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Dawson, Jennifer Elizabeth. "Cardiac Tissue Engineering." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20071.
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The limited treatment options available for heart disease patients has lead to increased interest in the development of embryonic stem cell (ESC) therapies to replace heart muscle. The challenges of developing usable ESC therapeutic strategies are associated with the limited ability to obtain a pure, defined population of differentiated cardiomyocytes, and the design of in vivo cell delivery platforms to minimize cardiomyocyte loss. These challenges were addressed in Chapter 2 by designing a cardiomyocyte selectable progenitor cell line that permitted evaluation of a collagen-based scaffold for its ability to sustain stem cell-derived cardiomyocyte function (“A P19 Cardiac Cell Line as a Model for Evaluating Cardiac Tissue Engineering Biomaterials”). P19 cells enriched for cardiomyocytes were viable on a transglutaminase cross-linked collagen scaffold, and maintained their cardiomyocyte contractile phenotype in vitro while growing on the scaffold. The potential for a novel cell-surface marker to purify cardiomyocytes within ESC cultures was evaluated in Chapter 3, “Dihydropyridine Receptor (DHP-R) Surface Marker Enrichment of ES-derived Cardiomyocytes”. DHP-R is demonstrated to be upregulated at the protein and RNA transcript level during cardiomyogenesis. DHP-R positive mouse ES cells were fluorescent activated cell sorted, and the DHP-R positive cultured cells were enriched for cardiomyocytes compared to the DHP-R negative population. Finally, in Chapter 4, mouse ESCs were characterized while growing on a clinically approved collagen I/III-based scaffold modified with the RGD integrin-binding motif, (“Collagen (+RGD and –RGD) scaffolds support cardiomyogenesis after aggregation of mouse embryonic stem cells”). The collagen I/III RGD+ and RGD- scaffolds sustained ESC-derived cardiomyocyte growth and function. Notably, no significant differences in cell survival, cardiac phenotype, and cardiomyocyte function were detected with the addition of the RGD domain to the collagen scaffold. Thus, in summary, these three studies have resulted in the identification of a potential cell surface marker for ESC-derived cardiomyocyte purification, and prove that collagen-based scaffolds can sustain ES-cardiomyocyte growth and function. This has set the framework for further studies that will move the field closer to obtaining a safe and effective delivery strategy for transplanting ESCs onto human hearts.
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Somasundaram, Murali. "Intestinal tissue engineering." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:54e0f17f-fe04-4012-b0d3-04f436e9af9a.
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Tissue engineering (TE) principles have been successfully clinically applied to treat disease affecting specific organs (e.g. trachea) but developments in some organs has lagged behind. The inability to repair or replace significantly damaged intestinal tissue remains a barrier to improving patient outcomes and the promise of Tissue Engineered Intestine (TEI) that was first made more than 20 years ago, is yet to be realised. This work explored the potential of TEI and literature review formed a basis for developing a clinically transferrable experimental model. It was hypothesised that, porcine large intestine could be retrieved from pigs and decellularized to create a biological scaffold that demonstrated favourable properties for TE, including potential for vascular perfusion and cell engraftment. Novel experiments were performed in intestinal retrieval and decellularization, resulting in scaffolds characterised by a number of methods (e.g. histology, immunohistochemistry). Assessment of the scaffold's ability to support cell engraftment required development of protocols for isolation and culture of appropriate progenitors, including adipose/bone marrow derived mesenchymal stromal cells and intestinal organoid units. Finally, in-vitro cultures combining scaffolds and cells were used to assess the ability of scaffolds to promote tissue regeneration. Perfusion decellularization methods proved effective in creating biological scaffolds that retained radiologically demonstrated vascular perfusion networks, permitting a future route for recellularization and/or transplantation. Scaffolds demonstrated retention of essential extracellular matrix components (e.g. glycosaminoglycans, collagen) and an absence of cell nuclei. Mesenchymal stem cells were isolated, cultured and combined in-vitro with scaffolds in an attempted scaled-down seeding model. Control of culture conditions was challenging and results inconclusive with respect to the scaffold's regenerative potential. The work demonstrates an exciting prospect for biological scaffold development for a clinically transferrable, semi-xenogeneic transplant or drug delivery model but further experiments in scaffold seeding are required to assess the full potential.
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BERNOCCO, MARCO. "Bioreactor engineering for tissue engineering application." Doctoral thesis, Politecnico di Torino, 2013. http://hdl.handle.net/11583/2513796.
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Lo scopo di questo lavoro di tesi è la caratterizzazione metrologica di un bioreattore con l’intento di aumentare la riproducibilità e l’affidabilità dei processi di Ingegneria tessutale (Tissue Engineering, TE). La Tissue engineering (TE) o ingegneria dei tessuti è la disciplina che studia la comprensione dei principi della crescita dei tessuti, e la loro applicazione per produrre tessuto funzionale per uso clinico o diagnostico. Uno dei principali scopi della TE è l’impiego di tessuti in crescita naturale extracorporea per la medicina rigenerativa, in altre parole lo sviluppo di strategie terapeutiche mirate alla sostituzione, riparazione, manutenzione e/o il miglioramento della funzione dei tessuti. L’ingegneria dei tessuti è caratterizzata da una grande interdisciplinarità che prevede la collaborazione di figure professionali con competenze molto differenti tra loro, quali biologi, chimici, fisici, matematici, ingegneri.
L’obiettivo è il progetto di un bioreattore che sia affidabile e controllabile per seguire l’evoluzione del processo. Questo deve essere eseguito applicando metodi metrologici allo studio del processo. La metrologia permette di poter quantificare l’incertezza di un fenomeno quindi di determinare la proprietà di un fenomeno, corpo o sostanza, che può essere distinta qualitativamente e determinata quantitativamente. Le fonti d’incertezza che caratterizzano l’incertezza finale o composta è legata: alla mancanza di conoscenza e alla variabilità del sistema e prevede strategie differenti per la loro gestione. La mancanza di conoscenza e può essere ridotta migliorando le informazioni sul sistema in esame, mentre la variabilità del sistema sotto studio, può essere gestita riducendo degli scenari presi in considerazione o definendo più precisamente il sistema studiato.
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Rouwkema, Jeroen. "Prevascularized bone tissue engineering." Enschede : University of Twente [Host], 2007. http://doc.utwente.nl/57929.
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Mirsadraee, Saeed. "Tissue engineering of pericardium." Thesis, University of Leeds, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426783.
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Getgood, Alan Martin John. "Articular cartilage tissue engineering." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608764.
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Tseng, Yuan-Tsan. "Heart valve tissue engineering." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:e67c780d-d60f-42e7-9311-dd523f9141b3.
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Since current prosthetic heart valve replacements are costly, cause medical complications, and lack the ability to regenerate, tissue-engineered heart valves are an attractive alternative. These could provide an unlimited supply of immunological-tolerated biological substitutes, which respond to patients' physiological condition and grow with them. Since collagen is a major extra cellular matrix component of the heart valve, it is ideal material for constructing scaffolds. Collagen sources have been shown to influence the manufacturing of collagen scaffolds, and two commercial sources of collagen were obtained from Sigma Aldrich and Devro PLC for comparison. Consistencies between the collagens were shown in the primary and secondary structures of the collagen, while inconsistencies were shown at the tertiary level, when a higher level of natural crosslinking in the Sigma collagen and longer polymer chains in the Devro collagen were observed. These variations were reduced and the consistency increased by introducing crosslinking via dehydrothermal treatment (DHT). Collagen scaffolds produced via freeze-drying (FD) and critical point-drying with cross-linking via DHT or 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide /N-hydroxysuccinimide (EDC/NHS) were investigated. All the scaffolds were compatible with mesenchymal stem cells (MSCs) according to the proliferation of the cells and their ability to produce ECM, without differentiating between osteogenic, chondrogenic or endothelial lineages. The FD EDC/NHS scaffold demonstrated the most suitable physical property of all. This result illustrates that FD EDC/NHS crosslinking is the most suitable scaffold investigated as a start for heart valve tissue engineering. To prepare a scaffold with a controlled local, spatial and temporal delivery of growth factor, a composite scaffold comprising poly (lactic-co-glycolic acid) (PLGA) microspheres was developed. This composite scaffold demonstrated the same compatibility to the MSCs as untreated scaffold. However, the PLGA microspheres showed an increase in the deterioration rate of Young's modulus because of the detachment of the microspheres from the scaffold via cellular degradation.
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Aor, Bruno. "Engineering microchannels for vascularization in bone tissue engineering." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0430/document.
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In vitro, la formation de structures de type tubulaire avec des cellules endothéliales de veine ombilicale humaine (HUVEC) a été étudiée en combinant la fonctionnalisation de la chimie des matériaux et le développement de la géométrie tridimensionnelle. Le polycarbonate (PC) a été utilisé comme modèle pour le développement de l'échafaud. Le film de polysaccharide naturel, basé sur un dépôt alternatif couche par couche (LbL) d’acide hyaluronique (HA) et de chitosane (CHI), a d’abord été appliqué sur une surface PC et caractérisé en termes de croissance d’épaisseur microscopie à balayage lascar (CLSM). Cette première fonctionnalisation se traduit par un revêtement complet de la couche PC. Une biofonctionnalisation supplémentaire avec un peptide adhésif (RGD) et deux peptides angiogénétiques (SVV et QK) a été étudiée, immobilisant ces peptides sur le groupe carboxylique de HA précédemment déposé, en utilisant la chimie bien connue du carbodiimide. La version marquée de chaque peptide a été utilisée pour caractériser l’immobilisation et la pénétration des peptides dans les couches de polyélectrolytes, aboutissant à une greffe réussie avec une pénétration complète dans toute l’épaisseur du LbL. Des tests in vitro ont été effectués à l'aide de cellules HUVEC pour évaluer leur efficacité d'adhésion et leur activité métabolique sur la LbL avec et sans immobilisation de peptides, ce qui a permis d'améliorer l'activité préliminaire lorsque des combinaisons de peptides sont utilisées. Enfin, les micro-canaux PC (μCh) ont été développés et caractérisés pour la première fois, et les autres expériences ont été réalisées sur un micromètre de 25 μm de largeur, fonctionnalisé avec une architecture (HA / CHI) 12,5 (PC-LbL) avec des peptides RGD et QK -RGD + QK) ou avec des peptides RGD et SVV (PC-RGD + SVV). Notre première expérience de tubulogénèse a montré de manière surprenante la formation de structures de type tubulaire déjà après 2h d'incubation en utilisant la combinaison double-peptides, mais uniquement avec PC-RGD + QK. Les tubes étaient également présents après 3 et 4 heures de culture. L'expérience de co-culture avec des péricytes humains dérivés du placenta (hPC-PL) montre comment la stabilisation des tubes a été améliorée après 3 et 4 heures également pour l'échantillon de PC-RGD + SVV. Globalement, notre matériel bio-fonctionnel avec les peptides PC-RGD + QK et PC-RGD + SVV permet la formation d'une structure de type tubulaire à la fois dans une expérience de monoculture et de co-cultureIn vitro, tubular-like structures formation with human umbilical vein endothelial cells (HUVECs) was investigated by combining material chemistry functionalization and three-dimensional geometry development. Polycarbonate (PC) was used as a template for the development of the scaffold. Natural polysaccharide’s film based on alternate layer-by-layer (LbL) deposition of hyaluronic acid (HA) and chitosan (CHI), was first applied to PC surface and characterized in terms of thickness growth both, in dry conditions using ellipsometry, and confocal lascar scanning microscopy (CLSM). This first functionalization results in a complete coating of the PC layer. Further biofunctionalization with one adhesive peptide (RGD) and two angiogenetic peptides (SVV and QK) was investigated, immobilizing those peptides on the carboxylic group of HA previously deposited, using the well-known carbodiimide chemistry. The labeled version of each peptide was used to characterize the peptides’ immobilization and penetration into the polyelectrolytes layers, resulting in a successful grafting with complete penetration through the entire thickness of the LbL. In vitro tests were performed using HUVECs to assess their adhesion efficiency and their metabolic activity on the LbL with and without peptide immobilization, resulting in a preliminary improved activity when peptide-combinations is used. Finally, PC micro-channels (μCh) were first developed and characterized, and the rest of the experiments were performed on μCh of 25μm width, functionalized with (HA/CHI)12.5 architecture (PC-LbL) with RGD and QK peptides (PC-RGD+QK) or with RGD and SVV peptides (PC-RGD+SVV). Our first tubulogenesis experiment surprisingly showed the formation of tubular-like structures already after 2h of incubation using the double-peptides combination but only using PC-RGD+QK the tubes were present also after 3 and 4 hours of culture. The co-culture experiment with human pericytes derived from placenta (hPC-PL) demonstrates how the stabilization of the tubes was improved after 3 and 4 hours also for the PC-RGD+SVV sample. Globally our bio-functional material with PC-RGD+QK and PC-RGD+SVV peptides allow the formation of tubular-like structure in both mono and co-culture experiment
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Sodian, Ralf. "Tissue-Engineering von kardiovaskulären Geweben." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=974660175.
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Kamei, Yuzuru, Kazuhiro Toriyama, Toru Takada, and Shunjiro Yagi. "Tissue-Engineering Bone from Omentum." Nagoya University School of Medicine, 2010. http://hdl.handle.net/2237/14172.
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Czechura, Pawel. "Saturated neoglycopolymers for tissue engineering." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27121.
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Norbornene monomers bearing carbohydrate groups of relevance for tissue engineering were synthesized via the norbornene acid chlorides, transformed into their ROMP polymers, and reduced to yield saturated neoglycopolymers. These materials bear either O-glycoside groups designed to cross-link collagen via reaction of the ring-open sugar with free NH2 groups of lysine, or C-glycoside groups. The latter are intended for use as the central block in triblock copolymers terminated with blocks capable of crosslinking: they serve only as potentially biocompatible "spacers" to help span the interlamellar distance in collagen. A third ROMP monomer bearing a succinimide group as an alternative crosslinking agent was also prepared and polymerized. The O-glycoside monomer, bis(1,2;3,4-di-O-isopropylidene-D-galactopyranos-6-O-yl) 5-norbornene-2,3-dicarboxylate 9, and the succinimide monomer, 5-norbornene-2-carboxylic acid N-hydroxysuccinimide ester 11, were prepared by the Diels-Alder synthesis of 5-norbornene-2,3-dicarbonyl chloride 7 and 5-norbornene-2-carboxylic acid chloride 8, and subsequent nucleophilic substitution of the acid chlorides. (Abstract shortened by UMI.)
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Hussain, Timon. "Tissue Engineering mit porösen Polyethylenimplantaten." Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-162027.
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Hintergrund: Eine Verbesserung der Biokompatibilität von porösen Polyethylenimplantaten könnte postoperative Komplikationsraten senken und das klinisches Anwendungsgebiet des Biomaterials erweitern. Im Rahmen dieser Studie wurde untersucht, ob eine „Vitalisierung“ von porösen Polyethylenimplantaten mit dermalen Fibroblasten möglich ist und ob hierdurch die mikrovaskuläre Integration sowie die immunologische Reaktion des Wirtsorganismus beeinflusst werden konnte.
Material und Methoden: Poröse Polyethylenimplantate wurden in vitro mit GFP-markierten dermalen Fibroblasten kultiviert. Die auf dem Biomaterial adhärenten Zellen wurden vor Implantation in dorsale Rückenhautkammern an C57/Bl6 Mäusen mittels konfokaler Mikroskopie quantifiziert, ebenso nach Explantation. Native Implantate dienten als Kontrolle. Angiogeneseprozesse sowie die Leukozyten-Endothelzellinteraktion im Implantatmaterial wurden wiederholt mittels in vivo Fluoreszenzmikroskopie analysiert. Abschließend wurde die dynamische Desintegrationskraft quantifiziert und eine Analyse immunmodulatorischer Zytokine durchgeführt.
Ergebnisse: Poröse Polyethylenimplantate konnten nachhaltig mit dermalen Fibroblasten „vitalisiert“ werden. Mikrozirkulatorische Parameter nahmen während des Beobachtungszeitraums zu, allerdings konnten keine signifikanten Unterschiede zwischen den Gruppen festgestellt werden. Einzelne immunmodulatorische Zytokine waren in „vitalisierten“ porösen Polyethylenimplantaten tendenziell erhöht, eine signifikante Beeinflussung der Immunantwort des Wirtsorganismus war jedoch nicht festzustellen.
Schlussfolgerung: Eine „Vitalisierung“ von porösen Polyethylenimplantaten mit dermalen Fibroblasten ist nachhaltig durchführbar, beeinflusst jedoch die mikrovaskuläre Integration in vivo sowie die Immunreaktion des Wirtsorganismus nicht signifikant. Somit sind möglicherweise zusätzliche Maßnahmen im Sinne eines Tissue Engineerings erforderlich, um die Biokompatibilität von porösen Polyethylenimplantaten mittels dieser vielversprechenden Zellquelle zu verbessern.
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Cooper, Leanne Jane. "Tissue engineering of the cornea." Thesis, Lancaster University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421611.
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Wung, Nelly. "Tissue engineering of the liver." Thesis, University of Bath, 2017. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715264.
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Currently, the only cure for liver failure is orthotopic liver transplantation. However, there are insufficient donor organs available to treat every patient on the transplant list and many die before they are able to receive a liver transplant. The bioartificial liver (BAL) device is a potential extracorporeal treatment strategy utilising hepatocytes or hepatocyte-like cells (HLCs) within a bioreactor to recapitulate normal liver function and therefore ‘bridge’ a patient with liver failure until they receive a transplant. The work in this thesis utilised tissue engineering methods to develop novel approaches to BAL device design through development and characterisation of a polymer membrane scaffold (“PX”) for hollow fibre bioreactor (HFB) culture and a HLC source generated from the transdifferentiation of pancreatic AR42J-B13 (B13) cells. A flat sheet membrane model was used for the development of asymmetrical, hydrophobic polystyrene (PS) phase inversion membranes. Oxygen plasma significantly increased PS membrane surface wettability through addition of oxygen functional groups to create an environment conducive for cell culture. The treated membrane was henceforth referred to as “PX”. The culture medium HepatoZYME+ was investigated for its ability to induce transdifferentiation of B13 cells to HLCs and maintain the hepatic phenotype. Overall, HepatoZYME+-cultured cells experienced viability loss. A diluted version, “50:50”, showed induction of the hepatic markers carbamoylphosphate synthetase-1 (CPS-1) and HNF4α, as well as a change towards a HLC morphology. When using 50:50 as a maintenance medium, transdifferentiated HLCs retained loss of pancreatic amylase and also induction of hepatic markers, with comparable serum albumin secretion to the established Dex + OSM treatment. However, culture viability in 50:50 was still compromised. Therefore, HepatoZYME+ based media were deemed unsuitable for induction and maintenance compared to Dex-based protocols. PX flat sheet membranes were able to support culture of B13 cells and also the human osteosarcoma cell line, MG63, demonstrating improved cell attachment over non-surface treated PS membranes. PX membranes supported transdifferentiation of B13 cells to HLCs, presenting with loss of pancreatic amylase, induction of the hepatic markers transferrin, GS and CPS-1 and serum albumin secretion. Furthermore, PX showed no change in mass or loss of culture surface area over 15 days in culture conditions. Together, the novel membrane material and the media formulation and feeding regime developed have strong potential to be translated to a HFB setting and guide future BAL device design.
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Mehrban, Nazia. "Tissue engineering a ligamentous construct." Thesis, University of Birmingham, 2011. http://etheses.bham.ac.uk//id/eprint/2989/.
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Tendon and ligament damage causes extreme pain and decreased joint functionality. Current repair methods cannot restore original joint biomechanics nor promote regeneration of native tissue. Recent advances in tendon and ligament repair have involved engineering tissue using cell-seeded scaffolds. Self-aligned cellular structures, similar to those in ligaments and tendons, have been successfully formed, albeit with weak attachment between construct and bone. Calcium phosphates form an intimate bond with both soft and hard tissues and have successfully been used in tissue engineering bone, whilst hydrogels have often been used as cellular scaffolds. This thesis explores agarose, gelatin, carrageenan and fibrin hydrogels as potential soft tissue scaffolds. Fibrin gel exhibited high cellular compatibility with highest metabolic activity on day 14. Although the cellular gel contracted significantly, it was found that the dry weight remained stable in both the acellular and cellular forms. 3D powder printed calcium phosphate scaffolds remained structurally stable after immersion in cell culture media with immersion in protein-rich sera promoting tenocyte attachment. Bracket designs were developed to enhance grip of the cell-seeded fibrin. Ligament constructs were selfsupporting and exhibited structural characteristics similar to native connective tissue. Tenocyte density peaked on day 14, with added L-proline and ascorbic acid inducing a constant level of glycosaminoglycans and 7.4 ± 1.5 % w/w collagen. This research may significantly enhance the clinical application of tissue engineered ligaments and tendons.
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Schrader, S. "Tissue engineering for conjunctival reconstruction." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1348133/.
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Reconstruction of the conjunctiva is an essential part of ocular surface regeneration, especially if an extensive area or the whole ocular surface is affected, such as in patients with ocular cicatricial pemphigoid, Stevens- Johnson syndrome or chemical/thermal burns. However, there is a lack of suitable donor tissue for conjunctival replacement, especially when large grafts are required and it is important that new materials and methods are developed for conjunctival reconstruction. The aims of this thesis were; to characterise the conjunctival epithelial cell population and to improve the maintenance of the epithelial progenitor cells during in vitro expansion in order to produce conjunctival epithelial cells suitable for therapeutic use. The final aim was to transfer these cells to compressed collagen matrices and amniotic membrane and test the properties of these cell-matrix constructs. Experiments showed that cryopreservation does not to alter the proliferative potential of conjunctival epithelial progenitor cells. It was also demonstrated that the maintenance of conjunctival epithelial progenitor cells during cell expansion can be improved by mimicking an environment in vitro, which is more similar to the stem cell niche in vivo and that this is accompanied by downregulation of key genes in the wnt signaling pathway. The final experimental series showed that after in vitro expansion, conjunctival epithelial cells can be successfully transferred and cultured on amniotic membrane and compressed collagen gels. In conclusion these studies highlighted the complexity of tissue engineering ocular surface substitutes and provided further clues for the goal to obtain a stable conjunctival substitute, suitable for transplantation.
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Qiu, Yiwei. "In vitro tendon tissue engineering." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:10d2b8fe-c485-44e4-ba03-abdad0da48f7.
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Tendon, ligament, and joint capsular injuries represent 45% of the 32 million musculoskeletal injuries each year in the United States. Tendon injuries are especially common, requiring surgical repair for the shoulder’s rotator cuff tendons (51,000 per year), the Achilles tendon (44,000 per year), and the patellar tendon (42,000 per year). Tissue engineering provides an alternative in the treatment of tendon lesions through replacement of an injured tendon segment. The purpose of this study was to develop a tendon construct in vitro for clinical reconstructive surgery. Human tenocytes were isolated from hamstring tendons of patients who had undergone anterior cruciate ligament (ACL) surgeries. These tenocytes were cultured with culture media (α-MEM) supplemented with various concentrations of foetal bovine serum (FBS) (0%, 1%, 5% and 10%) and in the presence of different growth factors such as PDGFBB (0, 5, 10 and 50ng/ml), basic FGF (0, 5, 10 and 50ng/ml), IGF-1 (0, 10 and 50ng/ml) and TGFβ-3 (0, 1 and 10ng/ml). Fractional factorial design was utilized to select the combinations of growth factors that supported the following criteria: (1) the maximal cell proliferation with a minimum differentiation of the tenocytes in the presence of the least concentration of FBS possible and (2) maintaining cell survival and promoting tenocyte differentiation in FBS free culture media. The results have shown that: (i) The tenocyte cell number when cultured for 14 days in media supplemented with 1% FBS, 50ng/ml PDGFBB and 50ng/ml bFGF matched that of the positive control (10% FBS-treated cells). Not only was the collagen synthesis significantly reduced in these growth factor-treated cultures compared to positive control tenocytes, but also a significant inhibition of the mRNA expression of various tenocyte differentiation markers (Scleraxis, Tenomodulin, Collagen type I and Decorin) was evident. IGF-1 did not promote significant cell proliferation under low serum conditions but did induce tenocyte differentiation in vitro. Examination of the cell morphology confirmed that tenocytes were capable of less differentiation when cultured with 1% FBS, 50ng/ml PDGFBB and 50ng/ml bFGF, this culture condition was termed “the expansion phase”; (ii) The cell survival was maintained for up to 14 days in serum free culture media supplemented with 50ng/ml IGF-1 and 10ng/ml TGFβ-3 whilst cell differentiation was enhanced and evident by the increase in collagen synthesis and cell morphology. Furthermore, mRNA expression of the aforementioned cell differentiation markers were also significantly increased, this culture condition was termed “the differentiation phase”; (iii) By combining the culture condition optimized for the expansion and differentiation phase sequentially, it was possible to maintain a long term 2-D tenocyte culture in vitro for up to 28 days. In these cultures, the presence of dense collagen formation was clearly evident whereas in positive control group (10% FBS group) such observation was not noted even after prolonged culturing period of up to 45 days. These results suggested that the sequential treatment of tenocytes with growth factors identified for the expansion and differentiation phases was significantly more superior than the standard 10% FBS treatment; (iv) By combining the expansion and differentiation phases optimized for the 2-D cultures, it was possible to maintain human tenocytes in a 3-D scaffold (Bombix silk) for up to 28 days. The tendon like constructs that were formed, macroscopically and microscopically resembled the human hamstring tendon. This observation was confirmed by using H&E staining, scanning electron microscopy and by detecting collagen type I immunohistochemically; (v) It was possible to further validate these findings using in vivo animal models. This was undertaken by implanting the tenocytes cultured sequentially in the defined culture media described above, into the quadriceps of Balb/c nude male mice for up to 30 days. The nature and specificity of the tendon like structure that was formed after this implantation was investigated by H&E staining and immunohistochemistry. It was revealed that the culture conditions that were optimized during the expansion and differentiation phases were suitable for generating a human tendon reconstruct; a finding which is of significance due to its potential for tendon reconstructive surgery.
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Muhamad, Farina. "Electrospun scaffolds for tissue engineering." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/14577.
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A critical challenge in designing materials for tissue engineering (TE) is to provide essential cues that can control cellular behaviour and promote tissue regeneration. TE with fibrous scaffolds by using electrospinning is emerging as a major research area in the field of regenerative medicine. This thesis presents the development of novel electrospun fibrous acrylate scaffolds for bone TE. Acrylate fibrous scaffolds were developed by electrospinning photocrosslinkable and low molecular weight acrylate monomers, methyl acrylate (MA) and diethylene-glycol dimethacrylate (DEGMA). Photocrosslinked fibres were successfully produced by electrospinning different MA and DEGMA compositions and post-UV crosslinking. The ability to produce topologically and mechanically diverse fibrous scaffold materials was demonstrated. Varying MA and DEGMA composition affected overall fibre morphology, swelling and mechanics of the fibrous scaffold. An assessment of biological activity of the acrylate fibrous scaffold was performed to evaluate the effect of varying ratios of MA/DEGMA of the fibrous scaffold on the viability of two different cell types, osteosarcoma-derived osteoblastic cells (Saos-2) and mesenchymal stromal cells (hMSCs). The potential of MA/DEGMA fibrous scaffolds to support Saos-2 cell viability and proliferation was demonstrated. However, the considerable increase in apoptosis of hMSCs cultured on both fibrous and flat samples suggested a lower potential of the MA/DEGMA scaffolds to support hMSCs cell attachment and viability. The fibrous scaffolds were immobilized with synthetic peptides utilizing cysteine-functionalized RGD or DGEA peptide sequences in combination with MA/DEGMA monomers and by employing a photoinitiated mixed-mode thiol-acrylate polymerization mechanism. Cysteine-functionalized DGEA and RGD peptides were incorporated efficiently in the synthesized acrylate scaffold. The peptide-conjugated fibrous scaffolds showed increased hMSCs adhesion and viability. Through cell adhesion and soluble peptide competition assays, the bioactivity and specificity of each peptide conjugated to the scaffold was confirmed. Finally, hMSCs cultured on DGEA conjugated scaffolds exhibited the activation of osteogenic differentiation markers, alkaline phosphatase (ALP) and osteocalcin (OCN). The results presented in this thesis strongly suggest the potential of the acrylate fibrous scaffold for bone TE.
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Place, Elsie Sarah. "Bioactive hydrogels for tissue engineering." Thesis, Imperial College London, 2011. http://hdl.handle.net/10044/1/7106.
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Modern tissue engineering (TE) scaffolds are expected to actively promote tissue repair as well as meeting the traditional requirements of non-toxicity, degradability and structural integrity. This thesis presents two novel bioactive hydrogel systems for bone and cartilage TE. A series of alginate hydrogels were developed in which all or a fraction of the calcium normally used for crosslinking alginate was replaced by bioactive strontium and/or zinc ions. Strontium was chosen for its ability to stimulate bone formation, while zinc is essential for alkaline phosphatase activity. Due to an interaction between the crosslinking ion and alginate type, the hydrogel properties could be tailored independently of the crosslinking ion used – meaning that varying biological and materials requirements can be accommodated. Strontium release from alginate gels was of a physiologically relevant magnitude, and alkaline phosphatase protein activity in Saos-2 cells was highest in strontium gels. Secondly, a biomimetic strategy for transforming growth factor beta (TGF-β) presentation and release was evaluated. TGF-β in vivo is secreted as part of an inactive latent complex, which is sequestered in a stable form within extracellular matrix until released by cells. TGF-β was therefore incorporated into poly(ethylene glycol)-hyaluronic acid hydrogels in its latent form. When compared to free TGF-β, advantages were demonstrated in terms of lower protein adsorption to tissue culture plastic and relative biological inactivity. The latter implies that high doses may be loaded into TE scaffolds without exposing cells to excessive quantities of active growth factor, with TGF-β bioavailability then being controlled by gradual activation by cells. Increased metabolic activity and ECM deposition by bovine chondrocytes were seen after almost five weeks in culture with a single initial loading of LTGF-β. These innovations correspond to current TE trends, which seek to use biomimetic principles to evoke regenerative responses from transplanted or host cells, but to do so using technically and commercially feasible means.
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Sodian, Ralf. "Tissue Engineering von kardiovaskulären Geweben." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2005. http://dx.doi.org/10.18452/13965.
Full textAbstract:
Beim Tissue Engineering werden Erkenntnisse aus der Medizin, Biologie und Chemie mit Methoden der Ingenieurwissenschaften kombiniert, um biologische Ersatzgewebe herzustellen. Das Konzept besteht darin, aus körpereigenen Zellen einen vitalen und funktionalen Gewebeersatz zu fertigen. Hierbei werden körpereigene Zellen auf ein resorbierbares Gerüst transplantiert, in vitro zu einer stabilen Struktur gefestigt, um letztendlich ein vitales Ersatzgewebe implantieren zu können. Die Konstrukte für die menschliche Herzchirurgie sollten in das umgebende Gewebe einwachsen und haben das Potential sich wie gesundes Gewebe zu entwickeln und mitzuwachsen.Tissue engineering combines knowledge from the fields of medicine, biology and chemistry with the methods of engineering to create artificial tissue. The concept is to produce vital and functional tissue from endogenous cells. These are seeded on to an absorbable scaffold and consolidated to form a stable structure in vitro, with the aim of eventually being able to produce substitute tissue for implantation. The constructs for human cardiac surgery need to embed into the surrounding tissue and, just like natural tissue, to have the potential to grow and develop.
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SCARPA, TOMMASO. "BIOPOLYMERS FOR CARTILAGE TISSUE-ENGINEERING." Doctoral thesis, Università degli studi di Trieste, 2007. http://thesis2.sba.units.it/store/handle/item/12302.
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FACCENDINI, ANGELA. "NANOCOMPOSITE SCAFFOLDS FOR TISSUE ENGINEERING." Doctoral thesis, Università degli studi di Pavia, 2021. http://hdl.handle.net/11571/1447787.
Full textAbstract:
Lo scopo del progetto è stata la progettazione e lo sviluppo di scaffold elettrofilati ibridi a base di polisaccaridi e glicosaminoglicani con particelle minerali incluse nella matrice nanofibrosa. Gli scaffold sono stati destinati all'ingegneria dei tessuti dermici o tendinei. Gli scaffold dermici sono stati caricati con montmorillonite o alloisite, come dispositivi medici. Inoltre, sono stati sviluppati scaffold caricati con un nanocomposito di norfloxacina-montmorillonite per trattare e prevenire le infezioni delle ferite.
Sono stati sviluppati anche scaffold tubolari, come impianto nella chirurgia dei tendini. Tali scaffold sono costituiti da nanofibre allineate lungo la lunghezza della struttura e caricati con nanoparticelle di idrossiapatite, oppure sono costituiti da una struttura che presenta un gradiente in nanoparticelle di idrossiapatite, in una parte nanofibrosa, come estremità ossea, e da una struttuta nanofibrosa allineata, come estremità del tendine, con lo scopo specifico di riparare l'interfaccia tendine-osso. Il lisato piastrinico o il condroitin solfato e le cellule staminali adipose, sono stati caricati nei due tipi di scaffold per migliorare il processo di guarigione delle lesioni tendinee.The aim of the project was the design and the development of hybrid electrospun scaffolds based on polysaccharides and glycosaminoglycans. Mineral particles were included in the nanofibrous matrix. The scaffolds were intended for dermal or tendon tissue engineering. Dermal scaffolds were loaded with montmorillonite or halloysite, as medical devices. Moreover, scaffolds loaded with norfloxacin-montmorillonite nanocomposite were developed to treat and prevent wound infections. Furthermore, tubular scaffolds, as implants in tendon surgery were developed. They were made of nanofibers aligned along scaffold length, and loaded with hydroxyapatite nanoparticles, or are made of a tubular scaffold based on a gradient in hydroxyapatite nanoparticles, in a random nanofibrous part, as bone end, and on an aligned nanofibrous scaffolds, as tendon end, and this latter is specifically intended to repair the tendon to bone interface. Platelet lysate or chondroitin sulfate and adipose stem cells were loaded in the two scaffold types to enhance the wound healing process.
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RIVA, LEONARDO. "Biomanufacturing Technologies for Tissue Engineering." Doctoral thesis, Università degli studi di Brescia, 2023. https://hdl.handle.net/11379/571155.
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Il seguente lavoro di tesi ha come obiettivo lo studio e la realizzazione di device biomedicali realizzati tramite la manifattura additiva. La manifattura additiva sta avendo una forte crescita negli ultimi anni grazie soprattutto alla possibilità di realizzare facilmente geometrie complesse. Questa caratteristica permette di personalizzare i prodotti ad un costo competitivo. Inoltre, lo spreco di materiale viene ridotto moltissimo dal principio di fabbricazione. Tutte queste proprietà hanno fatto in modo che negli ultimi anni la manifattura additiva prendesse sempre più piede in campi come l’automotive, l’aerospace e il biomedicale.
Questo lavoro di tesi è focalizzato sull’utilizzo di alcune tra le più diffuse tecnologie additive per la produzione di device biomedicali. In particolare, il lavoro si è concentrato principalmente sulla realizzazione di due modelli, il primo per lo studio dello sviluppo dei black floaters all’interno del corpo vitreo dell’occhio, il secondo per l’emulazione del comportamento dell’osso mandibolare durante la foratura per l’installazione di impianti dentali.
Il modello dell’occhio è composto da due elementi principali, un supporto e un hydrogel. Il supporto serve a contenere e supportare l’hydrogel. Deve essere trasparente, biocompatibile facilmente manovrabile in laboratorio. La sua realizzazione è avvenuta tramite stereolitografia. L’hydrogel, invece, ha lo scopo di fornire un’ambiente 3D per la crescita e sviluppo delle cellule. Deve perciò anche lui essere biocompatibile e con adeguate caratteristiche meccaniche e di stampabilità. La struttura 3D è stata realizzata tramite material extrusion.
Il modello di osso mandibolare è stato realizzato tramite fused filament fabrication. Il modello si compone di due parti, una parte esterna piena per emulare l’osso corticale, e una parte interna porosa per emulare l’osso trabecolare. Le prove di foratura sono state realizzate con un trapano dentistico agganciato a robot collaborativi.
La ricerca ha infine toccato ulteriori due ambiti, lo studio delle proprietà di strutture lattice realizzate tramite laser based- powder bed fusion e la valutazione di diversi trattamenti di finitura superficiale.
La tesi, dunque, ha la seguente organizzazione. Il capitolo 1 presenta un’introduzione sull’additive manufacturing e il bioprinting. Le tecnologie ed i materiali utilizzati sono brevemente descritti e sono riportati alcuni esempi di applicazione della manifattura additiva nel campo biomedicale. I capitoli seguenti, invece, riportano gli articoli pubblicati o in corso di pubblicazione riguardo alle diverse tematiche affrontate. Nello specifico, il capitolo 2 riporta la ricerca sulle strutture lattice e la loro realizzazione. I capitoli 3 e 4 comprendono gli studi relativi al modello dell’occhio. Il capitolo 3 si concentra sulla realizzazione del supporto, il 4 sulla formulazione e la valutazione dell’hydrogel. Il capitolo 5 approfondisce lo studio del modello per l’emulazione del comportamento dell’osso mandibolare a foratura mentre il capitolo 6, l’ultimo di questo elaborato, si concentra sui processi di finitura superficiale.
Per concludere, la manifattura additiva include processi molto diversi tra loro, ma che presentano molti punti in comune come la flessibilità, libertà di progettazione e personalizzazione. Sfruttando queste proprietà è possibile realizzare oggetti su misura, soprattutto in campi come quello biomedicale dove la personalizzazione e la specificità sono fondamentali.The following thesis aims to study and to develop biomedical devices made through additive manufacturing. Additive manufacturing has been experiencing a strong growth in recent years, mainly due to its ability to easily realize complex geometries. This feature allows customization of products at a competitive cost. In addition, material waste is greatly reduced by the manufacturing principle. All these properties helped the recent years diffusion of additive manufacturing in fields such as automotive, aerospace and biomedical. This thesis focuses on the use of some of the most popular additive technologies for the production of biomedical devices. In particular, the work focused mainly on the fabrication of two models, the first to study the development of black floaters within the vitreous body of the eye, and the second to emulate the mandibular bone behavior during drilling for the installation of dental implants. The eye model consists of two main elements, a scaffold and a hydrogel. The scaffold contains and provides support to the hydrogel. It must be transparent, biocompatible easily handled in the laboratory. It is printed by stereolithography. The hydrogel, on the other hand, is intended to provide a 3D environment for cell growth and development. Therefore, it must be biocompatible and have adequate mechanical properties together with good printability. The 3D scaffold structure was made by material extrusion. The mandibular bone model was made by fused filament fabrication. The model consists of two parts, a solid outer part to emulate cortical bone, and a porous inner part to emulate trabecular bone. Drilling tests were performed with a dental drill attached to collaborative robots. Finally, the research covered two additional areas, the study of the properties of lattice structures made by laser-based- powder bed fusion and the evaluation of different surface finish treatments. The following thesis, therefore, has the following organization. Chapter 1 presents an introduction on additive manufacturing and bioprinting. The technologies and materials used are briefly described, and examples of additive manufacturing applications in the biomedical field are given. The following chapters, on the other hand, report published or forthcoming articles regarding the various topics mentioned above. Specifically, Chapter 2 reports the research on lattice structures and their fabrication. Chapters 3 and 4 include studies related to the eye model. Chapter 3 focuses on the fabrication of the support, and Chapter 4 on the formulation and evaluation of the hydrogel. Chapter 5 presents the study of the model for emulating the behavior of mandibular bone upon drilling, while Chapter 6, the last of this work, focuses on surface finishing processes. In conclusion, additive manufacturing includes various processes that are very different from each other but have many common points such as flexibility, freedom of design, and customization. By exploiting these properties, it is possible to make tailored objects, especially important in fields such as the biomedical one, where customization and specificity are a great added value.
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Sidney, Laura E. "Tissue engineering in hostile environments : the effects and control of inflammation in bone tissue engineering." Thesis, University of Nottingham, 2013. http://eprints.nottingham.ac.uk/13499/.
Full textAbstract:
The potential effects of introducing bone regeneration strategies into environments of disease and damage are often overlooked, despite the fact that many of the signalling pathways in inflammation have effects on bone development and healing. Embryonic stem cells (ESCs) are increasingly being used to develop models of disease and have potential in osteogenic-cell based therapies. Osteogenic differentiation strategies for ESCs are well established, but the response of these cells to tissue damage and inflammation has not yet been investigated, particularly in comparison to primary osteoblasts. Here, proinflammatory cytokines were used as part of an in vitro model to mimic elements of skeletal disease, such as rheumatoid arthritis and non-union fractures. The response of osteogenically differentiated mouse embryonic stem cells (osteo-mESCs) to the proinflammatory cytokines interleukin 1-β (IL-1β), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), was compared to that of primary mouse calvarial osteoblasts, already well-described in literature and used as a “benchmark” in this study. Although histology, immunocytochemistry and PCR showed similarities in osteogenic differentiation of the osteo-mESCs and the primary calvarial cells, over 21 days in culture, there were marked differences in the response to the proinflammatory cytokines. Viability of the osteo-mESCs was maintained in response to cytokines, whereas viability of primary cells was significantly reduced. There were marked increases in nitric oxide (NO) and prostaglandin E2 (PGE2) production in primary calvarial cells over the entire 21-day culture period, but this was not seen with osteo-mESCs until day 21. The study then went on to look at the effects of proinflammatory signalling on the in vitro bone formation of the two cell types. Significant differences in the effects of proinflammatory cytokines on bone nodule formation and matrix production were seen when comparing the osteo-mESCs and the calvarial cells. This study demonstrates that while osteo-mESCs share phenotypic characteristics with primary osteoblasts, there are some distinct differences in their biochemistry and response to cytokines. This is relevant to understanding differentiation of stem cells, developing in vitro models of disease, testing new drugs and developing cell therapies. An additional objective in this investigation was to look at tissue engineering strategies as a means of controlling inflammation in bone disease. The primary calvarial osteoblasts were utilised as an in vitro inflammation model, and used to study the effects of anti-inflammatory mediators. Anti-inflammatory-releasing porous scaffolds were manufactured from poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). The calvarial osteoblast inflammation model was used successfully to show successful release of diclofenac sodium from the PLGA/PEG scaffolds. This study demonstrates that there is much to consider in the development of regenerative strategies for bone disease, particularly the role that the effect and control of inflammation will play in bone healing.
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Ghezzi, Chiara Elia. "Dense collagen-based tubular tissue constructs for airway tissue engineering." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114489.
Full textAbstract:
To date, only engineered tissues of planar geometry, such as epidermal and dermal layer substitutes, have successfully reached the market, mainly due to their relative low complexity and simple geometry. In contrast, the mechanical and functional requirements of tubular tissues are more stringent compared to planar tissues. Tubular tissues, which are the main components of several biological systems (e.g. circulatory, urinary or respiratory), not only present an increased complexity in geometry and tissue architecture, they are also populated by mixed cell types. In addition, these are continuously exposed to cyclic mechanical stimuli, which modulate cellular responses and ultimately the functionality of the tissues. Therefore, the understanding and the ability to reproduce physiologically equivalent environments are critical to generate mechanically and biologically functional neo-tissues or tissue models. The aim of this doctoral research was to produce and characterize 3D DC-based tubular constructs as tissue models for airway tissue engineering in physiologically relevant culture conditions. The first objective was to develop DC-based constructs and evaluate, in real-time, the responses of seeded fibroblasts to PC and to culturing with the DC environment; the fabrication and characterization of mesenchymal stem cell (MSC) seeded multilayered DC-SF-DC hybrids; and to evaluate the differentiation of MSCs cultured within multilayered DC-SF-DC hybrids.The second objective was to develop and characterize cell-seeded tubular dense collagen constructs (TDCCs) with bioinspired mechanical properties.The third objective was to implement tubular dense collagen-based constructs as an airway tissue model through the evaluation of airway smooth muscle cell (ASMC) responses within TDCC under physiological mechanical stimuli, and the development of a multilayered tubular dense collagen-silk fibroin construct (TDC-SFC) that mimicked airway tract architecture in order to study MSC responses under physiological mechanical stimulation.By providing ASMCs with a physiologically equivalent niche, and through pulsatile flow stimulation, in vitro, ASMCs exhibited their native orientation, maintained their contractile phenotype and enhanced the mechanical properties of the TDCC through matrix remodelling. The ability of TDC-SFC to transfer physiological pulsatile stimulation to resident MSCs resulted in native-like cell orientation (i.e. parallel to circumferential strain), and induced MSC contractile phenotype expression.In conclusion, the tubular dense collagen-based constructs developed and implemented, in this doctoral dissertation, effectively provided an in vitro airway tissue model for potential preclinical studies to mimic physiological and pathological conditions (e.g. inflammatory and degenerative diseases) in a relevant biomechanical environment, as alternatives to simple tissue culture techniques or complex animal models.À ce jour, seuls les tissus synthétisés de forme plane, comme les substituts dermiques et épidermiques, ont réussi à percer le marché, surtout en raison de leur complexité relativement faible et de leur géométrie simple. À l'opposé, les exigences mécaniques et fonctionnelles des tissus tubulaires imposent un plus grand nombre de contraintes que les tissus planaires. Principales composantes de plusieurs systèmes biologiques (circulatoire, urinaire ou respiratoire), les tissus tubulaires sont non seulement plus complexes sur le plan de la géométrie et de l'architecture tissulaire, mais ils sont aussi composés de cellules de différents types. De plus, ils sont continuellement exposés à des stimuli mécaniques cycliques. Voilà pourquoi il est essentiel de comprendre les milieux physiologiquement équivalents et de pouvoir les reproduire si on veut obtenir des néotissus ou des modèles tissulaires fonctionnels sur le plan mécanique et biologique.La présente recherche de doctorat visait donc à produire et à caractériser des constructions tubulaires 3D à base de CD, les tissus des voies respiratoires dans des conditions de culture physiologiquement pertinentes. Le premier objectif était de concevoir des constructions à base de CD et d'évaluer la réaction des fibroblastes ensemencés à la CP et à la culture dans un milieu à base de CD; de fabriquer et de caractériser des hybrides multicouches CD-fibroïne-CD ensemencés de cellules souches mésenchymateuses (CSM); et d'évaluer la différenciation.Le deuxième objectif de la présente recherche était de concevoir et de caractériser des constructions tubulaires faites de collagène dense (CTCD). Le troisième objectif était d'implanter des constructions tubulaires à base de CD comme modèle tissulaire des voies respiratoires par l'évaluation de la réponse des cellules musculaires lisses (CML) des voies respiratoires dans les CTCD en présence de stimuli mécaniques physiologiques.En leur fournissant une niche physiologiquement équivalente, et grâce à la stimulation de l'écoulement pulsatoire, in vitro, les CML des voies respiratoires ont pris leur orientation naturelle, maintenu leur phénotype contractile et amélioré les propriétés mécaniques de la CTCD grâce au remodelage matriciel. La capacité de la CTCD à transférer la stimulation physiologique pulsatile aux CSM résidentes a donné une orientation des cellules s'apparentant à leur orientation naturelle et induit l'expression phénotypique.En conclusion, les constructions tubulaires à base de collagène dense qui ont été développées et implantées sont parvenues à fournir in vitro un modèle tissulaire des voies respiratoires pour d'éventuelles études précliniques visant à reproduire les conditions physiologiques et pathologiques.
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Chik, Tsz-kit, and 戚子傑. "Fabrication of multi-component tissue for intervertebral disc tissue engineering." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47849447.
Full textAbstract:
Intervertebral disc tissue engineering is challenging because it involves the
integration of multiple tissues with distinct structures and compositions such as
lamellar annulus fibrosus, gel?like nucleus pulposus and cartilage endplate. Each
of them has different compositions and different structures. It is hypothesized
that integration of tissues can be enhanced with appropriate mechanical and
biological stimuli. Meanwhile, effect of torsional stimulus on cell re?orientation
in mesenchymal stem cell?collagen tubular constructs is investigated in this study.
Furthermore, it is proposed that these findings can be used to fabricate a multicomponent
unit for intervertebral disc tissue engineering. It has been
demonstrated that mechanical and biological stimuli can stabilize the interface
between osteogenic and chondrogenic differentiated constructs with enhanced
ultimate tensile stress while the phenotype of osteogenic and chondrogenic
differentiated constructs were maintained. Scanning electronic microscopic
images have shown aligned collagen fibrils and presence of calcium at the
interface, indicating the possibility of the formation of a calcified zone. In
addition, it is proven that torsional stimulus triggered re?orientation of
mesenchymal stem cells in collagen lamellae towards a preferred angle. Cell
alignments were confirmed by using a MatLab?based program to analyze the
actin filament and the cell alignment via Phalloidin and Hematoxylin staining,
respectively. Cells and actin filaments were inclined around 30o from the vertical
axis, while cells and filaments in the control group (static loading) aligned along
the vertical axis. Furthermore, a double?layers bioengineered unit was fabricated,
with intact osteogenic differentiated parts at both ends. Comparatively higher
cell density was observed at the interface between layers, demonstrating the
interactions between layers, while the phenotype of each part was maintained in
14 days culture. This study concludes that a multi?components bioengineered
unit with preferred cell alignments can be fabricated. This provides new insights
to future development of bioengineered spinal motion segment for treating late
stage disc degeneration.published_or_final_version
Mechanical Engineering
Doctoral
Doctor of Philosophy
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Le, Thua Trung Hau. "Multimodality Treatment of Soft Tissue and Bone Defect: from Tissue Transfer to Tissue Engineering." Doctoral thesis, Universite Libre de Bruxelles, 2015. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/220961.
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In the first part of these studies, we have performed standard microsurgical procedures provide a solution for long standing bone and soft tissue defects, even in cases of longstanding osteomyelitis of long bones. When long bony segments are missing, the microvascular bone transfer provides a reliable method. In smaller soft tissue and bone defects, the application of a descending genicular osteomyocutaneous flap provides an option with low donor site morbidity. In the second part, we have focussed on reducing the donor site morbidity and expanded on the application of tissue engineering methods. MSCs derived from bone marrow can be injected percutaneous or be combined with an autologous bony scaffold for treatment of delayed union and nonunion. The outcome of our studies, however, limited in number of patients, clearly showed the possibilities and advantages of this new approach. A multimodality approach is essential, but it can provide promising solutions. Well-established microvascular and modern biotechnology methods will improve patient satisfaction and functional recovery in severe limb trauma, often the result of high-energy motorcycle accidents.Doctorat en Sciences médicales (Médecine)
info:eu-repo/semantics/nonPublished
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Ueda, Yuichiro. "Application of Tissue Engineering with Xenogenic Cells and Tissues for Regenerative Medicine." 京都大学 (Kyoto University), 2004. http://hdl.handle.net/2433/147657.
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Yang, Chao. "Tissue engineering of human cardiovascular patches." [S.l.] : [s.n.], 2005. http://www.diss.fu-berlin.de/2005/103/yang.pdf.
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Ndreu, Albana. "Electrospun Nanofibrous Scaffolds For Tissue Engineering." Master's thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/12608226/index.pdf.
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In this study a microbial polyester, poly(3-hydroxybutyrate-co-3-
hydroxyvalerate) (PHBV), and its blends were wet or electrospun into
fibrous scaffolds for tissue engineering.
Wet spun fiber diameters were in the low micrometer range (10-50 μ
m). The polymer concentration and the stirring rate affected the properties the most. The optimum concentration was determined as 15% (w/v). Electrospun fiber diameters, however, were thinner. Solution viscosity, potential, distance between the syringe tip and the collector, and polymer type affected the morphology and the thickness of beads formed on the fibers. Concentration was highly influential
as it increased from 5% to 15% (w/v) fiber diameter increased from 284 ±
133 nm to 2200 ±
716 nm. Increase in potential (from 20 to 50 kV) did not lead to the expected decrease in fiber diameter. The blends of PHBV8 with lactide-based v polymers (PLLA, P(L,DL-LA) and PLGA (50:50)) led to fibers with less beads and more uniform thickness. In vitro studies using human osteosarcoma cells (SaOs-2) revealed that wet spun fibers were unsuitable because the cells did not spread on them while all the electrospun scaffolds promoted cell growth and penetration. The surface porosities for PHBV10, PHBV15, PHBV-PLLA, PHBV-PLGA (50:50) and PHBV-P(L,DL)LA were 38.0±
3.8, 40.1±
8.5, 53.8±
4.2, 50.0±
4.2 and 30.8±
2.7%, respectively. Surface modification with oxygen plasma treatment slightly improved the cell proliferation rates. Consequently, all scaffolds prepared by electrospinning revealed a significant potential for use in bone tissue engineering applications
PHBV-PLLA blend appeared to yield the best results.
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Ziegelaar, Brian. "Tissue engineering of a tracheal substitute." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-18187.
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Junker, Johan. "Human Dermal Fibroblasts in Tissue Engineering." Doctoral thesis, Linköpings universitet, Cellbiologi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-19716.
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The loss or failure of tissues and/or organs is one of the most frequent problems in modern healthcare. The field of tissue engineering applies the principles of biology and engineering in order to develop functional substitutes for damaged tissues. Tissue engineering contains elements of medicine, material science and engineering with major components in focus being cells, biomaterials and soluble factors. All three components may be required for the development of clinical treatments. The usage of autologous tissue specific cells for clinical treatment is often not feasible due to poor growth kinetics or unstable phenotypes of the cells. Furthermore, lack of availability of healthy tissue that can be biopsied is a major problem in many applications. One approach to overcome this problem is to use adult stem cells which have the capacity to give rise to several different cell types. Although promising, adult stem cells have major impediments for use in several tissue engineering applications. The difficulties associated with harvest, culture and storage render problems in the development of clinically relevant procedures. During the last years, the inherent plasticity of differentiated somatic cells has been demonstrated. One of the easiest human cell types to obtain, expand and store is the dermal fibroblast. Recent reports indicate that dermal fibroblasts can be induced to differentiate towards several distinct mesenchymal lineages in vitro. The main aim of this thesis was to investigate the inherent stem cell plasticity of human dermal fibroblasts and explore their possible usefulness in tissue engineering applications. The papers included in this thesis employ routine and immunohistochemical staining, enzyme activity assay, analysis of low density lipoprotein incorporation, capillary-like network formation assay and full expression micro array analysis. Fibroblasts were shown to differentiate towards adipocyte, chondrocyte, endothelial and osteoblast-like cell types in vitro. The differentiation from fibroblasts to myofibroblasts in burn scar tissue upon stimulation by mechanical tension was also demonstrated. Adipogenic, chondrogenic and osteogenic induced fibroblasts display the upregulation of several genes associated with adipocytes, chondrocytes and osteoblasts.
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Tse, Christopher Chi Wai. "Utilising inkjet printing for tissue engineering." Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/13950/.
Full textAbstract:
The field of tissue engineering has the potential to improve the quality of life of individuals through combining the knowledge of engineering and life sciences in creating engineered biological substitutes that repair, support and enhance tissue function. Inkjet printing is a versatile tool that can be used for a broad range of applications. Ubiquitous in households, offices and industry, there has been growing interest in the use of inkjet printing for biological applications. Inkjet printing allows the user to deposit nano-picolitre volume of inks of low viscosity with high precision and high repeatability. Within this thesis, inkjet printing was used to explore its applications in the life sciences, with jetting behaviour and scaffold design optimised. The creation of cell-friendly scaffolds was investigated. Gelatin scaffolds, crosslinked with inkjet printed glutaraldehyde were fabricated. Fibroblasts were seeded onto these fabricated scaffolds and shown to proliferate without hindrance, allowing a method to create sub-millimetre cell-friendly fibres for tissue engineering applications. The ability for inkjet printing to create scaffolds to control cell alignment was investigated. Cell orientation can be controlled through inkjet printing paraffin wax to restrict cell proliferation on a substrate. Paraffin wax is not harmful or toxic to cells, and cells were able to grow within the negative spaces between the wax patterns, to create aligned cell culture as cells proliferated. An advantage with the wax scaffolds was that the wax scaffold was readily removable with a scalpel that allowed further analysis of cell behaviour when proliferating into an unrestricted space. A proportion of cells was also detached upon wax removal, proportional to cell density within the wax scaffold and wax channel width. After wax removal, cell cultures quickly lost their ordered appearance within 3 days as they proliferated randomly across the substrate. The creation of in vitro vasculature models through the use of a combination of inkjet-printed wax, PDMS moulding and wax-loss method to create medical phantoms for the study of rheological behaviour was studied. The scalloping behaviour of the printed wax vessel was reduced in the final phantom created, as there would be a thin lining of wax that covers the interior of the PDMS mould after wax removal, making the vessel smoother. Cell printing of neuronally relevant cells were investigated. NG108-15 and porcine Schwann cells (along with fibroblasts to act as a control experiment) were inkjet printed, studying cell viability during and after inkjet printing. It was concluded that cells were not significantly damaged during inkjet printing over a wide range of voltages (50 V-230 V), and no correlation was seen to show an increase in cell death with increasing voltages. Inkjet printed NG108-15 cells showed they produced longer neurites compared to control samples after 7 days. Further to results, it was confirmed that cell printing is limited to a duration of less than 40 minutes due to cell aggregation within the reservoir of the printing system, causing a steady significant decrease in cell numbers during printing.
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Holy, Chantal E. "Bone tissue engineering on biodegradable polymers." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape8/PQDD_0012/NQ59097.pdf.
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Sachlos, Eleftheherios. "Tissue engineering with solid freeform fabrication." Thesis, University of Oxford, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418645.
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Qiao, Xiangchen. "Scaffold fabrication for bone tissue engineering." Thesis, University of Leeds, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.550345.
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An ideal engineered scaffold should support the regeneration of natural extracellular matrix; for bone this is principally Type I collagen and hydroxyapatite. The present work investigated the fabrication and characterisation of scaffolds comprised of (a) PCL or (b) Type I collagen +/- PDLLA produced via electrospinning and studied their influence on osteogenic regeneration. A parallel study examined the cellular response of human bone marrow stromal cells to nano-crystalline hydroxyapatite particles in a foamed PDLLA scaffold. Both the influence of particle size and chemical substitution were considered. Characterisation of materials involved scanning electron microscopy, Fourier transform infrared spectroscopy, circular dichroism, atomic force microscopy and histology. Electrospun PCL nanofibrous scaffolds potentially supported osteogenic regeneration. However, the scaffolds had to be treated post- spinning with NaOH and fetal calf serum to make them more hydrophilic to support cell attachment. With a view to producing a biomimetic material and knowing that hydrophobicity is not an issue for Type I collagen, rat-tail derived Type I collagen was selected for further studies. A number of solvents were explored to successfully electrospin the collagen. Although the wet stability of resultant scaffolds was poor, crosslinking improved scaffold stability, particularly the use of glutaraldehyde vapour. The observed denaturation. of collagen was determined to be a consequence of conformational changes rather than scission of collagen polypeptides, indicating that the electrospun collagen was not a simple analogous to gelatin. An alternative approach to stabilisation involved electrospinning collagen with a co-polymer, PDLLA, which successfully stabilised the fibrous scaffolds in the ratio ranges of 40- 60 wt% PDDLA: 60-40 wt% collagen. Future work will combine these materials with the optimised apatite filler to produce a composite material since the parallel study on cell culture of minerallPDLLA composites suggested that incorporation of mineral components did indeed enhance the alkaline phosphatase activity of human bone marrow stromal cells. Strontium substituted hydroxyapatite introduced potential benefits on alkaline phosphatase activity of bone derived cells in basal media.
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Blackwood, Keith Alan. "Electrospun scaffolds for soft tissue engineering." Thesis, University of Sheffield, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.548559.
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Arumugam, M. Q. "Porous scaffolds for bone tissue engineering." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596173.
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The aim of this thesis is to investigate the behaviour of cells in porous scaffolds. Three types of porous scaffold were investigated; porous phase-pure hydroxyapatite, porous silicon-substituted hydroxyapatite and a novel mineralised (brushite) collagen-glycosaminoglycan (GAG) scaffold. Methods were derived to optimise the seeding of cells within these scaffolds and the differentiation of bone and marrow-derived cells in short-term culture was investigated using molecular biology and ELISA techniques. Novel techniques were developed to assess the response of cells within the centre of the scaffolds. The effect of soluble silicon on bone-derived cells was also investigated to consider reasons for the enhanced cell differentiation seen with porous silicon-substituted hydroxyapatite scaffolds as compared with porous phase-pure hydroxyapatite. All three scaffold types were able to maintain bone and marrow-derived cells in short term culture up to 21 days. However, the composite mineralised collagen-GAG was found to sustain the greatest number of cells and appeared to promote greater differentiation of cells in the 7-21 day period. A 6-week in vivo sheep bone model was performed to assess the clinical viability of the mineralised collagen-GAG as a bone substitute material. Three types of calcium phosphate/collagen/GAG composite, namely hydroxyapatite, brushite and octacalcium phosphate were compared to unmineralised collagen-GAG and autograft controls. Subsequent analysis of bone formation revealed that, while there was no statistical difference between the three mineral-incorporating composites, they all produced more new bone within porous scaffolds than unmineralised collagen-GAG, but, as expected, less than for the autograft control. It is concluded that the calcium-phosphate collagen-GAG composite offers the clinical prospect of hard-soft tissue replacement mimicking the bone-cartilage interface.
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Teichmann, Juliane. "Tissue Engineering des Humanen Cornealen Endothels." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-131578.
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Das corneale Endothel bildet die innere, einschichtige Zelllage der Cornea und ist für die Aufrechterhaltung der cornealen Transparenz zuständig. Krankheiten oder Verletzungen des cornealen Endothels können zu schweren Beeinträchtigungen des Sehvermögens führen und eine corneale Transplantation erforderlich machen. Der während und nach der Operation auftretende endotheliale Zellverlust erschwert das Überleben des Transplantates. Darum besteht ein Hauptziel des cornealen Tissue Engineerings in der Bereitstellung von transplantierbaren humanen cornealen Endothelzellsheets (HCEC-Sheets) mit einer adäquaten Zelldichte.
Thermo-responsive Zellkulturträger fanden für die schonende, enzymfreie Gewinnung von Zellsheets für verschiedene Gewebetypen bereits Verwendung. HCEC stellen in diesem Kontext einen besonderen Fall dar, da sie eine starke Adhäsion zu ihrem Kultursubstrat ausbilden, was deren schonende, thermisch induzierte Ablösung als funktionelles Zellsheet erschwert. Im Rahmen dieser Arbeit wurde ein neuartiger thermo-responsiver Zellkulturträger entwickelt. Dieser basiert auf dem durch Elektronenbestrahlung immobilisierten und vernetzten thermo-responsiven Polymer Poly(vinylmethylether) (PVME) sowie dem alternierenden Co-Polymer Poly(vinylmethylehter-alt-maleinsäureanhydrid) (PVMEMA) als biofunktionalisierbare Komponente. Die Kombination dieser Polymere führte zur Etablierung eines thermo-responsiven Zellkulturträgers, dessen physikochemische und biomolekulare Eigenschaften in weiten Grenzen einstellbar und dadurch an die spezifischen Anforderungen von HCEC anpassbar waren.
Das PVME-PVMEMA-Blend ermöglichte die Bildung konfluenter HCEC-Monolayer mit den morphologischen Grundlagen für ein funktionelles corneales Endothelgewebe. Durch Inkorporation von Poly(N-isopropylacrylamid) (PNiPAAm) als weitere thermo-responsive Polymerkomponente konnte das Ablösungsverhalten funktioneller HCEC-Sheets weiter verbessert werden. In einem weiteren Schritt erfolgte der Transfer abgelöster HCEC-Sheets auf ein planares, biofunktionalisiertes Kultursubstrat sowie auf endothelfreie porcine Corneae. Die HCEC-Sheets wurden auch nach dem Transfer umfassend biologisch analysiert. Diese Arbeit legt einen Grundstein für die Bereitstellung klinisch anwendbarer Alternativen für das Tissue Engineering von cornealem Gewebe.
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Herrmann, P. "Tissue engineering of upper airway replacements." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1533028/.
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Laryngotracheal diseases cause considerable morbidity and fully functional replacement after extensive surgical resection is still missing. Regenerative medicine has made considerable progress towards clinical transplantation and offers a potentially attractive solution. To date the use of biological scaffolds is considered promising for tissue engineering, providing structural and microbiological support for cell seeding and integration in the host environment. This thesis investigates the possibility of developing a decellularization protocol suitable for the production of upper airway constructs for clinical transplantation. In the first part of this work a new decellularization protocol for tracheal tissue and laryngeal tissue of different species was developed. The novel use of vacuum technology was explored. Resultant biological scaffolds were characterised by assessment of immunogenicity (H&E staining, DNA quantification, immunohistochemistry and biocompatibility) and extra-cellular matrix architecture (histology, quantitative protein assays, SEM) and biomechanical properties. In the following part of this work the resultant porcine laryngeal scaffolds seeded with human epithelial and mesenchymal stem cells were tested in a large animal model in comparison to a synthetic scaffold. Study duration was two months. In vivo assessments included regular endoscopies with cytological brushings, CT scans and blood tests. Post-mortem analysis included histology and immunohistochemistry. The data supported the hypothesis that biological, decellularized scaffolds possess some advantages for laryngeal bioengineering compared to the synthetic scaffold tested in this thesis.
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Kocaba, Viridiana. "Tissue engineering pour la reconstruction cornéenne." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1078.
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En France, les dysfonctions endothéliales représentent environ la moitié des indications de greffes de cornée réalisées chaque année. Cependant, les problématiques liées à la pénurie de greffon, aux difficultés des techniques chirurgicales de greffes endothéliales ainsi qu’aux risques d’échec ou de rejet de greffe poussent les chercheurs à développer de nouvelles thérapies moins invasives et plus efficaces. La thérapie cellulaire cornéenne endothéliale est une des voies de recherche actuellement explorées dont le but est de s’affranchir des aléas de la greffe de cornée. La cornée humaine est un tissu idéal pour la thérapie cellulaire. Grâce à ses caractéristiques d’organe à la fois avasculaire et immunitairement privilégié, les cellules transplantées sont ainsi bien mieux tolérées par rapport aux autres tissus et organes vascularisés. Les avancées dans le domaine des cellules souches, de l'ingénierie, particulièrement avec l’arrivée des greffes de cellules souches épithéliales pour le traitement des pathologies sévères de la surface oculaire, ont suscité un intérêt massif afin d’adapter ces techniques aux cellules endothélialesIn France, around half of all corneal keratoplasties are performed to treat corneal endothelial dysfunction each year. However, the use of endothelial keratoplasty is limited by the technical difficulty of the procedure, a shortage of available grafts, and the potential for graft failure or rejection. These limitations are driving researchers to develop new, less invasive, and more effective therapies. Corneal endothelial cell therapy is being explored as a potential therapeutic measure, to avoid the uncertainty associated with grafting. The human cornea is an ideal tissue for cell therapy as owing to its avascular characteristics, transplanted cells are better tolerated compared with other vascularized tissues and organs. Advances in the field of stem-cell engineering, particularly the development of corneal epithelial stem cell therapy for the treatment of severe diseases of the ocular surface, have aroused a massive interest in adapting cell-therapy techniques to corneal endothelial cells
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Radisic, Milica. "Biomimetic approach to cardiac tissue engineering." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/28665.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2004."September 2004."
Includes bibliographical references.
(cont.) biochemical and morphological properties in the pretreated group. Finally, in order to mimic capillary structure cardiac fibroblasts and myocytes were co-cultured on a scaffold with a parallel channel array that was perfused with culture medium supplemented with synthetic oxygen carrier (PFC emulsion). Presence of the PFC emulsion resulted in significantly higher cell density and improved contractile properties compared to the constructs cultivated in the culture medium alone, by increasing total oxygen content and effective diffusivity.
Heart disease is the leading cause of death in the Western world. Tissue engineering may offer alternative treatment options or suitable models for studies of normal and pathological cardiac tissue function in vitro. Current tissue engineering approaches have been limited by diffusional oxygen supply, lack of physical stimuli and absence of multiple cell types characteristic of the native myocardium. We hypothesized that functional, clinically sized (1-5 mm thick), compact cardiac constructs with physiologic cell densities can be engineered in vitro by mimicking cell microenvironment present in the native myocardium in vivo. Since cardiac myocytes have limited ability to proliferate we developed methods of seeding cells at high densities while maintaining cell viability. Cultivation of cardiac constructs in the presence of convective-diffusive oxygen transport in perfusion bioreactors, maintained aerobic cell metabolism, viability and uniform distribution of cells expressing cardiac markers. To improve cell morphology and tissue assembly cardiac constructs were cultivated with electrical stimulation of contraction in a physiologically relevant regime. Electrical stimulation enabled formation of tissue with elongated cells aligned in parallel and with organized ultrastructure remarkably similar to the one present in the native heart. To investigate the effect of multiple cell types on the properties of engineered cardiac tissue cardiac fibroblasts and cardiac myocytes were cultivated synchronously, separately or serially (pretreatment of scaffolds with fibroblasts followed by the addition of myocytes). Presence of fibroblasts remarkably improved contractile response of the engineered cardiac constructs with the superior
by Milica Radisic.
Ph.D.
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Ling, Yibo. "Hydrogel cell encapsulation for tissue engineering." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/44456.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2008.Vita.
Includes bibliographical references (leaves 116-123).
The engineering of artificial tissues for restoration or replacement of organ function holds the potential to alter the landscape of medical therapeutics. In many tissue engineering approaches, cells seeded within 3D porous structures are expected to remodel into tissue-like structures. Despite significant progress, difficulties in lack of control over tissue architecture as well as vascularization continue to limit the efficacy of engineered constructs. This thesis describes work aimed at tackling these two problems. First, two techniques for generating size- and shape-controlled cell-laden hydrogels are described in the context of potential modular assembly for conferring greater control over the geometry of homotypic and heterotypic cell arrangements within engineered tissues. Then, a method for producing cell-loaded microfluidic agarose hydrogels for tissue engineering is described.
by Yibo Ling.
S.M.
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Carrier, Rebecca Lyn 1973. "Cardiac tissue engineering : bioreactor cultivation parameters." Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/8999.
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Thesis (Sc.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2000.Includes bibliographical references.
Tissue engineering may be useful in fighting heart disease since it offers the possibility of creating functional tissue equivalents for scientific studies and tissue repair. In the present work, we examined how variations in cultivation parameters of a model tissue engineering system influenced cardiac tissue morphogenesis. The central hypothesis was that using a tissue engineering system consisting of isolated cardiac cells, polymer scaffolds, and tissue culture bioreactors, we could engineer cardiac muscle mimicking native tissue in structure and function in the presence of appropriate biochemical and physical signals. The specific objectives were to: ( 1) vary key parameters of the model tissue engineering system, and (2) structurally and functionally characterize engineered cardiac muscle so that effects of parameter variations could be assessed and engineered tissue could be compared to native tissue. Effects of key cultivation parameters, including (I) cell source, (2) cell seeding density, (3) cell seeding vessel, and (4) tissue culture bioreactor on structure and function of engineered cardiac cell-polymer constructs were studied. Advantages of seeding mammalian cells at high densities (6-Sx 106 cells/Smm diameter x 2mm thick scaffold) under mixed conditions and culturing constructs in rotating laminar flow bioreactors were demonstrated, but constructs had interiors (> IOOμm tissue depth) consisting of mostly empty space due to diffusional mass transport limitations. We attempted to overcome diffusional limitations by directly perfusing culture medium through the constructs. Perfusion significantly improved the uniformity of the cell distribution and enhanced expression of a differentiated cell phenotype in comparison to non-perfused (i.e. flask) cultures. Control of the cell microenvironment in the perfusion system was also used to study relationships between oxygen tension and properties of cardiac constructs. Oxygen tension was directly correlated with DNA and protein contents (r=0.88 and 0.89, respectively), aerobic metabolism (r=0.97), muscle protein expression, and ultrastructural differentiation. Characterization of cardiac construct structure, composition, cell phenotype, and in vitro function demonstrated cardiac specific protein expression, metabolic activity similar to that of native tissue, and differentiated ultrastructural features (e.g. sarcomeres). The results support the utility of engineered cardiac muscle as a native tissue model for in vitro studies and eventually for in vivo tissue repair.
by Rebecca Lyn Carrier.
Sc.D.
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Li, Siwei. "Cartilage tissue engineering : a multidisciplinary approach." Thesis, University of Southampton, 2013. https://eprints.soton.ac.uk/407512/.
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Degeneration of articular cartilage and associated osteoarthritic changes are the leading cause of compromised joint articulation worldwide. Early stages of osteoarthritis (OA) are characterised by partial thickness chondral defects that fail to heal spontaneously. It is crucial to repair these defects during the early stages of cartilage degeneration to prevent the progression of OA. Currently used clinical interventions however have been unable to completely restore/regenerate damaged articular cartilage to its native state. This has led to considerable interest in the development of effective cartilage tissue engineering strategies for the treatment of chondral defects in an increasing ageing population. The present study aims to address some of the hurdles in cartilage regeneration, in particular, (i) identification of an appropriate cell source, (ii) an understanding the effect of oxygen on cartilaginous matrix formation, and (iii) the application of a novel bioreactor design for the generation of neocartilage grafts. Human articular chondrocytes (HACs) demonstrated excellent cartilage formation in both scaffold-free pellet culture and culture using three-dimensional biomaterial scaffolds. Chondrogenic differentiation of STRO-1-immunoselected skeletal stem cells (STRO-1+ SSCs) was significantly improved by the utilisation of scaffolds with a highly interconnected porous architecture in comparison to scaffold-free pellet culture. The predeposition of SSCs for hypertrophic differentiation however indicated a need for further development of cell culture protocols that may otherwise limit their application in cartilage bioengineering strategies. A combined experimental-computational approach was utilised to infer the likely effects of oxygen tension on cartilaginous matrix synthesis by HACs in the 3-D pellet culture model, from which a threshold oxygen tension (pO2 ≈ 8% atmospheric pressure) that separated collagenous matrix formation from PG deposition was determined. This study has also demonstrated the first successful application of perfusion bioreactor technology in combination with ultrasound cell trapping for the generation of “scaffold-free” neocartilage grafts of HACs that were analogous to native hyaline cartilage. Furthermore, the neocartilage grafts were able to adhere to host articular cartilage and mediate repair of partial thickness chondral defects. The work presented in this thesis has demonstrated the successful application of a multidisciplinary approach, encompassing skeletal cell biology, bioengineering, mathematical modelling and acoustofluidics, for the generation of neocartilage grafts ex vivo that could be ultimately scaled-up and subsequently used in the clinic for resurfacingarticular cartilage defects.
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Hurley, Jennifer R. "Tissue engineering strategies for cardiac regeneration." University of Cincinnati / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1320681698.
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Haji, Ruslan Khairunnisa Nabilah. "Protein hydrogels as tissue engineering scaffolds." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/protein-hydrogels-as-tissue-engineering-scaffolds(45ff4e72-49ea-46df-9e7b-b9113576c096).html.
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Hydrogels aim to mimic the natural living environment by entrapping large amount of water or biological fluids in their polymeric network. There has been growing interest in the development of peptide and protein hydrogels, due to their improved biocompatibility, biodegradability and biological properties in comparison to purely synthetic polymer hydrogels. Under the appropriate conditions, biomacromolecular protein hydrogels can self-assemble into ordered meso- to macroscopic supramolecules with better resulting networks that promote tissue development. The work presented here mainly focuses on producing protein hydrogels with controlled physical properties useful for tissue regeneration process and drug delivery applications. Hen egg white lysozyme (HEWL) hydrogels were studied in the presence of water and different reducing agents forming three HEWL systems including HEWL/water, HEWL/DTT and HEWL/TCEP gels. Strong, self-supporting HEWL gels were successfully prepared in the range of pH 2 to 7, using a temperature of 85°C. At pH 2, the protein denaturation in water was relatively slow resulting in a high percentage of turn structure (~50%) that promotes HEWL gelation after 3 days of heating. No lysozyme gelation in water was observed at pH 3, 4 and 7 even after 21 days of heating. A small quantity of DTT (~20 mM) was added to encourage lysozyme unfolding and HEWL/DTT samples formed gels at higher pH including at physiological pH. The pH 2 HEWL/water gel was found to be stronger but more brittle than pH 7 HEWL/DTT gel. It was observed there were some irregularities in the distribution of pH 2 fibrils (~7µm in length) that form large pore sizes within the network. The pH 7 sample contained shorter and stiff fibrils with repetitive polygon-shaped mesh network. The use of TCEP, which is a stronger reductant than DTT, led to the formation of self-supporting HEWL gels between pH 3.5 and 5.5. The highest storage modulus was observed at pH 5, which is related to the high β-sheet content of the sample (~45%). In addition, a promising strategy has been devised to form thermoresponsive HEWL hydrogels by synthesising and incorporating a small fraction of lysozyme-PNIPAAm bioconjugates into the major protein matrix. Results show the thermoresponsive nature of PNIPAAm was conferred to HEWL protein that exhibits higher storage stability in response to changing temperature.
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Dreesmann, Lars. "Zelluläre Mechanismen beim Neuro Tissue-Engineering." [S.l. : s.n.], 2007. http://nbn-resolving.de/urn:nbn:de:bsz:100-opus-2100.
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Junker, Johan P. E. "Human dermal fibroblasts in tissue engineering /." Linköping : Department of Clinical and Experimental Medicine, Linköping University, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-19716.
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McDevitt, Todd C. "Spatially controlled engineering of myocardial tissue /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/8090.
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