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Design and additive manufacture of microphysiological perfusion systems for pharmaceutical screening of tissue engineered skeletal muscleRimington, Rowan P. January 2018 (has links)
The methodologies utilised by pharmaceutical companies for the toxicity screening of developmental drugs are currently based on outdated two-dimensional (2D) plate-based assay systems. Although such methods provide high-throughput analysis, limitations surrounding the biomimicry of the culture environment reduces the accuracy of testing, making the process cost and time inefficient. To significantly enhance the current methods, a screening platform that is both flexible in its design and is amenable toward physiologically representative engineered tissue is required. Incorporating a flow environment within the system elicits a variety of advantages over standard static cultures, pertinently the ability to couple the flow path with automated analytical systems via the use of intuitive software. Musculoskeletal pathological conditions account for £4.76 billion of NHS spending as of 2011 (Department of Health), affecting one in four of the UK adult population. Skeletal muscle, a highly metabolic and regenerative tissue, is involved in a wide variety of functional, genetic, metabolic and degenerative pathological conditions such as muscular dystrophy, diabetes, osteoarthritis, motor neuron disease and pertinently muscular weakness associated with aging populations. Skeletal muscle tissue engineering is centred on the in vitro creation of in vivo-like tissue within laboratory environments and seeks to aid the development of future therapies, by reliably elucidating the molecular mechanisms that regulate such conditions. However, the translation of such models toward systems amenable to pharmaceutical companies has to date been limited. Microphysiological perfusion bioreactors for in vitro cell culture are a rapidly developing research niche, although state of the art systems are currently limited due to the biologically non-representative 2D culture environment, lack of adaptability toward different experimental requirements and confinement to offline analytical methods. Advancements in additive manufacture (AM), commonly known as three-dimensional (3D) printing has provided a method of production that enables researchers to hold complete design freedom and facilitate customisation of required parts. The low cost, rapid prototyping nature of AM further lends itself toward the development of such technology, with design iterations quickly and easily printed, tested and re-designed where appropriate. Issues do however, currently persist regarding the biological compatibility of printed polymers and functional material properties of parts created. As such, this thesis investigated the use of AM as a rapid and functional prototyping technique to design and develop microphysiological perfusion bioreactors. Here, biocompatibility of candidate polymers derived from commercially available 3D printing processes; fused deposition modelling (FDM), stereolithography (SL), selective laser sintering (LS) and PolyJet modelling (PJM) were elucidated. Following the biological evaluation of these polymers, their suitability, and the applicability of each process in function and manufacture of perfusion bioreactors were assessed alongside the research and development process of system designs. Specifically, attention was afforded to the homeostatic environment within bio-perfusion systems. Once finalised, the biological optimisation of designs; biocompatibility and rates of proliferation in response to the perfusion environment, was undertaken. Protocols were then established for the automated perfusion of skeletal muscle cells in both monolayer and tissue engineered 3D hydrogels. This research outlined significant contributions to the scientific literature in 3D printed polymer biocompatibility, in addition to creating bio-perfusion systems that are adaptable, analytical and facilitate the in situ phenotypic development of physiologically representative skeletal muscle tissue. Polymer biocompatibility elucidated in this work will help to facilitate the wide-ranging use of AM in biological settings. However, advancements in the chemical properties of liquid resins for advanced photo-curable processes remain necessitated for AM to be considered as a primary manufacturing technique in the biological sciences. Furthermore, although systems developed in this work have provided a base technology from which to develop and build upon, significant challenges remain in the integration of tissue engineered perfusion devices within pharmaceutical settings. Although it is plausible that the technology created in its current guise would facilitate the automated generation of skeletal muscle tissue, systems require further development to aid their usability and scale. Furthermore, work is also required to optimise the biological environment prior to mass manufacture. As such, to truly influence the pharmaceutical industry, which has invested so heavily in more traditional screening technology, a system that is all-encompassing in biology, technology and automated analytics is required.
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Improvement of 3D printing quality for fabricating soft scaffoldsWeibin, Lin 20 August 2014 (has links)
Tissue engineering (TE) integrates methods of cells, engineering and materials to improve or replace biological functions of native tissues or organs. 3D printing technologies have been used in TE to produce different kinds of tissues. Based on review of the exiting 3D printing technologies used in TE, special requirements of fabricating soft scaffolds are identified. Soft scaffolds provide a microenvironment with biocompatibility for living cells proliferation. This research focuses on 3D printer design and printing parameters investigation for fabrication of soft scaffolds. A 3D printer is proposed for producing artificial soft scaffolds, with components of a pneumatic dispenser, a temperature controller and a multi-nozzle changing system. Relations of 3D printing parameters are investigated to improve the printing quality of soft scaffolds. It provides guidance for printing customized bio-materials with improved efficiency and quality. In the research, printing parameters are identified and classified based on existing research solutions. A deposition model is established to analyze the parameters relations. Quantitative criteria of parameters are proposed to evaluate the printing quality. A series of experiments including factors experiments and comparison tests are conducted to find effects of parameters and their interactions. A case study is conducted to verify the analytic solution of proposed models. This research confirms that the hydrogel concentration and nozzle diameters have significant effects on the filament diameter. Factor interactions are mainly embodied in between the concentration of hydrogel solutions and dispensing pressures. Besides filament diameters, the nozzle height and space also affect the printing accuracy significantly. An appropriate nozzle height is considered to be 1.4 times than the nozzle diameter, and a reasonable nozzle space is suggested from 2.0 to 2.5 times of the nozzle diameter.
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GAME-CENTERED GAMEPADS: FABRICATING AND 3D PRINTINGRajguru, Chinmay 01 December 2017 (has links)
Fabricating and 3D printing gamepads is challenging not only in terms of appearance of them but also in terms of their physical validity and user experience that they might provide. This thesis addresses the issue of providing users the ability to hold in their hand a fabricated gamepad, which is an object similar to that the virtual character keeps in his/her hand inside the virtual world. Thus, this thesis presents a basic approach for converting 3D objects found in a variety of online datasets to functional gamepads by retargeting the structure of the gamepad’s buttons to the 3D model. The fabricated gamepads can then be used by gamers to enjoy their favorite game. The authors assumed that gamepads that have a relationship with the game enhance the game experience of users. This assumption is mainly based on a variety of previous work that investigates the use of “natural” interfaces. Therefore, in addition to the proposed approach, a two-part user study was also conducted to firstly understand whether the fabricated gamepads can be considered as valid physical objects and also to understand the way that participants experienced a game. First, the results indicated that the fabricated gamepads can be considered as valid physical objects and secondly, that they enhance the gaming experience of the users.
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A Study on the Use of Kilohertz Acoustic Energy for Aluminum Shaping and Mass Transport in Ambient Condition Metal 3D PrintingJanuary 2016 (has links)
abstract: This research work demonstrates the process feasibility of Ultrasonic Filament Modeling process as a metal additive manufacturing process. Additive manufacturing (or 3d printing) is the method to manufacture 3d objects layer by layer. Current direct or indirect metal additive manufacturing processes either require a high power heat source like a laser or an electron beam, or require some kind of a post processing operation to produce net-shape fully-dense 3D components. The novel process of Ultrasonic Filament Modeling uses ultrasonic energy to achieve voxel deformation and inter-layer and intra-layer mass transport between voxels causing metallurgical bonding between the voxels. This enables the process to build net-shape 3D components at room temperature and ambient conditions. Two parallel mechanisms, ultrasonic softening and enhanced mass transport due to ultrasonic irradiation enable the voxel shaping and bonding respectively. This work investigates ultrasonic softening and the mass transport across voxels. Microstructural changes in aluminium during the voxel shaping have also been investigated. The temperature evolution during the process has been analyzed and presented in this work. / Dissertation/Thesis / Masters Thesis Engineering 2016
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Making Fabrication Real: Fabrication for Real Usage, with Real Objects, by Real PeopleChen, Xiang 01 December 2017 (has links)
The increasingly personal and ubiquitous capabilities of computing—everything from smartphones to virtual reality—are enabling us to build a brave new world in the digital realm. Despite these advances in the virtual world, our ability as end-users to transform the physical world still remains limited. The emergence of low-cost fabrication technology (most notably 3D printing) has brought us a dawn of making, promising to empower everyday users with the ability to fabricate physical objects of their own design. However, the technology itself is oblivious of the physical world—things are, in most cases, assumed to be printed from scratch in isolation from the real world objects they will be attached to and work with. To bridge this ‘gulf of fabrication’, my thesis research focuses on developing fabrication techniques with design tool integration to enable users to expressively create designs that can be attached to and function with existing real-world objects. Specifically, my work explores techniques that leverage the 3D printing process to create attachments directly over, onto and around existing objects; a design tool further enables people to specify and generate adaptations that can be attached to and mechanically transform existing objects in user-customized ways; a user-driven approach allows people to express and iterate structures that are optimized to support existing objects; finally, a library of ‘embeddables’ demonstrate that existing objects can also augment 3D printed designs by embedding a large variety of material to realize different properties and functionalities. Overall my thesis aspires to make fabrication real—enabling people to express, iterate and fabricate their designs that closely work with real-world objects to augment one another.
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Macromolecular Engineering and Additive Manufacturing of Poly(styrene-b-isobutylene-b-styrene) (SIBS)Shen, Naifu 04 August 2021 (has links)
No description available.
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High-precision fabrication enables on-chip modeling with organ-level structural and mechanical complexityMichas, Christos 25 September 2021 (has links)
Organ-on-chip models are a rapidly evolving and promising tool for studying human physiology and disease and developing therapeutics. However, due to the lack of fabrication processes of pertinent precision to deliver well-defined architectural and mechanical elements, organ-on-chip models have been limited in recapitulating structural and biomechanical features of many tissues, which has impeded the modeling power and clinical relevance of these tools. The elusive in vitro replication of the pumping function and mechanical loading of the human heart, an outstanding instance of a structurally and mechanically complex physiological system, exemplifies the need for stronger fabrication processes.
In this work, we investigated the potential of two-photon direct laser writing (TPDLW), an emerging high-precision fabrication technique, in enabling the generation of structurally and biomechanically complex organ-on-chip models. We first identify the functional principles, advantages and limitations of TPDLW, and review existing applications of TPDLW for in vitro studies. Inspired by the fabrication versatility of TPDLW, we then engineer a microfluidic cardiac pump powered by human stem-cell-derived cardiomyocytes (hiPSC-CM), aiming to replicate the ventricular pumping function on a chip by constructing miniaturized analogues of the functional elements of the human heart. We specifically fabricate a microscale metamaterial scaffold with fine-tuned mechanical properties to support the formation and cyclic contraction of an unprecedentedly miniaturized induced pluripotent stem cell derived ventricular chamber. Furthermore, we fabricate microfluidic valves with extreme sensitivity to rectify the flow generated by the ventricular chamber. The integrated microfluidic system recapitulates ventricular fluidic function and exhibits for the first time in vitro all phases of the ventricular hemodynamic loading pattern. Finally, we demonstrate a technique of increasing the fabrication output of TPDLW that could enable its broader adoption. Together, our results highlight the potential of high-precision fabrication in expanding the accessible spectrum of organ-on-a-chip models towards structurally and biomechanically sophisticated tissue architectures.
This dissertation is accompanied by a set of supplementary videos depicting the results of our experimental efforts. Movie 1 shows a cardiac tissue beating on an inverted hexagon scaffold. Movie 2 shows a compressive test on helical scaffold that is later embedded in a cardiac tissue. Movie 3 show a beating cardiac chamber on helical scaffold that can generate measurable flow. Movie 4 shows a functional suspension valve that is later embedded in the device with the cardiac chamber. Movie 5 shows the function of a suspension valve that rectifies oscillating flow. Movie 6 shows that the same suspension valve can rectify flow of increasing frequency. Movie 7 shows that the combined chamber and valves exhibit directional flow. Finally, movie 8 shows that the addition of afterload in the combined system leads to the emergence of isovolumetric phases. / 2023-09-24T00:00:00Z
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Design, fabrication, and reduction to practice of milliscale membrane-free organ chip systemsJanuary 2021 (has links)
archives@tulane.edu / The goal of this research was to establish a novel digital manufacturing-based workflow for the fabrication of membrane free organ chip (MFOC) systems. This workflow is based on the implementation of top-down design, starting with CAD design of molds for MFOC components and can be conducted on a benchtop removing the need for cleanroom use. In conducting this research, a commercially available SLA printer was characterized and optimized for manufacturing molds suitable for MFOC fabrication. To achieve this, extensive research was required to determine printer resolution limits and work within the limitations of the resins available for printing. Specifically, the molds need to be flat and smooth in order to produce perfectly horizontal and transparent PDMS devices. Post-processing workflows were engineered to satisfy these MFOC design constraints. After establishing a reliable and reproducible workflow for MFOC fabrication, the focus of the research was reduction to practice, i.e. achieving a design that enables loading MFOC with patterned aqueous solutions with 100% success and a high degree of forgiveness. Key MFOC dimensions were systematically varied in a manner only possible with the rapid prototyping capability of DM in a series of experiments with a standardized injection test and success rate of loading as the primary output. With a robust MFOC design in place, more complex designs for tissue patterning applications were created, and advanced configurations for engineering patterned vascularized stromal tissues were tested and validated. Seqeuntial and simultaneous loading scenerios were imvestigated to better understand cell migration impedence in multi-gel lane devices. / 1 / William Bralower
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A co-culture microplate platform to quantify microbial interactions and growth dynamicsJo, Charles 30 August 2019 (has links)
This thesis reports the development of BioMe, a co-culture microplate platform that enables high-throughput, real-time quantitative growth dynamics measurements of interacting microbial batch cultures. The primary BioMe components can be 3D-printed, allowing ease of fabrication and DIY accessibility in the microbiome community. A pairwise 3D-printed iteration of the BioMe device was used in diffusion and co-culture experiments. Genetically engineered Escherichia Coli lysine and isoleucine auxotroph strains were used to characterize the diffusion of amino acids across the porous membranes. Results demonstrated a nonlinear relationship between growth rate and pore size and also distinct diffusion behavior for lysine and isoleucine. Pairwise syntrophic co-culture experiments demonstrated synergistic but repressed interaction between these two paired auxotrophs. Investigation of the effect of varying initial amino acid conditions on growth dynamics demonstrated that small changes in initial media condition can consistently affect patterns of yield and growth rate of constituent microbial species. / 2020-08-30T00:00:00Z
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Comparison of the accuracy between 3D printed and milled dental models by a digital inspection softwareAlvi, Shan 27 October 2017 (has links)
STATEMENT OF PROBLEM: The production of full arch dental models through Rapid Additive Prototyping (3D Printing) have been questioned for their accuracy in the past decade.
PURPOSE: To compare the accuracy of 3D printed and milled dental models, using a digital metrology software.
MATERIALS AND METHOD: A mandibular arch typodont was duplicated to produce a conventional Type IV dental stone model. This Model was scanned to create a digital model and an STL file was created which would be sent to Milling and 3D printing machines.15 models were printed using 3 different 3D printing companies and 10 models Milled with a CNC (Computerized Numeric Controlled) milling machine. Each model was scanned and a digital model was created. These scanned models were then super imposed to the scan of the master model through an inspection software (Geomagic Control X, 3D Systems) for accuracy of production.
RESULTS: The mean difference in measurement in Absolute Gap, by either of the two methods of prototyping adopted, (0.075 mm for 3D Printed and 0.084 mm for milled) are well below the clinically acceptable values mentioned in previous literature.
The means in absolute tooth distance discrepancy for both prototyping methods (0.0361 mm for 3DPand 0.0353 mm for Milled) were not statistically significant.
CONCLUSION: 3D printed dental models were more accurate statistically than milled dental models. In general, the mean accuracy for both methods of rapid prototyping is within clinical tolerance and both are clinically acceptable.
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