• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 926
  • 574
  • 148
  • 126
  • 119
  • 59
  • 31
  • 28
  • 13
  • 12
  • 10
  • 9
  • 8
  • 8
  • 8
  • Tagged with
  • 2413
  • 479
  • 451
  • 394
  • 251
  • 203
  • 190
  • 169
  • 164
  • 161
  • 155
  • 151
  • 122
  • 121
  • 116
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
511

Fracionamento isot?pico do 15N na fixa??o biol?gica de nitrog?nio na soja em fun??o da intensidade de luz e estirpe de Bradyrhizobium spp. Inoculada / Isotopic fractionation of 15N in nitrogen fixation in soybean due to light intensity and Bradyrhizobium spp. strain inoculated

Ara?jo, Karla Emanuelle Campos 29 July 2014 (has links)
Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2017-08-28T14:10:07Z No. of bitstreams: 1 2014 - Karla Emanuelle Campos Araujo.pdf: 681239 bytes, checksum: 370286856e74db8636cdc28b6d35e0b6 (MD5) / Made available in DSpace on 2017-08-28T14:10:07Z (GMT). No. of bitstreams: 1 2014 - Karla Emanuelle Campos Araujo.pdf: 681239 bytes, checksum: 370286856e74db8636cdc28b6d35e0b6 (MD5) Previous issue date: 2014-07-29 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / ARAUJO, Karla Emanuelle Campos. Isotopic fractionation of 15N in nitrogen fixation in soybean due to light intensity and Bradyrhizobium spp. strain inoculated. 2014. 40f. Dissertation (Master in Plant Science). Institute of Agronomy, Department of Plant Science, Federal Rural University of Rio de Janeiro, Serop?dica, RJ, 2014. This work aimed to study the isotopic fractionation of N from BNF in stems function and light intensity in soybean plant symbiosis with Bradyrhizobium. The 'B' value was evaluated for ten Bradyrhizobium strains, as well as their interaction with the soybean plant (Glycine max L.). The experiment was conducted at Embrapa greenhouse Agrobiologia, Serop?dica, RJ. The soybean plants inoculated with the different strains of Bradyrhizobium and a control not inoculated, were grown under conditions similar to Leonard vessels using substrate of sand and vermiculite in a 2: 1 (v / v). In the second experiment to assess the value 'B' of the resulting symbiosis BNF among cultivars (cv) of soybean BRS 133, BRS 184, MONSOY9144 nine Bradyrhizobium. Soybean plants in all the treatments, were grown under the same conditions, the soybean cultivation was performed in vessels Leonard with sand and perlite substrate in the proportion 1: 1 (v / v). In both experiments after 47 days of planting the plants were harvested and calculated the value 'B'. In the third experiment evaluated the effect of different strains of Bradyrhizobium and the reduction in the intensity of light on natural abundance of 15N N2 fixed by the strains in symbiosis with soybean cv BRS 133. An experiment was conducted in the experimental field of Embrapa Agrobiology. The soybean plants inoculated with 11 Bradyrhizobium and treatment uninoculated were grown under similar conditions in plastic pots with sand substrate and pearlite in the proportion 1: 1 (v / v) .After 75 days after planting the plants were collected and calculated the value 'B'.No experiment 1, the values of ?Bpa? ranged between -2 and -4 ?, according to the strain used. In experiment 2, the values of ?Bpa? showed no difference between the soybean cultivars inoculated with Bradyrhizobium as the isotopic abundance of 15N in plants grown entirely dependent on FBN. There was a tendency for the abundance of 15N values in ?Bpa? treatment of plants inoculated with strains of B. elkanii to be less negative than in the case of plants inoculated with B. japonicum. In experiment 3 the values of ?B?PA showed natural 15N abundance values significantly more negative than the shaded plants. There was a tendency for the abundance of 15N in the shoot (and values of ?Bpa?) treatment of the plants inoculated with B. japonicum strains to be less negative than in the case of plants inoculated with B. elkanii. For the determination of the 'B' value, the plants should be in the same stage of maturity that being used to sample the plants in the field, to assess the value 'B' in low light intensity conditions (green house) can lead to the result of a 'B' value less negative than that given in full sun and so probably less appropriate uses it to calculate the contribution of BNF in legume under field conditions. / ARAUJO, Karla Emanuelle Campos. Fracionamento isot?pico do 15N na fixa??o biol?gica de nitrog?nio na soja em fun??o da intensidade de luz e estirpe de Bradyrhizobium spp. inoculada. 2014. 40f. Disserta??o (Mestrado em Fitotecnia). Instituto de Agronomia, Departamento de Fitotecnia, Universidade Federal Rural do Rio de Janeiro, Serop?dica, RJ, 2014. Este trabalho teve como objetivo estudar o fracionamento isot?pico do N proveniente da FBN, em fun??o de estipes e intensidade de luz na simbiose da planta de soja com Bradyrhizobium. O valor ?B? foi avaliado para dez estirpes de Bradyrhizobium, assim como sua intera??o com a planta de soja (Glycine max, L.). Foi conduzido o experimento na casa de vegeta??o da Embrapa Agrobiologia, Serop?dica, RJ. As plantas de soja inoculadas com as diferentes estirpes de Bradyrhizobium e um controle, n?o inoculado, foram crescidas em condi??es semelhantes em vasos Leonard, utilizando substrato de areia e vermiculita na propor??o 2:1 (v/v). No segundo experimento para avaliar o valor ?B? da FBN resultante da simbiose entre as cultivares (cv) de soja BRS 133, BRS 184, MONSOY9144 e nove estirpes de Bradyrhizobium. As plantas de soja para todos os tratamentos, foram crescidas em condi??es iguais, o cultivo da soja foi realizado em vasos Leonard, utilizando substrato de areia e perlita na propor??o 1:1 (v/v). Nos dois experimentos ap?s 47 dias do plantio as plantas foram colhidas e calculou o valor ?B?. No terceiro experimento avaliou-se o efeito de diferentes estirpes de Bradyrhizobium e da redu??o na intensidade de luz sobre abund?ncia natural de 15N do N2 fixado pelas estirpes em simbiose com a cv. de soja BRS 133. Foi conduzido um experimento no campo experimental da Embrapa Agrobiologia. As plantas de soja inoculadas com 11 estirpes de Bradyrhizobium e um tratamento n?o inoculado, foram crescidas em condi??es semelhantes em vasos pl?sticos, utilizando substrato de areia e perlita na propor??o 1:1 (v/v). Ap?s 75 dias do plantio as plantas foram colhidas e calculou-se o valor ?B?. No experimento 1, os valores de ?Bpa? variaram entre -2 e -4 ?, de acordo com a estirpe usada. No experimento 2, os valores de ?Bpa? n?o apresentaram diferen?a entre as cultivares de soja inoculadas com os Bradyrhizobium quanto a abund?ncia isot?pica de 15N nas plantas crescida inteiramente dependente da FBN. Houve uma tend?ncia para a abund?ncia de 15N nos valores de ?Bpa? das plantas dos tratamentos inoculados com estirpes de B. elkanii a serem menos negativo do que no caso de plantas inoculadas com B. japonicum. No experimento 3 os valores de ?Bpa? apresentaram valores de abund?ncia natural de 15N significativamente mais negativos do que as plantas sombreadas. Houve uma tend?ncia para a abund?ncia de 15N na parte a?rea (e os valores de ?Bpa?) das plantas dos tratamentos inoculados com estirpes de B. japonicum a serem menos negativo do que no caso de plantas inoculadas com B. elkanii. Para ? determina??o do valor ?B?, as plantas devem estar no mesmo est?gio de maturidade que as que est?o sendo utilizadas para amostrar as plantas no campo, a avalia??o do valor ?B? em condi??es de intensidade de luz reduzida (casa de vegeta??o) pode levar ao resultado de um valor ?B? menos negativo do que aquele determinado em pleno sol e assim provavelmente menos apropriado utiliza-lo, para calcular a contribui??o da FBN em leguminosa em condi??es de campo.
512

Dépôt contrôlé de nanoparticules magnétiques par électrospray et nanodispending / Controlled deposition of magnetic nanoparticles by electrospray nanodispending

Agostini, Pierre 05 December 2014 (has links)
Les nanoparticules (NP) magnétiques ont potentiellement de nombreux débouchés technologiques notamment en oncologie, dans la confection d’aimants permanents ou pour le stockage informatique à très haute densité. Cependant, leurs propriétés magnétiques sont aujourd’hui mal connues car les techniques de caractérisation existantes ne sont pas assez performantes. Une technique prometteuse offrant la possibilité de mesurer précisément les propriétés magnétiques d’une NP unique est le résonateur mécanique à nanotube de carbone (RMNC). L’enjeu de ma thèse a été de développer une technique pour déposer une NP magnétique unique sur un RMNC. Nous avons menés en parallèle l’étude de deux techniques, le NAnoscale DIspensing System (NADIS®) et l’électrospray. Les différentes expériences menées m’ont permis de contrôler le dépôt de NP unique de polystyrène avec NADIS et de NP uniques de Fe et FeCo d’une dizaine de nanomètre avec l’électrospray sur une surface vierge. Ceci m’a permis de valider la faisabilité de déposer une NP unique sur un RMNC. / Magnetic nanoparticles have potentially many technology opportunities including oncology, manufacture of permanent magnets or computer storage at very high density. However, their magnetics properties are not well known today because the existing characterization techniques are not enough efficient. A promising technique offering the ability to accurately measure the magnetic properties of a single NP is the carbon nanotube mechanical resonator (CNMR). The challenge of my PhD has been to develop a technique for depositing a single magnetic NP on CNMR. We study two techniques in parallel, Nanoscale Dispensing System (NADIS®) and electrospray. The different experiences led have allowed me to control the deposition of a single polystyrene NP with NADIS and unique Fe and FeCo NP of ten nanometers with electrospray onto a free surface. This allowed me to validate the feasibility of depositing a single NP on a CNMR.
513

Morphing Structures : An exploration of the fusion between marbled coating and triaxial weave

Benea, Claudia-Roxana January 2018 (has links)
The purpose of this study is to investigate the effects of a marbled coating applied on a triaxial woven structure. Although both of these techniques are traditionally used for many years, they are nowadays utilized in innovative ways, the marbling being applied on a large variety of surfaces such as wooden floors or ceramics and the triaxial weave being used as a hi-tech material for sports or in the automotive industry and having applications in diverse fields, from art to architecture. Their fusion, however, is a topic that has yet to be thoroughly explored, which makes for the motive of this thesis work, as an opening has been observed for the exploration of the expressive power of their combination. The experimental approach that has been taken towards this exploration will determine how the marbling effect may contribute to the visual expression of the structure. Multiple cycles of experiments have been conducted in an attempt to understand the behaviour of the chosen materials and their combination, the effect that various colour combinations have and the best possible pairings between the elements. The organic marbling combined with the geometric triaxial weave proved to generate the most powerful visual expression and the clearest result out of all the experiments. Thus five experimental textiles were developed in order to illustrate different aspects of this complex relationship, where the marbling would affect the visual expression of the structure by either enhancing or concealing the structural aspect and the contrast between the graphic element and the organic one would be a constant presence throughout the work. This work pushes the boundaries of conventional textile design and through the application of a textile thinking to unconventional materials a different type of expression is born. By mixing a limited amount of variables in multiple ways, a large range of visual effects may be achieved.
514

A clinical practice model of music therapy to address psychosocial functioning for persons with dementia: model development and randomized clinical crossover trial

Reschke-Hernández, Alaine Elizabeth 01 May 2019 (has links)
Background: By 2050, it is estimated that 14 million older Americans will live with Alzheimer’s disease (AD), a progressive form of dementia with unknown cause or cure. Persons with AD and related dementias (ADRD) become increasingly dependent on others as they experience cognitive decline, which concomitantly undermines individuals’ functional skills, social initiative, and quality of life. The Alzheimer’s Association advocates for interventions that address cognition, mood, behavior, social engagement, and by extension, quality of life – goals music therapists often address. Although a small but growing body of literature suggests that clinical music therapy may be effective, the evidentiary support for the use and appropriate application of music as a form of treatment with this population is currently limited. Objectives: This thesis consisted of the development of a Clinical Practice Model of music therapy for persons with ADRD. It also examined the effectiveness of a specific, protocol-based music therapy intervention, grounded in this model, relative to a verbal discussion activity. Methods: The Clinical Practice Model is theoretically grounded in the biopsychosocial model of healthcare (Engel, 1980) and Kitwood’s (1997) personhood framework, and I developed it through extensive literature review and expert input. It includes an organizational schema for applying intervention strategies, per six themes: cognition, attention, familiarity, audibility, structure, and autonomy. The initial model predicts that an intervention built upon this schema will influence social-affective responses, quality of life, and in turn, psychosocial symptoms of ADRD. I tested a singing-based music therapy intervention, grounded in this model, through a randomized clinical crossover trial. I compared participants’ responses to music therapy to a non-music verbal discussion activity, and both conditions followed a protocol. Dependent variables included: (1) affective responses (self-reported feelings, observed emotions, and observed mood), (2) social engagement, and (3) observed quality of life. Thirty-two individuals with ADRD (n = 6 men, n = 26 women) ages 65-97 years old (μ̂ = 84.13) participated in this study. I randomly assigned treatment order; each treatment occurred in small-group format, three times per week in the afternoon (25 minutes each session), for two consecutive weeks. A two-week “wash-out” period occurred between conditions. Credentialed music therapists led both study conditions. This study followed recommendations from the National Institutes of Health Behavior Change Consortium (Bellg et al., 2004) to enhance quality assurance in protocol administration and data collection. Results and Significance: I used a linear mixed model approach to analysis. Music therapy exacted a significant, positive effect on self-reported feelings, observed emotions, and constructive engagement, particularly for individuals with moderate dementia. Results also suggested that men’s feelings improved in response to music therapy only, whereas women responded positively to both conditions. Weekly observations failed to indicate a significant change in mood or quality of life across the eight-week study. Based on these findings, I revised the Clinical Practice Model to include wellbeing (an outcome more concordant with psychosocial change in response to music intervention) rather than global quality of life (affected by numerous aspects of the care milieu). In addition to the Clinical Practice Model to the music therapy profession, contributions of this thesis include a rigorous clinical study and practical implications for music therapy practice, including the importance of considering patient characteristics and careful selection and implementation of music in a music therapy intervention.
515

Effects of Mammalian Target of Rapamycin Inhibition on Circuitry Changes in the Dentate Gyrus of Mice after Focal Brain Injury

Butler, Corwin R. 01 January 2016 (has links)
Post-traumatic epilepsy is a common outcome of severe traumatic brain injury (TBI). The development of spontaneous seizures after traumatic brain injury generally follows a latent period of little to no symptoms. The series of events occurring in this latent period are not well understood. Additionally, there is no current treatment to prevent the development of epilepsy after TBI (i.e. antiepileptogenics). One cell signaling pathway activated in models of TBI and in models of epilepsy is the mammalian target of rapamycin (mTOR). mTOR activity is sustained for weeks after the initial insult in models of TBI, and the inhibition of mTOR using rapamycin has shown promising pre-clinical outcomes in rodent models. This makes rapamycin an ideal therapeutic to test various outcomes associated with epileptogenesis after TBI. The results from this study suggest that rapamycin treatment after controlled cortical impact reduces aberrant axonal sprouting of ipsilateral dentate granule cells, prevents increased neurogenesis in the subgranular zone, and differentially alters phasic and tonic inhibition in dentate granule cells. However, rapamycin treatment did not prevent all forms of axon sprouting in the dentate gyrus or cell loss in selected regions of the hippocampus. Collectively these results support a role of mTOR activity in both excitatory and inhibitory plasticity in the mouse dentate gyrus after TBI.
516

Facteurs de mobilisation des stratégies de compensation mnésique et de leurs efficacités dans le vieillissement / Factors of the mobilization of stratégies mnesique compensation and their effectiveness in aging

Mazzocco, Clémence 04 December 2015 (has links)
L’objectif général de ce travail de thèse était d’étudier l’impact des ressources antérieures des individus sur la compensation mnésique perçue (étude 1 et étude 2) ainsi que sur la compensation mnésique externe objective (étude 3). Afin d’opérationnaliser l’évaluation des stratégies de compensation mnésique perçues, l’étude 1 concernait la validation française et la normalisation du memory Compensation Questionnaire (F-MCQ) sur 749 personnes âgées de 18 ans à 92 ans. Afin d’adapter cet outil à différents contextes, nous avons procédé à la construction de sa version brève (BF-MCQ) ainsi qu’à sa validation sur 260 personnes âgées de 50 ans à 85 ans dans l’étude 2. Les résultats de ces deux travaux montrent une validité interne satisfaisante pour ces deux échelles, et la normalisation rend compte d’un effet de l’âge et du genre sur la perception des stratégies de compensation mnésique qu’un individu pense utiliser au quotidien. La validité externe des deux échelles met en évidence des liens entre le stress, l’efficacité mnésique et la personnalité avec les cinq stratégies de compensation mesurées par ces outils. Notre troisième étude a testé a) l’impact du trait de personnalité « Ouverture aux expériences » et des processus contrôlés dans l’utilisation d’une aide externe et dans son efficacité en situation de rappel prospectif chez 80 personnes âgées de 50 ans à 92 ans et b) le lien entre les observations comportementales des participants et leur propre perception de fonctionnement durant l’expérience. Les résultats montrent que seuls les processus contrôlés sont impliqués dans la mobilisation des stratégies externes et dans leur efficacité. Bien que les personnes âgées déclarent utiliser les aides externes quotidiennement et fréquemment dans le French Memory Compensation Questionnaire, nous n’avons pas retrouvé ce comportement de manière significative en situation. Au final, ces trois études nous permettent de considérer la compensation mnésique externe comme un processus qui dépend de l’auto-initiation des ressources cognitives, et de mettre en évidence l’impact de différents facteurs affectifs et psychosociaux dans la perception que les individus ont de leur mode compensatoire quotidien. / The general objective of this thesis was to study the impact of past resources of individuals on perceived memory compensation (Study 1 and Study 2) and on objective external memory compensation (Study 3). In order to operationalize the evaluation of perceived memory compensation strategies, Study 1 involved the French validation and normalization of the Memory Compensation Questionnaire (F-MCQ) of 749 participants aged from 18 to 92 years. In order to adapt this tool to different contexts, we created a shorter version (BF-MCQ) and conducted his validation on 260 participants aged from 50 years to 85 years in study 2. The results of these two works show a satisfactory internal validity for these two scales, and normalization reports an effect of age and gender on the perception of memory compensation strategies that an individual thinks that he use in everyday life. The external validity of these two scales showed the links between stress, self-memory efficiency and personality with the five compensation strategies measured by these tools. Our third study tested a) the impact of the personality trait "Openness" and of controlled processes on the use of external aid and on its effectiveness in prospective recall situation with 80 participants aged from 50 to 92 years and b) the link between behavioral observations of participants and their own perception of behavior during the experiment. The results show that only the controlled processes are involved in the mobilization of external strategies and in their effectiveness. Although seniors reported using external aids daily and frequently in the French Memory Compensation Questionnaire, we did not find this behavior to occur significantly in situation. In the end, these three studies allow us to consider the external memory compensation as a process that depends on self-initiation of cognitive resources, and to highlight the impact of various emotional and psycho affective factors in the perception that individuals have about their daily compensatory mode.
517

Formulation Development of a Polymer-Drug Matrix with a Controlled Release Profile for the Treatment of Glaucoma

Tsoi, Eric W. 01 December 2013 (has links)
Glaucoma is the leading cause of blindness in the United States accounting for 9-12% of all cases of blindness. Currently, the front line treatment for glaucoma are prostaglandins that may have to be taken up to several times a day. Even with proper treatment, roughly 11% of the patients using the treatment are non-compliant and lose their vision. In this project, ForSight Laboratories has developed a pharmaceutical drug delivering implant with the capability of sustaining long-term release of a prostaglandin as a new way to treat the condition. This project reports the product development of a polymer drug matrix with a controlled release in order to better treat glaucoma. Accompanying product development, a mathematical model was created in order to strengthen the understanding of the dosage profile and to predict long term dosages.
518

Development of a Bicycle Level of Service Methodology for Two-Way Stop-Controlled (TWSC) Intersections

Johnston, Nathan R 01 March 2014 (has links)
This thesis fills a missing piece in research on multimodal performance measures for traffic on streets and highways. The Highway Capacity Manual (HCM) published by the Transportation Research Board (TRB) provides Level of Service (LOS) methodologies which enable engineers and planners to evaluate the overall performance of roadways and highways based on the physical characteristics of facilities. This allows for the evaluation of those facilities and offers a means for recognizing issues and planning, designing, implementing, and ultimately assessing improvements. Originally, level of service was developed for automotive traffic only, but with recent developments as part of the complete streets movement, the performance of infrastructure for alternative transportation modes have also started being assessed in this fashion. There are methodologies in HCM 2010 for bicycle traffic at signalized intersections, all-way stop-controlled intersections, roadway and highway segments, but as of yet, no bicycle level of service methodology exists for two-way stop-controlled intersections. This work attempts to fill this gap. The methodology utilized for this report includes video collection of sample two-way stop-controlled intersections throughout California, collection of survey responses from viewers of video, and linear regression of collected survey responses with physical attributes of each sample intersection as the explanatory variables. Data was analyzed from both combined and individual street movements to determine the final equation set. The final methodology involves two separate procedures for major and minor streets at TWSC intersections. Final factors deemed significant in bicycle level of service analysis include sight distances, speed limits, presence of bus stops, presence and type of bicycle infrastructure, street widths and types of lanes present, pavement quality, and traffic flows.
519

Ask a Busy Person? A Reexamination of Cognitive Performance Under Load

Watson, Graham 01 January 2017 (has links)
A longstanding folk belief suggests that 'busy' people possess the ability to get more done than others. Busyness, defined as the demands of everyday life, has been shown to generate cognitive load, which has been called 'cognitive busyness.' Although most cognitive theory would deny the possibility that cognitive load may enhance performance, some recent research may support the possibility. Cowan's 1988 information-processing model was used to study how measures of everyday busyness correlated with performance on cognitive tasks. The research question addressed whether any combination of such measures, in combination with working memory, could predict performance on such tasks. 92 participants, paid workers with Amazon Mechanical Turk, engaged in an online process, starting with completion of a validated self-report instrument to measure busyness. They then participated in 2 activities, structured as games and designed to measure working memory and cognitive performance. Multiple regressions, linear and nonlinear, were used to identify significant predictors of performance. Results of the analyses did not reveal any evidence for significant relationships between the variables. Additionally, 'volitional busyness' did not appear to enhance, or even affect, performance on a planning task. Further research exploring the effect of these variables on a working memory-based task may be worthwhile, if only to confirm the present findings. This project might benefit linguists tracking semantic change, showing how a term may adopt an entirely different meaning and suggesting further refinement in identifying such shifts over the years; psychologists exploring cognitive load and its effects; and social psychologists interested in making corrections to popular perceptions of the value of tradition gender-associated tasks.
520

Controlled drug delivery systems and integration into 3D printing

Do, Anh-Vu Tran 01 August 2018 (has links)
Controlled drug delivery systems have been utilized to enhance the therapeutic effects of many current drugs by effectively delivering drugs in a time-dependent and repeatable manner. The ability to control the delivery of drugs, whether through sequential, instantaneous, sustained, delayed and/or enhanced release has the potential to provide effective dosing regimens with enhanced therapeutic effects for a plethora of diseases and injuries. For instance, such systems can enhance anti-tumoral responses or, alternatively, promoting tissue regeneration. The current need for organ and tissue replacement, repair and regeneration for patients is continually growing such that supply is not meeting the high demand primarily due to a paucity of donors as well as biocompatibility issues that lead to immune rejection of the transplant. To overcome this problem, scientists working in the field of tissue engineering and regenerative medicine have investigated the use of scaffolds as an alternative to transplantation. These scaffolds are designed to mimic the extracellular matrix (ECM) by providing structural support as well as promoting attachment, proliferation, and differentiation with the goal of yielding functional tissues or organs. Continued advancement and hybrid approaches using different material combinations and printing methodologies will further advance the progress of 3D printing technologies toward developing scaffolds, and other implantable drug delivery devices, capable of being utilized in the clinic. Such advancements will not only make inroads into improving structural integrity of implantable devices but will also provide platforms for controlled drug delivery from such devices. The primary focus of this thesis will be on controlled drug delivery as well as the integration of controlled drug delivery into 3D printed devices aimed at promoting tissue regeneration. We initially assessed the efficacy of a controlled drug delivery system for the treatment of cancer using on-demand, and sustained, release of an anticancer drug, doxorubicin (DOX), for the treatment of melanoma in a murine model. Using a melanoma model, we investigated the antitumor potential of combining ultrasound (US) with poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with DOX. An in vitro release assay demonstrated an ability of US to affect the release kinetics of DOX from DOX-loaded PLGA microspheres by inducing a 12% increase in rate of release where this treatment resulted in synergistic tumor cell (B16-F10 melanoma cells) killing. Melanoma-bearing mice treated intratumorally with DOX (8 µg)-loaded microspheres and subjected to US treatment at the tumor site were shown to significantly extended survival compared to untreated mice or mice subjected to either treatment alone. The synergistic increase in survival of melanoma-challenged mice treated with the combination of US and DOX-loaded microspheres implicates a promising additional tool for combatting an otherwise currently incurable cancer. We then further investigated other novel control drug delivery systems which included a 3D printed device (tube) for the purposes of sequential drug delivery. 3D printed hollow alginate tubes were fabricated through co-axial bioprinting and then injected with PLGA to provide sequential release of distinct fluorescent dyes (model drugs), where fluorescein was initially released from alginate followed by the delayed release (up to 55 h) of rhodamine B in PLGA. With an alginate shell and a PLGA core, the fabricated tubes showed no cytotoxicity when incubated with the human embryonic kidney (HEK293) cell line or bone marrow stromal stem cells (BMSC). Microscale printing through two-photon polymerization (2PP) was then investigated for controlled drug delivery potential. Poly(ethylene glycol) dimethacrylate (PEGDMA) devices were fabricated using a Photonic Professional GT two-photon polymerization system while rhodamine B was homogenously entrapped inside the polymer matrix during photopolymerization. These devices were printed with varying porosity and morphology and using varying printing parameters such as slicing and hatching distance. Overall, tuning the hatching distance, slicing distance, and pore size of the fabricated devices provided control of rhodamine B release due to resulting changes in the motility of the small molecule and its access to structure edges. In general, increased spacing provided higher drug release while smaller spacing resulted in some occlusion, preventing media infiltration and thus resulting in reduced drug release. 2PP was further explored for its ability to tailor topographical cues in addition to controlled drug release. These physical cues, similar to those of the ECM, have been seen to promote differentiation. With 2PP, we explored microscale topographies with nanoscale precision, where different star size topographies were fabricated. It was observed that the smallest star size topographies differentiated human iPSCs towards the endoderm and mesoderm germ layer. Integrating the facility for controlled drug release into 3D printed devices provides a demand for constructs that not only need to fulfill their purpose of temporarily substituting for the missing tissue at the site of injury, but also providing the necessary cues to promote appropriate tissue regeneration. With 3D printing technology, novel drug delivery constructs were fabricated and tested to appraise functionality such as the ability to control drug delivery and the ability to function as a non-toxic medium for cellular attachment, proliferation, and forced differentiation.

Page generated in 0.062 seconds