iron oxide nanoparticles were produced here with a novel method and their properties for potential applications in both diagnostics and therapeutics were investigated. The novel method involves production of free standing IONPs by inert gas condensation via the Mantis NanoGen Trio physical vapor deposition system. The IONPs were first sputtered and deposited on plasma cleaned, polyethylene glycol (PEG) coated silicon wafers. Surface modification of the cleaned wafer with PEG enabled deposition of free-standing IONPs, as once produced, the soft-landed IONPs were suspended by dissolution of the PEG layer in water. Transmission electron microscopic (TEM) characterization revealed free standing, iron oxide nanoparticles with size < 20 nm within a polymer matrix. The nanoparticles were analyzed also by Atomic Force Microscope (AFM), Dynamic Light Scattering (DLS) and NanoSight Nanoparticle Tacking Analysis (NTA). Therefore, our work confirms that inert gas condensation by the Mantis NanoGen Trio physical vapor deposition sputtering at room temperature can be successfully used as a scalable, reproducible process to prepare free-standing IONPs. The PEG- IONPs produced in this work do not require further purification and thanks to their tunable narrow size distribution have potential to be a powerful tool for biomedical applications. Full article
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13 pages, 2570 KiB  
Article
Adipose-Derived Stromal Cells Seeded on Integra® Dermal Regeneration Template Improve Post-Burn Wound Reconstruction
by Marcin Piejko, Karolina Radziun, Sylwia Bobis-Wozowicz, Agnieszka Waligórska, Eliza Zimoląg, Michał Nessler, Anna Chrapusta, Zbigniew Madeja and Justyna Drukała
Bioengineering 2020, 7(3), 67; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7030067 - 02 Jul 2020
Cited by 11 | Viewed by 4096
Abstract
Fibrosis of burn-related wounds remains an unresolved clinical issue that leads to patient disability. The aim of this study was to assess the efficacy of the transplantation of adipose-derived stromal cells seeded onto a collagen-based matrix in the reconstruction of burn-related scars. Here, [...] Read more.
Fibrosis of burn-related wounds remains an unresolved clinical issue that leads to patient disability. The aim of this study was to assess the efficacy of the transplantation of adipose-derived stromal cells seeded onto a collagen-based matrix in the reconstruction of burn-related scars. Here, we characterized an in vitro interaction between adipose-derived stromal cells and a collagen-based matrix, Integra®DRT. Our results show that transcription of pro-angiogenic, remodeling, and immunomodulatory factors was more significant in adipose-derived stromal cells than in fibroblasts. Transcription of metalloproteinases 2 and 9 is positively correlated with the collagenolytic activity of the adipose-derived stromal cells seeded onto Integra®DRT. The increase in the enzymatic activity corresponds to the decrease in the elasticity of the whole construct. Finally, we validated the treatment of a post-excision wound using adipose-derived stromal cells and an Integra®DRT construct in a 25-year-old woman suffering from burn-related scars. Scarless healing was observed in the area treated by adipose-derived stromal cells and the Integra®DRT construct but not in the reference area where Integra®DRT was applied without cells. This clinical observation may be explained by in vitro findings: Enhanced transcription of the vascular endothelial growth factor as well as remodeling of the collagen-based matrix decreased mechanical stress. Our experimental treatment demonstrated that the adipose-derived stromal cells seeded onto Integra®DRT exhibit valuable properties that may improve post-excision wound healing and facilitate skin regeneration without scars. Full article
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Review

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35 pages, 9651 KiB  
Review
A Review on Damage and Rupture Modelling for Soft Tissues
by Sai Naga Sri Harsha Chittajallu, Ashutosh Richhariya, Kwong Ming Tse and Viswanath Chinthapenta
Bioengineering 2022, 9(1), 26; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9010026 - 10 Jan 2022
Cited by 12 | Viewed by 3675
Abstract
Computational modelling of damage and rupture of non-connective and connective soft tissues due to pathological and supra-physiological mechanisms is vital in the fundamental understanding of failures. Recent advancements in soft tissue damage models play an essential role in developing artificial tissues, medical devices/implants, [...] Read more.
Computational modelling of damage and rupture of non-connective and connective soft tissues due to pathological and supra-physiological mechanisms is vital in the fundamental understanding of failures. Recent advancements in soft tissue damage models play an essential role in developing artificial tissues, medical devices/implants, and surgical intervention practices. The current article reviews the recently developed damage models and rupture models that considered the microstructure of the tissues. Earlier review works presented damage and rupture separately, wherein this work reviews both damage and rupture in soft tissues. Wherein the present article provides a detailed review of various models on the damage evolution and tear in soft tissues focusing on key conceptual ideas, advantages, limitations, and challenges. Some key challenges of damage and rupture models are outlined in the article, which helps extend the present damage and rupture models to various soft tissues. Full article
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23 pages, 2908 KiB  
Review
Sol-Gel Derived Hydroxyapatite Coatings for Titanium Implants: A Review
by Alaa Jaafar, Christine Hecker, Pál Árki and Yvonne Joseph
Bioengineering 2020, 7(4), 127; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7040127 - 14 Oct 2020
Cited by 101 | Viewed by 8642
Abstract
With the growing demands for bone implant therapy, titanium (Ti) and its alloys are considered as appropriate choices for the load-bearing bone implant substitutes. However, the interaction of bare Ti-based implants with the tissues is critical to the success of the implants for [...] Read more.
With the growing demands for bone implant therapy, titanium (Ti) and its alloys are considered as appropriate choices for the load-bearing bone implant substitutes. However, the interaction of bare Ti-based implants with the tissues is critical to the success of the implants for long-term stability. Thus, surface modifications of Ti implants with biocompatible hydroxyapatite (HAp) coatings before implantation is important and gained interest. Sol-gel is a potential technique for deposition the biocompatible HAp and has many advantages over other methods. Therefore, this review strives to provide widespread overview on the recent development of sol-gel HAp deposition on Ti. This study shows that sol-gel technique was able to produce uniform and homogenous HAp coatings and identified the role of surface pretreatment of Ti substrate, optimizing the sol-gel parameters, substitution, and reinforcement of HAp on improving the coating properties. Critical factors that influence on the characteristics of the deposited sol-gel HAp films as corrosion resistance, adhesion to substrate, bioactivity, morphological, and structural properties are discussed. The review also highlights the critical issues, the most significant challenges, and the areas requiring further research. Full article
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35 pages, 4428 KiB  
Review
Repositioning Natural Antioxidants for Therapeutic Applications in Tissue Engineering
by Pasquale Marrazzo and Cian O’Leary
Bioengineering 2020, 7(3), 104; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7030104 - 02 Sep 2020
Cited by 36 | Viewed by 6716
Abstract
Although a large panel of natural antioxidants demonstrate a protective effect in preventing cellular oxidative stress, their low bioavailability limits therapeutic activity at the targeted injury site. The importance to deliver drug or cells into oxidative microenvironments can be realized with the development [...] Read more.
Although a large panel of natural antioxidants demonstrate a protective effect in preventing cellular oxidative stress, their low bioavailability limits therapeutic activity at the targeted injury site. The importance to deliver drug or cells into oxidative microenvironments can be realized with the development of biocompatible redox-modulating materials. The incorporation of antioxidant compounds within implanted biomaterials should be able to retain the antioxidant activity, while also allowing graft survival and tissue recovery. This review summarizes the recent literature reporting the combined role of natural antioxidants with biomaterials. Our review highlights how such functionalization is a promising strategy in tissue engineering to improve the engraftment and promote tissue healing or regeneration. Full article
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12 pages, 867 KiB  
Review
VLSI Structures for DNA Sequencing—A Survey
by Mohammad A. Islam, Palash K. Datta and Harley Myler
Bioengineering 2020, 7(2), 49; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering7020049 - 31 May 2020
Cited by 3 | Viewed by 5229
Abstract
DNA sequencing is a critical functionality in biomedical research, and technical advances that improve it have important implications for human health. Novel methods by which sequencing can be accomplished in more accurate, high-throughput, and faster ways are in development. Here, we review VLSI [...] Read more.
DNA sequencing is a critical functionality in biomedical research, and technical advances that improve it have important implications for human health. Novel methods by which sequencing can be accomplished in more accurate, high-throughput, and faster ways are in development. Here, we review VLSI biosensors for nucleotide detection and DNA sequencing. Implementation strategies are discussed and split into function-specific architectures that are presented for reported design examples from the literature. Lastly, we briefly introduce a new approach to sequencing using Gate All-Around (GAA) nanowire Metal Oxide Semiconductor Field Effect Transistors (MOSFETs) that has significant implications for the field. Full article
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