The treatment of bone defects is facing the situation of lacking donations for autotransplantation. As a valid approach, scaffold-based tissue engineering combines the construction of well-defined porous scaffolds with advanced cell culturing technology to guide tissue regeneration. The role for the scaffold is to provide a suitable environment with a sufficient mechanical stiffness, supports for cell attachment, migration, nutrients and metabolite transport and space for cell remodeling and tissue regeneration. The random copolymers poly(L-lactide-co-ɛ-caprolactone) (poly(LLA-co-CL)) and poly(L-lactide-co-1,5-dioxepan-2-one) (poly(LLA-co-DXO)) have been successfully incorporated into 3D porous scaffolds to induce specific interactions with cells and direct osteogenic cell differentiation. In this thesis, these scaffolds have been modified in chemical and physical ways to map and understand requirements for bone regeneration. Scaffold functionalities and properties, such as hydrophilicity, stiffness, size/shape, and reproducibility, were studied. The hydrophilicity was varied by adding 3–20 % (w/w) Tween 80 to poly(LLA-co-CL) and poly(LLA-co-DXO) respectively, which resulted in contact angles from 35° to 15°. With 3 % Tween 80, the resultant mechanical and thermal properties were similar to pristine polymer materials. Tween 80 did not significantly influence cell attachment or proliferation but did stimulate the mRNA expression of osteogenetic markers. The surface functionality and mechanical properties were altered by introducing nanodiamond particles (n-DP) into poly(LLA-co-CL) scaffolds by means of surface physisorption or hybrid blending. Scaffold with n-DP physisorbed showed improved cell attachment, differentiation, and bone reformation. Hybrid n-DP/poly(LLA-co-CL) composites were obtained by direct blending of polylactide modified n-DP (n-DP-PLA) with poly(LLA-coCL). The n-DP-PLA was prepared by sodium hydride-mediated anionic polymerization using n-DP as the initiator. Prepared n-DP-PLA could be dispersed homogenously in organic solvents and blended with poly(LLA-coCL) solution. The n-DP-PLA particles were homogenously distributed in the composite material, which significantly improved mechanical properties. For comparison, the addition of benzoquinone-modified n-DP (n-DP-BQ) did not reinforce poly(LLA-co-CL). This indicated the importance of specific surface grafting, which determined different particle-polymer interactions. For the treatment of critical size defects, a large porous poly(LLA-co-CL) scaffold (12.5 mm diameter × 25 mm thickness) was developed and produced by molding and salt-leaching methods. The large porous scaffolds were evaluated in a scaffold-customized perfusion-based bioreactor system. It was obvious that the scaffold could support improved cell distribution and support the stimulation of human mesenchymal stem cell (hMSC) especially with dynamic flow in a bioreactor. To improve the scaffolding technique, a three-dimensional fiber deposition (3DF) technique was employed to build layer-based scaffolds. Poly(LLA-coCL) scaffolds produced by the 3DF method showed enhanced mechanical properties and a homogeneous distribution of human osteoblasts (hOBs) in the scaffolds. Although poly(LLA-co-CL) was thermally degraded, the degradation did not influence the scaffold mechanical properties. Based on the computerized design, a 3DF scaffold of amorphous copolymer poly(LLAco-CL) provides high-precision control and reproducibility. In summary, the design of porous scaffolds is one of the essential factors in tissue engineering as to mimicking the intrinsic extracellular environment. For bone tissue engineering, an optimized scaffold can maintain a contact angle greater than 35 degrees. Pristine or modified n-DP, introduced as an additive by surface physisorption or direct blending, can improve scaffold mechanical properties and cell response. Various sizes of scaffolds can be easily produced by a mold-mediated salt-leaching method. However, when 100 % reproducibility is required, the 3DF method can be used to create customizable scaffolds. / <p>QC 20140929</p>

MSc, Faculty of Science, University of the Witswatersrand, 2011 / The objective of this project is to understand the details of the electronic transport in low dimensional carbon structures at low temperatures as well as high magnetic fields. The emphasis is on the quasi-2 dimensional thin grain boundary regions of nanodiamond films and one dimensional carbon nanotubes. As such nitrogen “doped” and undoped nanodiamond films were synthesized by the hot filament chemical vapor deposition method (HFCVD). The films were micro-structurally and electrically characterized using several techniques such as Raman spectroscopy, scanning electron microscopy, transmission electron microscopy, atomic force microscopy and magnetoresistance (MR) measurements. The electronic transport properties were compared to the films deposited by microwave plasma enhanced chemical vapour deposition (MWCVD). The conductivity revealed a typical semiconducting and semi-metallic behavior for the HFCVD films depending on the nitrogen percentage in the chamber. The dephasing time of the electronic wave function was found to be weakly temperature dependant i.e. τ T-p with p < 1, a behavior reported in artificial superlattices. These results show potential application of these materials in novel nano-electronic devices. Previously the transport mechanism in nanodiamond films has been attributed to hopping conduction in the grain boundaries which is predominately disordered sp2 phases. Our studies on nanodiamond films have however shown different mechanisms in these films. We observed very little contribution from hopping and pronounced weak localization contributions in nanodiamond films. We thus establish the significance of tunneling transport in nanodiamond films. We also studied the electronic transport in films of metal filled multiwalled carbon nanotubes which show significant contribution from the hopping mechanism and a negative magnetoresistance at low fields that crosses over into positive MR at high magnetic fields.

The nitrogen-vacancy (NV) centre in diamond has proven to be an excellent tool to probe electro-magnetic fields and temperature. It has a number of unique features: High sensitivity and resolution, long coherence and lifetimes, the ability to operate from cryogenic temperatures to hundreds of Kelvin, chemical inertness and addressability via optics and microwaves. Recent progress includes the detection of NMR and spectroscopy of single proteins on a diamond surface and in-vivo temperature measurements. However, while the NV centre in bulk diamond has received a lot of attention, the nitrogen-vacancy in nanodiamond has not been investigated extensively due its widely seen inferior properties. It is only very recently that problems with the stability of photoluminescence and short coherence times have been overcome. The NV centre in nanodiamond is thus increasingly seen as an interesting tool for research requiring nanoscale sensors, e.g. in cells. The findings of this thesis facilitate applications of the NV centre in nanodiamond and demonstrate its high potential for future research. Most notably, the nuclear host spin, which is intrinsic to the point defect, can be used to enhance sensitivity and resolution of measurements. In addition, the sensitivity can be improved by time-tagging the emission from the NV centre. Furthermore, the graphite layer covering nanodiamonds can be removed by annealing. This does not have negative effects on the spin properties of the hosted NV centres but enables functionalisation of the surface and therefore advanced in-vivo measurements. Finally, the capabilities of the NV centre in nanodiamond in investigating the formation of magnetic domains are demonstrated at low temperatures. These results enable and motivate the use of the NV centre in nanodiamond for future research, most especially in biological systems.

Šio darbo tikslas buvo ištirti deimantų, apšaudytų 9 MeV galios protonais, ir nanodeimantų, paveiktų 40 keV galios helio jonais, elektrinį laidumą, bei jų Ramano sklaidos savybes. Gauti eksperimentiniai duomenys pavaizduoti diagramose ir palyginti su Frenkelio, šuolinio laidumo teorijomis. Palyginus eksperimentinius duomenis su teoriniais, priėjome išvados, kad nagrinėjant tūrinius deimantus geriausiai tinka Frenkelio laidumo mechanizmas, o nanodeimantus - šuolinio laidumo mechanizmas. Nustatytos terminės aktyvacijos energijos turiniame deimante ir nanodeimante. / The aim of this paper is to research diamonds and diamonds influenced by 9 MeV power protons. The impact of helium jones on nanodiamonds and nanodiamonds has also been investigated by studying both their electrical properties as well as the spread of Ramans spectroscopy. The received data have been showed on the diagrams. The data have been compared with the following theories of electrical conduction: Poole Frenkel‘s theory, Shottky‘s theory and hopping conduction theory. According to the research results, diamonds are better compared to Frenkel‘s theory, whereas nanodiamonds are better compared to hopping conduction theory. Activation energy is determined by received dependency parts.

In this dissertation, three aspects about surface and interface engineering of conjugated polymers and nanomaterials will be discussed. (i) There is a significant promise for electroactive conjugated polymers (ECPs) in applications of electrochemical devices including energy harvesting, electrochromic displays, etc. Among these, ECPs has also been developed as electroactive materials in electrochemical supercapacitors (ESCs). Compared with metal oxides, ECPs are attractive because they have good intrinsic conductivity, low band-gaps, relatively fast doping-and-undoping process, the ease of synthesis, and tunable electronic and structural properties through structural modifications. Here, Multiple-branch-chain 3,4-ethylenedioxythiophene (EDOT) derivatives was designed as crosslinkers in the co-electropolymerization of EDOT to optimize its morphology and improve the cycling stability of PEDOT in the supercapacitor applications. High-surface-area π-conjugated polymeric networks can be synthesized via the electrochemical copolymerization of the 2D (trivalent) motifs benzo[1,2-b:3,4-b’:5,6-b’’]trithiophene (BTT) and tris-EDOT-benzo[1,2-b:3,4-b’:5,6-b’’]trithiophene (TEBTT) with EDOT. Of all the material systems studied, P(TEBTT/EDOT)-based frameworks achieved the highest areal capacitance with values as high as 443.8 mF cm-2 (at 1 mA cm-2), higher than those achieved by the respective homopolymers (PTEBTT and PEDOT) in the same experimental conditions of electrodeposition (PTEBTT: 271.1 mF cm-2 (at 1 mA cm-2); PEDOT: 12.1 mF cm-2 (at 1 mA cm-2). (ii) In electrochemical process, the suitable choice of appropriate electrolytes to enlarge the safe working potential window with electrolyte stability is well known to improve ECPs’ performance in ESCs applications. Ionic liquids (ILs) are ion-composed salts and usually fluid within a wide temperature range with low melting points. There are many unique characteristics for these intrinsic ion conductors, including high ionic conductivity, wide electrochemical voltage windows in neutral conditions, fast ion mobility in redox reaction process (>10-14 m2 V-1 s-1), low vapor pressure, and environmental stability. These properties qualified ambient-temperature ILs to be applied as supporting medium for various devices and materials processing applications in both industry and academia, overcoming the limitation of volatile organic compounds (VOCs). Especially, ILs have been utilized as superior medium to electrodeposit metals, alloys, semiconductors and ECPs in the application of supercapacitors. Electropolymerization of EDOT and its derivative 4,4'-dimethoxy-3,3'-bithiophene (BEDOT) have been studied in three kinds of imidazolium-based ionic liquids and conducting salt in VOCs with different anions both as the growth medium and the supporting electrolyte, to assess the influence of these anions on their morphology and electrochemical activity. It is found these thiophene polymers grown in ILs with higher viscosity and lower diffusion shows much slower growth rate and orderly morphologies than in Tetrabutylammonium hexafluorophosphate (TBAPF6) dissolved in acetonitrile (ACN), and gives better electrochemical performance via cyclic voltammetry (CV) and galvanostatic charge-and-discharge (CD) studies. Polymers displayed multiple redox peaks in several cases, the possible reasons and origins are discussed. The synthesized polymer can be affected greatly by both the ILs with different anion/cation, and its mutal interation with targeted monomer.. As far as known, there is no systematic study on how the anions of ILs and common organic solution could play a role as a medium both for polymerization and post-polymerization electrolyte for PEDOT and its derivatives. This study can be used as an easy reference and provide experimental diagnositc data when selecting ionic liquids to investigate and optimize thiophene-based electrochemical systems, such as batteries and supercapactiors. (iii) Another aspect about interface chemistry of direct functionalization of nanodiamond with maleimide has also been addressed. Functional nanodiamonds are promising candidates for extensive practical applications in surface science, photonics and nanomedicine. Here, a protocol of direct functionalization is described by which maleimide-derivatized substituents can be appended to the outer shell of thermally annealed nanodiamonds through Diels-Alder reaction. This protocol can be carried out in room temperature, ambient atmosphere, without catalyst, and provide functionalized nanodiamonds with good solubility in organic solution. Also, this method can be applied for other maleimide derivatives,e.g.m aleimide-fluorescene, which can be applied in fluorescence labeling, sensing, and drug delivery. A series of techniques, especially Fourier transform infrared spectroscopy (FTIR), and Solid State Nuclear Magnetic Resonance (SS-NMR) was conducted for the analysis of surface chemistry and the investigation of the two-point binding strategy in details.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22465号 / 工博第4726号 / 新制||工||1738(附属図書館) / 京都大学大学院工学研究科分子工学専攻 / (主査)教授 関 修平, 教授 水落 憲和, 准教授 菅瀬 謙治, 教授 梶 弘典 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

Several disease processes taking place in the cells are characterized by an increase of the concentration of nucleic acids, in particular micro RNAs (miRNAs). A detection system that could selectively detect the increased presence of the miRNAs directly in the living cells in real time with nanoresolution is therefore highly desired. Fluorescent nanodiamond particles are considered promising candidates thanks to their biocompatibility, small size, allowing them to penetrate the cell membrane, and stable fluorescent defects in the crystal lattice, namely nitrogen-vacancy (NV) centres. The NV centres are the most studied colour centres of nanodiamonds due to their unique room-temperature optical properties, allowing for highly sensitive detection of changes in the magnetic field (magnetic noise) with quantum sensing techniques. For instance, the length of the T1 relaxation time NV electronic spin is greatly influenced by the presence of paramagnetic species, which causes a shortening of the T1 relaxation time depending on the proximity to the NV centres. However, for selective quantum sensing with nanodiamonds, the use of molecular transducers is necessary to bind targeted molecules with high specificity and allow their detection via the change of the NV spin properties. In this work,...

Current degradable orthopedic fixation devices do not typically facilitate tissue integration during healing. Proposed here is a novel combination of processing methods to enhance the tissue integration capability of degradable thermoplastics used in temporary orthopedic fixation devices. The provision of open pores in devices used to affix reconstructed hard tissues would allow for local cells to infiltrate during the healing process. Any openly porous structure is inherently weakened in comparison to its monolithic peers (i.e. decreased relative bulk modulus), such that the matrix materials must be made more resilient in keep the device from becoming friable. These processing methods aim to improve degradable surgical fixation devices at multiple levels of design: both through the inclusion of porous morphology, processing changes, and additives to regain mechanical integrity. Biomimetic pores are added for cellular infiltration by dissolving a porogen’s interpenetrating polymer network. The addition of open pores significantly reduces the bulk stiffness. More uniform phase separation has led to better pores, but the objects still need more resilience. Carbon nanomaterials are used to improve on the mechanics and surface chemistry of the polymer matrix material, composites of polylactide/nanodiamond are produced through cryogenic milling and solid state polycondensation. The addition of minute amounts of functionalized nanodiamond has remedied the brittle failure of the material, by cryogenic milling and solid state polycondensation of poly((D,L)lactide-co-glycolide) and hydroxyl functionalized detonation nanodiamonds. This composite has also demonstrated increased cytocompatability with 7F2 osteoblasts, as analyzed by cellular adhesion through fluorescence microscopy and alamar blue assay. / Bioengineering

Nanodiamonds are a promising platform for quantum technologies due to the combinations of their inherent properties and the properties of the fluorescent color centers hosted in diamond. They can be employed as quantum sensing devices with spatial resolution in the range of the nanometer and capable of withstanding harsh conditions while also being biocompatible, allowing applications with sensitive biological systems; but they also find application in quantum computing and photonics fields. For all these applications the central features are the properties of the photoluminescent color centers employed, the color centers on which this thesis is focused are the Nitrogen-Vacancy (NV) and Silicon-Vacancy (SiV) centers of diamond. Both centers are of high interest due to spin dependent properties of their fluorescent emission which can be accessed at room temperature. The development of quantum technologies based on such fluorescent nanodiamonds is stifled by the the lack of production techniques that can be easily scaled to industrial levels. In fact most of the more prominent techniques found in literature exhibit drawbacks both in terms of control of particle properties and of scalability. This thesis focuses on the synthesis of nanodiamonds by Pulsed Laser Ablation in Liquid, with particular interest in the possibility of producing continuously nanodiamonds containing NV and SiV centers. For the NV center the technique of choice have been Pulsed Laser Ablation in liquid nitrogen focusing on the yield of the process as the technique has already been experimentally validated. For the SiV centers the ablation process was performed in water and the graphite precursor have been substituted for a composite graphite and silicon carbide precursor.

A partir de l'étude des effets de la chimie de surface des Nanodiamants (NDs) sur leurs propriétés électroniques, cette thèse a permis la mise en évidence d'un effet thérapeutique des NDs sur des cellules humaines. En particulier, il a été montré que les NDs de détonation peuvent générer des radicaux libres oxygénés sous radiation ionisante, ce qui pourrait améliorer l'efficacité de certains traitements de radiothérapie actuels. Les échanges électroniques entre le coeur des NDs et leur environnement sont en effet favorisés après des traitements de surface, notamment d'hydrogénation et de graphitisation de surface. Les conditions expérimentales permettant d'obtenir des NDs hydrogénées (NDs-H) sous plasma d'hydrogène ont été optimisées sous ultravide, puis ont été utilisées pour préparer de grandes quantités de NDs-H sous forme pulvérulente. La même procédure a été appliquée pour la graphitisation de surface des NDs, en utilisant des recuits sous vide à haute température. L'effet de ces traitements de surface sur les propriétés d'interactions électroniques des NDs a été étudié après exposition à l'air ambiant, puis en dispersion dans l'eau. Ces traitements de surface assurent notamment un potentiel Zeta positif aux NDs, dont l'origine a été discutée. Enfin, les interactions des NDs avec plusieurs lignées de cellules tumorales humaines ont été étudiées et l'efficacité des NDs pour radiosensibiliser des cellules radiorésistantes sous irradiation gamma a été montrée, ouvrant de nouvelles perspectives d'applications des NDs en nanomédecine. . / In this thesis, a therapeutic effect of nanodiamonds (NDs) has been evidenced by investigating the role of NDs surface chemistry on their electronic properties. More precisely, the generation of reactive oxygen species from detonation NDs under ionizing radiation, which could improve current radiotherapy treatments, has been demonstrated. To this end, surface treatments facilitating electron transfer from NDs to their environment, namely hydrogenation and surface graphitization, were developed. Experimental conditions ensuring an efficient hydrogenation by hydrogen plasma were determined under ultrahigh vacuum, before being used to prepare large quantities of NDs in powder phase. A similar procedure was applied to the surface graphitization of NDs, performed by annealing under vacuum at high temperature. The impact of such surface treatments on the electronic interaction properties of NDs has been investigated under ambient air and after dispersion in water. These surface treatments induce a positive Zeta potential to NDs in water, which origin has been discussed. Finally, their interactions with human tumor cells were observed. Radiosensitization of tumor cells using NDs under gamma irradiation was demonstrated, opening new perspectives for NDs in nanomedicine.