Background: In addition to conventional chemotherapeutics, nucleic acid-based therapeutics like antisense oligodeoxynucleotides (AS-ODN) represent a novel approach for the treatment of bladder cancer (BCa). An efcient delivery of AS-ODN to the urothelium and then into cancer cells might be achieved by the local application of multiwalled carbon nanotubes (MWCNT). In the present study, pristine MWCNT and MWCNT functionalized with hydrophilic moieties were synthesized and then investigated regarding their physicochemical characteristics, dispersibility, biocompatibility, cellular uptake and mucoadhesive properties. Finally, their binding capacity for AS-ODN via hybridization to carrier strand oligodeoxynucleotides (CS-ODN), which were either non-covalently adsorbed or covalently bound to the diferent MWCNT types, was evaluated. Results: Pristine MWCNT were successfully functionalized with hydrophilic moieties (MWCNT-OH, -COOH, -NH2, -SH), which led to an improved dispersibility and an enhanced dispersion stability. A viability assay revealed that MWCNTOH, MWCNT-NH2 and MWCNT-SH were most biocompatible. All MWCNT were internalized by BCa cells, whereupon the highest uptake was observed for MWCNT-OH with 40% of the cells showing an engulfment. Furthermore, all types of MWCNT could adhere to the urothelium of explanted mouse bladders, but the amount of the covered urothelial area was with 2–7% rather low. As indicated by fuorescence measurements, it was possible to attach CS-ODN by adsorption and covalent binding to functionalized MWCNT. Adsorption of CS-ODN to pristine MWCNT, MWCNT-COOH and MWCNT-NH2 as well as covalent coupling to MWCNT-NH2 and MWCNT-SH resulted in the best binding capacity and stability. Subsequently, therapeutic AS-ODN could be hybridized to and reversibly released from the CS-ODN coupled via both strategies to the functionalized MWCNT. The release of AS-ODN at experimental conditions (80 °C, bufer) was most efective from CS-ODN adsorbed to MWCNT-OH and MWCNT-NH2 as well as from CS-ODN covalently attached to MWCNT-COOH, MWCNT-NH2 and MWCNT-SH. Furthermore, we could exemplarily demonstrate that AS-ODN could be released following hybridization to CS-ODN adsorbed to MWCNT-OH at physiological settings (37 °C, urine). Conclusions: In conclusion, functionalized MWCNT might be used as nanotransporters in antisense therapy for the local treatment of BCa.

Background: In addition to conventional chemotherapeutics, nucleic acid-based therapeutics like antisense oligodeoxynucleotides (AS-ODN) represent a novel approach for the treatment of bladder cancer (BCa). An efcient delivery of AS-ODN to the urothelium and then into cancer cells might be achieved by the local application of multiwalled carbon nanotubes (MWCNT). In the present study, pristine MWCNT and MWCNT functionalized with hydrophilic moieties were synthesized and then investigated regarding their physicochemical characteristics, dispersibility, biocompatibility, cellular uptake and mucoadhesive properties. Finally, their binding capacity for AS-ODN via hybridization to carrier strand oligodeoxynucleotides (CS-ODN), which were either non-covalently adsorbed or covalently bound to the diferent MWCNT types, was evaluated. Results: Pristine MWCNT were successfully functionalized with hydrophilic moieties (MWCNT-OH, -COOH, -NH2, -SH), which led to an improved dispersibility and an enhanced dispersion stability. A viability assay revealed that MWCNTOH, MWCNT-NH2 and MWCNT-SH were most biocompatible. All MWCNT were internalized by BCa cells, whereupon the highest uptake was observed for MWCNT-OH with 40% of the cells showing an engulfment. Furthermore, all types of MWCNT could adhere to the urothelium of explanted mouse bladders, but the amount of the covered urothelial area was with 2–7% rather low. As indicated by fuorescence measurements, it was possible to attach CS-ODN by adsorption and covalent binding to functionalized MWCNT. Adsorption of CS-ODN to pristine MWCNT, MWCNT-COOH and MWCNT-NH2 as well as covalent coupling to MWCNT-NH2 and MWCNT-SH resulted in the best binding capacity and stability. Subsequently, therapeutic AS-ODN could be hybridized to and reversibly released from the CS-ODN coupled via both strategies to the functionalized MWCNT. The release of AS-ODN at experimental conditions (80 °C, bufer) was most efective from CS-ODN adsorbed to MWCNT-OH and MWCNT-NH2 as well as from CS-ODN covalently attached to MWCNT-COOH, MWCNT-NH2 and MWCNT-SH. Furthermore, we could exemplarily demonstrate that AS-ODN could be released following hybridization to CS-ODN adsorbed to MWCNT-OH at physiological settings (37 °C, urine). Conclusions: In conclusion, functionalized MWCNT might be used as nanotransporters in antisense therapy for the local treatment of BCa.

With the growing demands for bone implant therapy, titanium (Ti) and its alloys are considered as appropriate choices for the load-bearing bone implant substitutes. However, the interaction of bare Ti-based implants with the tissues is critical to the success of the implants for long-term stability. Thus, surface modifications of Ti implants with biocompatible hydroxyapatite (HAp) coatings before implantation is important and gained interest. Sol-gel is a potential technique for deposition the biocompatible HAp and has many advantages over other methods. Therefore, this review strives to provide widespread overview on the recent development of sol-gel HAp deposition on Ti. This study shows that sol-gel technique was able to produce uniform and homogenous HAp coatings and identified the role of surface pretreatment of Ti substrate, optimizing the sol-gel parameters, substitution, and reinforcement of HAp on improving the coating properties. Critical factors that influence on the characteristics of the deposited sol-gel HAp films as corrosion resistance, adhesion to substrate, bioactivity, morphological, and structural properties are discussed. The review also highlights the critical issues, the most significant challenges, and the areas requiring further research.

The present work deals with the comparison of the properties of metallic biomaterials in terms of their suitability for use as a temporary metal implant. In the work is judged biocompatibility of materials, they are comparing the corrosion rates and the influence of additives in the iron alloy to change biocompatibility and corrosion rate. In a part of this work is suggesting a method of preparing biodegradable metallic samples with different alloying elements and determine the methods, processes and measuring the corrosion rates. Part of this work is the chapter dealing with the function and effect of iron in the human body and any complications that may occur when a surplus caused by the release of part of the implant during its degradation or corrosion products. The outcome of this work is sort of created an iron-based samples in terms of their electrochemical corrosion potential, corrosion rate of samples exposed in various corrosive solutions, spectroscopic elemental analysis and outputs from the microscopic observation of the structures.

This thesis refers to Fe-based biodegradable materials and their potencial aplications in medicine, especially as temporary bone implants. This work generaly summaries aplications of biomaterial in medicine with more interest kept on biodegradable materials and their in-vivo corrosion. The experimental part refers to conduction of porous Fe-based materials with silica addition. The structure of prepared specimens is identified by EDX and XRD analysis. The imersion test and electrochemical studies were conducted to observe corrosion behaviour with respect to different concentration of silica. Potenciodynamic curves were obtained to determine corrosion potencial and corrosion current density of prepared samples.

Ce travail a consisté à optimiser la synthèse de phosphates de calcium (CaP) déposés sur tissus de fibres de carbone (TFC) par procédé de sono-électrodéposition afin d’obtenir des revêtements uniformes. Les paramètres électrochimiques clés optimisés sont le type et la durée de polarisation cathodique ainsi que la température de l’électrolyte. Pour un potentiel constant de -1 V à 70 °C, un régime d’électrolyse contrôlé de l’eau conduit à la formation d’un revêtement plaquettaire d’hydroxyapatite déficitaire en calcium (CDA) carbonatée. Les plaquettes sont composées de particules lamellaires (de quelques dizaines à centaines de nm) constituées de CDA carbonatée de structure ordonnée au coeur et de structure désordonnée car hydratée en surface des particules, organisation typique des apatites biomimétiques. Le matériau hybride a été dopé en strontium, engendrant la formation de revêtements où les ions Ca²+ sont substitués par des ions Sr²+ de manière contrôlée, conférant au biomatériau de nouvelles propriétés en vue d’une application en régénération osseuse. Ce travail a aussi démontré la possibilité d’adsorber de façon sélective des principes actifs ciblés (tétracycline, naproxène, aspirine) dans chaque constituant du matériau hybride. Les courbes de désorption ont mis en évidence deux modes de libération selon le principe actif.Une évaluation biologique des différentes matériaux hybrides a été réalisée. L’étude in vitro a porté sur la viabilité et la prolifération d’ostéoblastes humains en surface des biomatériaux hybrides, démontrant leur biocompatibilité. L’intérêt d’un dopage (Sr²+, aspirine et naproxène) sur l’activité des ostéoblastes a été démontré. Une expérience pilote in vivo a été menée, consistant à créer un défaut osseux dans des fémurs de rats et à étudier l’influence du type de biomatériaux TFC/CaP sur les évolutions quantitative et qualitative de la régénération osseuse. / Optimization of the synthesis of calcium phosphates (CaP) on carbon fiber cloths (TFC) was performed in using sono-electrodeposition process in order to obtain uniform coatings. The electrochemical potential applied and the electrolyte temperature during the synthesis were determined as being key parameters. For a constant potential of -1 V at 70 ° C, a controlled water electrolysis regime results in the deposit of plate-like calcium-deficient apatite (CDA). This plate-like particles (from a few tens to hundreds of nm in length) consist in an ordered structure of carbonated CDA in their core and in a disordered structure in the hydrated surface, a typical organization of biomimetic apatites. The hybrid material was doped with strontium, resulting in a carbonated CDA coating where the Ca²+ ions are controllably substituted by Sr²+ ions, leading to new properties for a bone regeneration application. This work has also shown the possibility of selectively adsorb targeted active molecules (tetracycline, naproxen, aspirin) in each component of the hybrid material. The desorption curves revealed two modes of release depending on the active molecule.A biological evaluation of the different hybrid materials was carried out. The in vitro study investigated the viability and proliferation of human osteoblasts at the surface of hybrid materials, demonstrating their biocompatibility. The interest of a doping (Sr²+, aspirin and naproxen) on osteoblast activity was demonstrated. An in vivo pilot experiment was conducted, through the creation of a bone defect in rat thighbones to study the influence of TFC/CaP biomaterials on the quantitative and qualitative evolutions of bone regeneration.

L’architecture des biomatériaux de comblement osseux à un réel impact sur l’activité cellulaire, la vascularisation et la diffusion de facteurs de croissance. Dans un premier temps, différentes membranes de polystyrène (PS) composées de fibres alignées ou aléatoires ont été étudiées. Elles sont non biodégradables et pourraient servir de supports pour la régénération de larges défauts osseux. Nous avons montré la cytocompatibilité in vitro des membranes en analysant l’adhésion, la prolifération et la différenciation cellulaire. Ensuite, des membranes de PS ont été enrichies de grains de β-TCP ou de nanoparticules d’or. Nous les avons implantées dans un modèle de défaut crânien de taille critique chez la souris. L’addition de β-TCP a stimulé la repousse osseuse grâce à la grande bioactivité des céramiques. Les membranes ont été biotolérées, les fibres ont été encapsulées dans l’os néoformé mais également dans un tissu conjonctif dense. Les nanoparticules d’or immobilisées sur des fibres ont migré dans l’os ou ont été phagocytées. Dans un second temps, différentes formulations de granules poreux de β-TCP ont été analysées par nanotomographie aux rayons X. L’architecture macroporeuse des granules varie inversement avec la concentration en β-TCP. Les faces internes montrent une grande hétérogénéité de minéralisation. Pour mimer les conditions d’utilisation en chirurgie maxillo-faciale, les granules ont été empilés dans des tubes. Nous avons montré que l’architecture des empilements de granules dépendait de leur forme. L’empilement de granules commerciaux (contenant12,5g de β-TCP) mime l’architecture naturelle et les propriétés physiques de l’os. / The architecture of bone filling biomaterials has a real impact on cellular activity, vascularization and diffusion of growth factors. As a first step, different polystyrene (PS) scaffolds composed of aligned or random fibers were studied. They were non-biodegradable and could be used as supports for regeneration of large bone defects. We showed the in vitro cytocompatibility of the scaffolds by analyzing cell adhesion, proliferation and differentiation. Then, polystyrene scaffolds were enriched with β-TCP grains or gold nanoparticles. We implanted them in a model of critical size defect in mouse calvaria. Addition of β-TCP stimulated bone regrowth due to the high bioactivity of the ceramics. Scaffolds were biotolerated, fibers were encapsulated in the newly formed bone and also in a dense connective tissue. The gold nanoparticles immobilized on fibers migrated into the bone or were phagocytized. As a second step, different formulations of porous granules of β-TCP were analyzed by X-ray nanotomography. The macroporous architecture of granules varies inversely with the concentration of β-TCP. The internal faces howed a great heterogeneity of mineralization. Tomimic the conditions in maxillofacial surgery, granules were stacked in tubes. We have shown that the architecture of the granules depends on their shape.The stacks of commercial granules (containing 12.5 g ofβ-TCP) mimicked the natural architecture and physical properties of bone.

This report collects selected outstanding scientific and technological results obtained within the frame of the European project "FLASiC" (Flash LAmp Supported Deposition of 3C-SiC) but also other work performed in adjacent fields. Goal of the project was the production of large-area epitaxial 3C-SiC layers grown on Si, where in an early stage of SiC deposition the SiC/Si interface is rigorously improved by energetic electromagnetic radiation from purpose-built flash lamp equipment developed at Forschungszentrum Rossendorf. Background of this work is the challenging task for areas like microelectronics, biotechnology, or biomedicine to meet the growing demands for high-quality electronic sensors to work at high temperatures and under extreme environmental conditions. First results in continuation of the project work – for example, the deposition of the topical semiconductor material zinc oxide (ZnO) on epitaxial 3C-SiC/Si layers – are reported too.

En tredjedel av alla bypass-operationer leder till att kärlimplantaten slutar fungerar inom ettårs tid. En anledning till detta är bildandet av ogynnsam vävnad som sker i form av ärrbildning efter implantationen. Ärrvävnaden orsakar nya förträngningar vilket leder till ett försämrat blodflöde. Kärlimplantatet Y-graft har genom sin design som följer Murray´s lag, en naturlig blodflödesfördelning. Designen i form av ett Y har kunnat bekräftas vara fördelaktig då geometrin vid utflödet minskar risken för ärrbildning. Vad som saknas för att Y-graft ska kunna komma ut på marknaden är ett lämpligt material. Med detta som bakgrund uppkom syftet med litteraturstudien att undersöka vilka material meddokumenterad klinisk historik som är möjliga att använda vid textil tillverkning av Y-graft. Genom en gedigen litteratursökning med hjälp av sökverktyg som U.S. Food and Drug Administration (FDA) tillsammans med andra databaser inom de medicinska och materialtekniska områdena, har en förståelse skapats kring vilka material som används i medicintekniska produkter och som är möjliga kandidater till Y-graft. Litteraturstudien resulterade i att materialen polyetentereftalat, polybutentereftalat, polybutester polytetrafluoreten, polyester-, polyeter- och polykarbonatbaserade polyuretaner samt polypropen, polyeten, alfatisk polyamid och silke finns i godkända medicintekniska produkter på den amerikanska marknaden. De presenterade materialen har på så visdokumenterad klinisk historik och är lämpliga kandidater att använda vid textil tillverkning av Y-graft. De godkända materialkandidaterna som presenteras kan även beläggas medbiologiska polymerer för förbättrad biokompatibilitet. Materialkandidaterna har godkänts i medicintekniska produkter av U.S. Food and Drug Administration (FDA). Genom godkännandet har alla de presenterade materialen dokumenterad klinisk historik och är där med lämpliga kandidater att använda vid textiltillverkning av Y-graft. / One third of all bypass surgeries causes vascular implants to stop working within a year. A reason for this is the formation of unfavorable tissue that occurs in the form of scarring after implantation. The scar tissue causes new constrictions, which leads to impaired blood flow. The vascular implant Y-graft, by design follows Murray's law and therefore has a natural blood flow distribution. The design in the form of a Y has been confirmed to be advantageous. The Y geometry at the outflow reduces the risk of scarring. What is missing for Y-graft to be able to enter the market is a suitable material. With this as a background, the purpose of the literature study was to investigate which materials with documented clinical history can be used in textile production of Y-graft. Through a thorough literature search, using search tools like the U.S. Food and Drug Administration (FDA) together with other databases in the medical and material engineering fields, an understanding has been created about which materials are used in medical technology products and which are potential candidates for Y-graft. The literature study concluded that the materials polyethylene terephthalate, polybutheneterephthalate, polybutester polytetrafluoroethylene are found in approved medical technology products in the United States. Polyester, polyether and polycarbonate based polyurethanes and polypropylene, polyethylene, alphatic polyamide and silk are also found in the United States medical market. These presented materials thus have documented clinical history and are suitable candidates for use in textile manufacturing of Y-graft. The approved material candidates presented can also be coated with biological polymers for improved biocompatibility. The material candidates have been approved in medical technology products by the U.S. Food and Drug Administration (FDA). With this approval, all the presented materials have documented clinical history and are therefore suitable candidates to use when manufacturing Y-graft.

Gene therapy is a potential strategy for treatment of diseases caused by a gene defect. Recent studies are involved particulary in the cure of diseases caused by single gene defect (cystic fibrosis, haemophilia, muscular dystrophy etc.). Our work is part of a project aiming at developing ex vivo non-viral gene delivery systems that could be used for the treatment of ocular and cardiovascular diseases. The gene vectors are biodegradable polymeric carriers based on poly-α-amino acids. These polyplexes should transfect target cells which are supposed to be seeded on polyimide membranes. The biodegradable polymer membrane will be implanted into the retina or used as a coating for cardiovascular prosthesis. As a cover of the implantable membranes we used polymerized methacrylamide-modified gelatin forming hydrogels and mediating a growth support for transfected cells. We focus on material bio- and immunocompatibility/immunoacceptability. The results indicated a very good bio- and immunocompatibility of the gelatin B hydrogel both in vitro and in vivo. The gelatin B hydrogel did not cause erythrocytes lysis, stimulation of proliferation (spontaneous or mitogen-induced) of mouse or human lymphoid cells, neither production of cytokines or NO in vitro. Histological examination following subcutaneous...