Dissertations / Theses on the topic 'Thermo-responsive hydrogels'

Différentes architectures macromoléculaires sensibles à la température, des copolymères linéaires greffés et des hydrogels, ont été développées et leur structure, leurs propriétés rhéologiques ainsi que leurs propriétés mécaniques ont été étudiées. Dans le cas des hydrogels, le phénomène de séparation de phase des segments thermosensibles conduit, en conditions isochores, à une augmentation de la rigidité et de l'élongation à la rupture ainsi qu'à de remarquables propriétés de fatigue. Ce renforcement est de plus totalement réversible en pilotant le processus d'association/dissociation des interactions avec la température. Nous montrons que la topologie des réseaux joue un rôle important sur les performances mécaniques des hydrogels et plus spécialement sur le mode de propagation de fissure au sein de la structure. A partir d'études structurales par diffusion de neutrons complétées par des expériences sous traction, différentes nanostructures sont proposées en fonction de la topologie. Enfin, ce concept de renforcement stimulable des propriétés mécaniques des hydrogels, induit par un mécanisme de micro-séparation de phase, a été élargi à d'autres réseaux polymères combinant des propriétés thermodynamiques de LCST et UCST
Thermo-responsive linear graft copolymers and hydrogels with different topologies have been designed and their nanostructure, their rheological properties as well as their tunable mechanical properties have been investigated. In the case of hydrogels, the self-assembly of the thermo-responsive sequences, which serve as secondary interactions, induces in isochoric conditions a strong enhancement of both stiffness and elongation at break, including also remarkable fatigue properties. Specifically, this reinforcement is totally reversible by switching on/off the associations. It is clearly shown that the topology of the network displays a crucial influence on the mechanical performance of hydrogels, especially the resistance to fracture. After a careful investigation of the structure by 2-D neutron scattering and tensile experiments, different nanostructures are proposed according to the topology. Finally, this concept of thermo-toughening of hydrogels through a controlled microphase separation has been extended to other polymeric networks combining LCST and UCST type polymers

Afin d’étudier spécifiquement le rôle des processus de séparation de phase sur le renforcement des propriétés mécaniques des hydrogels, nous avons travaillé en conditions isochores en développant des architectures non seulement thermosensibles mais également capables de conserver un taux d’hydratation très élevé de part et d’autre de la température de transition de phase. Pour cela, des gels greffés ont été préparés à partir d’un réseau réticulé de polymère hydrophile en introduisant des chaînes latérales thermosensibles de type LCST (PNIPAm). A partir de cette structure primaire, et en maintenant fixe le rapport massique des précurseurs hydrophile/thermosensible, nous montrons que les caractéristiques thermodynamiques de la transition de phase (température et variation d’enthalpie) restent pratiquement indépendantes de la masse molaire des greffons de même que leur processus d’auto-assemblage qui conduit à la formation de domaines cylindriques concentrés en greffons PNIPAm. A l’instar des matériaux composites, la formation de ces domaines denses en polymère stabilisés par des interactions physiques vont ainsi largement augmenter la rigidité des gels à haute température ainsi que leur résistance à la fracture en jouant le rôle de dissipateur d’énergie. Nous montrons que ce renforcement thermo-contrôlé augmente avec la taille des chaînes à LCST. Dans le cas où l’on fait varier la composition massique hydrophile/thermosensible, tout en maintenant constante la masse molaire des greffons, on démontre des comportements opposés à basse et haute températures avec de bonnes propriétés à froid lorsque le réseau est riche en matrice hydrophile réticulée (élasticité d’origine entropique) et de très bonnes propriétés à chaud lorsque le comportement mécanique est contrôlé par les domaines concentrées en greffons à LCST (élasticité d’origine enthalpique). Le phénomène de séparation de phase des greffons PNIPAm étant thermo-réversible par nature, et les interactions entre ces mêmes chaînes peu dynamiques à haute température, nous montrons que ces hydrogels greffés cumulent, respectivement, des propriétés d’auto-adhésion et de mémoire de forme. Enfin, en généralisant le processus de séparation de phase, nous montrons que le remplacement du réseau hydrophile par un réseau thermosensible de type UCST, permet d’obtenir un double phénomène de séparation de phase, à basse et à haute température. Si les températures de transition sont parfaitement corrélées avec les caractéristiques thermodynamiques de chacun des polymères, le renforcement mécanique dépend plus quant à lui des énergies d’interaction qui se développent lors de la transition de phase au sein du réseau à UCST (liaisons-H) ou entre les greffons à LCST (interactions hydrophobes + liaisons-H)
To specifically study the impact of phase-separation processes on hydrogels mechanical reinforcement, we worked under isochoric conditions developing architectures not only thermo-responsive but also able to keep a high level of hydration on both sides of the phase-separation temperature. For this purpose, grafted hydrogels have been formulated from a chemically cross-linked hydrophilic polymer network grafted with thermo-sensitive side-chains of LCST type (PNIPAm). From this primary structure and keeping constant the weight ratio between the hydrophilic and thermo-responsive parts, we demonstrate that the thermodynamic characteristics of the phase transition (enthalpy and temperature transitions) are only very weakly dependent on the molar mass of PNIPAm grafts as well as their self-assembly process which leads to cylindrical domains concentrated in PNIPAm grafts. Like the nanocomposite materials, the formation of these dense polymer domains stabilized by physical interactions highly enhances both the gels stiffness and fracture resistance at high temperature by dissipating energy. We show that this temperature-controlled reinforcement increases with the molar mass of the PNIPAm grafts. Varying the hydrophilic/thermo-responsive parts weight ratio while keeping constant the molar mass of the grafts, opposite behaviours at low and high temperatures were established. When the hydrophilic cross-linked network weight is high compared to the one of thermo-responsive grafts, the hydrogels exhibit good properties at low temperature (entropic elasticity) whereas at high temperature, their mechanical behaviour is controlled by the phase-separated domains concentrated in PNIPAm grafts (energetic elasticity). The phase-separation phenomenon of PNIPAm grafts being thermo-reversible by nature and the interactions between these chains being weakly dynamic at high temperature, we demonstrate that these grafted hydrogels exhibit both adhesive and shape-memory properties. Finally, expanding the phase-separation concept, we show that replacing the hydrophilic network by a UCST type thermo-responsive one allows getting a dual thermo-response with phase-separation occurring at both low and high temperatures. While these transition temperatures are perfectly correlated to the thermodynamic characteristics of each polymer, the mechanical reinforcement is more dependent on the energy due to the nature of interactions developing inside the UCST network (H-bonds) or between the LCST grafts (H-bonds and hydrophobic interactions) during the phase-separation process

This work describes the synthesis and characterization of stimuli-responsive polymers made by reversible addition-fragmentation chain transfer (RAFT) polymerization and the investigation of their self-assembly into “smart” hydrogels. In particular the hydrogels were designed to swell at low temperature and could be reversibly switched to a collapsed hydrophobic state by rising the temperature. Starting from two constituents, a short permanently hydrophobic polystyrene (PS) block and a thermo-responsive poly(methoxy diethylene glycol acrylate) (PMDEGA) block, various gelation behaviors and switching temperatures were achieved. New RAFT agents bearing tert-butyl benzoate or benzoic acid groups, were developed for the synthesis of diblock, symmetrical triblock and 3-arm star block copolymers. Thus, specific end groups were attached to the polymers that facilitate efficient macromolecular characterization, e.g by routine 1H-NMR spectroscopy. Further, the carboxyl end-groups allowed functionalizing the various polymers by a fluorophore. Because reports on PMDEGA have been extremely rare, at first, the thermo-responsive behavior of the polymer was investigated and the influence of factors such as molar mass, nature of the end-groups, and architecture, was studied. The use of special RAFT agents enabled the design of polymer with specific hydrophobic and hydrophilic end-groups. Cloud points (CP) of the polymers proved to be sensitive to all molecular variables studied, namely molar mass, nature and number of the end-groups, up to relatively high molar masses. Thus, by changing molecular parameters, CPs of the PMDEGA could be easily adjusted within the physiological interesting range of 20 to 40°C. A second responsivity, namely to light, was added to the PMDEGA system via random copolymerization of MDEGA with a specifically designed photo-switchable azobenzene acrylate. The composition of the copolymers was varied in order to determine the optimal conditions for an isothermal cloud point variation triggered by light. Though reversible light-induced solubility changes were achieved, the differences between the cloud points before and after the irradiation were small. Remarkably, the response to light differed from common observations for azobenzene-based systems, as CPs decreased after UV-irradiation, i.e with increasing content of cis-azobenzene units. The viscosifying and gelling abilities of the various block copolymers made from PS and PMDEGA blocks were studied by rheology. Important differences were observed between diblock copolymers, containing one hydrophobic PS block only, the telechelic symmetrical triblock copolymers made of two associating PS termini, and the star block copolymers having three associating end blocks. Regardless of their hydrophilic block length, diblock copolymers PS11 PMDEGAn were freely flowing even at concentrations as high as 40 wt. %. In contrast, all studied symmetrical triblock copolymers PS8-PMDEGAn-PS8 formed gels at low temperatures and at concentrations as low as 3.5 wt. % at best. When heated, these gels underwent a gel-sol transition at intermediate temperatures, well below the cloud point where phase separation occurs. The gel-sol transition shifted to markedly higher transition temperatures with increasing length of the hydrophilic inner block. This effect increased also with the number of arms, and with the length of the hydrophobic end blocks. The mechanical properties of the gels were significantly altered at the cloud point and liquid-like dispersions were formed. These could be reversibly transformed into hydrogels by cooling. This thesis demonstrates that high molar mass PMDEGA is an easily accessible, presumably also biocompatible and at ambient temperature well water-soluble, non-ionic thermo-responsive polymer. PMDEGA can be easily molecularly engineered via the RAFT method, implementing defined end-groups, and producing different, also complex, architectures, such as amphiphilic triblock and star block copolymers, having an analogous structure to associative telechelics. With appropriate design, such amphiphilic copolymers give way to efficient, “smart” viscosifiers and gelators displaying tunable gelling and mechanical properties.
Diese Arbeit befasst sich mit der RAFT-vermittelten Synthese und Charakterisierung von stimuli-empfindlichen Polymeren und ihrer Selbstorganisation zu „intelligenten” Hydrogelen. Die Hydrogele wurden so entwickelt, dass sie bei niedrigen Temperaturen stark quellen, bei Temperaturerhöhung jedoch reversibel in einem hydrophoben, kollabierten Zustand umgewandelt werden. Mit dem permanent hydrophoben Polystyrol (PS) und dem hydrophilen, thermisch schaltbaren Poly(methoxy-diethylen¬glycol-acrylat) (PMDEGA) als Bausteine, wurden unterschiedliche Gelierungsverhalten und thermische Übergangstemperaturen erreicht. Zur Synthese von Diblock-, symmetrischen Triblock- und dreiarmigen Sternblock-Copolymeren wurden neue funktionelle Kettenüberträger entwickelt. Diese gestatteten es, tert-butyl Benzoeester und Benzoesäure Endgruppen in die Polymere einzubauen, die einerseits eine effiziente Analyse mittels Routine 1H-NMR und darüber hinaus eine spätere Funktionalisierung der Endgruppen mit einer Fluoreszenzsonde ermöglichten. Da über PMDEGA kaum Daten vorlagen, wurde der Einfluss von Molekulargewicht, Endgruppen und Architektur auf das thermo-responsive Verhalten untersucht. Die speziellen Kettenüberträger ermöglichten es, gezielt hydrophobe wie hydrophile Endgruppen in die Polymere einzuführen. Die Trübungspunkte der wässerigen Lösungen von PMDEGA zeigten sich bis zu relativ hohen molaren Massen abhängig gegenüber allen untersuchten Variablen, nämlich dem Molekulargewicht, der Art und Zahl von Endgruppen. Durch Variation der diversen Parameter ließ sich die Schalttemperatur von PMDEGA in physiologisch relevanten Temperaturbereich von 20 bis 40 °C einstellen. Um die Polymere für einen zweiten Stimulus, nämlich Licht, empfindlich zu machen, wurden Azobenzol-funktionalisierte Acrylate synthetisiert und statistisch mit MDEGA copolymerisiert. Die Zusammensetzung der Polymeren wurde variiert und das isotherme Schalten der Löslichkeit durch Licht untersucht. Obwohl ein reversibles Schalten erreicht wurde, waren die Unterschiede zwischen den Trübungstemperaturen von UV-Licht bestrahlten und unbestrahlten Proben nur gering. Interessanterweise senkte die UV-Bestrahlung, d.h. ein erhöhter Gehalt von cis-Azobenzol-Gruppen, die Trübungstemperaturen herab. Dies ist genau umgekehrt als für azobenzolbasierten Systeme klassisch beschrieben. Die Gelbildung der verschiedenen Blockcopolymere von PS und PMDEGA wurde mittels Rheologie untersucht. Dabei traten deutliche Unterschiede auf, zwischen dem Gelierungsverhalten der Diblockcopolymere, die nur einen PS Block enthalten, dem der symmetrischen Triblockcopolymere, die zwei assoziative PS Endblöcken besitzen, und dem der Sternpolymere, die drei assoziative PS Blöcke aufweisen. Unabhängig von der Länge des hydrophilen Blockes, bilden Diblockcopolymere des Typs PS11-PMDEGAn keine Gele, sondern selbst bei hohen Konzentrationen von 40 Gew. % Lösungen. Im Gegensatz dazu bildeten die Triblockcopolymere des Typs PS8-PMDEGAn-PS8 Gele bei niedrigen Temperaturen, vereinzelt schon ab 3.5 wt. %. Mit steigender Temperatur, tritt bereits unterhalb des Trübungspunktes für diese Systeme ein Gel-Sol Übergang auf. Der Gel-Sol Übergang bewegt sich zu höheren Temperaturen mit steigende Länge des hydrophilen inneren Blocks. Dieser Trend verstärkt sich mit zunehmender Anzahl von Endblöcken und deren Länge. An der Trübungstemperatur veränderten sich die mechanischen Eigenschaften aller Gele signifikant und die gebildeten flüssigen Dispersionen ließen sich reversibel beim Abkühlen wieder zu Gel schalten. Diese Arbeit, zeigt dass PMDEGA ein bei niedrigen Temperaturen gut wasserlösliches, nicht-ionisches, thermisch-schaltbares und wahrscheinlich biokompatibles Polymer ist. PMDEGA liest sich einfach mittels den RAFT-Verfahren molekular maßschneiden, mit spezifischen Endgruppen und komplexen Polymerarchitekturen. Solche amphiphilen Triblock- und Sternblock-Copolymeren hoher Molmasse, wirken als assoziative Telechele. Daher eigenen sich bei entsprechendem Design diese amphiphilen Blockcopolymere als effiziente Verdicker und Gelbildner mit einstellbaren mechanischen und thermischen Eigenschaften.

Localized drug delivery is emerging as an effective technique due to its ability to administer therapeutic concentrations and controlled release of drugs to cancer sites in the body. It also prevents the contact of harsh chemotherapy drugs to healthy regions in the body that otherwise would become exposed to current treatments. This study reports on a model chemotherapy drug delivery system comprising non-ionic surfactant vesicles (niosomes) packaged within a temperature-sensitive chitosan network. This smart packaging, or package-within-a package system, provides two distinct advantages. First, the gel prevents circulation of the niosomes and maintains delivery in the vicinity of a tumor. Secondly, the chitosan network protects the niosomes against fluctuations in tonicity, which affects delivery rates. Tonicity is the sum of the concentrations of the solutes which have the capacity to exert an osmotic force across the membrane. Release rates were monitored from both bare niosomes alone and niosome-embedded, chitosan networks. It was observed that chitosan networks prolonged delivery from 100 hours to 55 days in low ionic strength environment and pH conditions similar to a tumor site. The primary effect of chitosan is to add control on release time and dosage, and stabilize the niosomes through a high ionic strength surrounding that prevents uncontrolled bursting of the niosomes. Secondary factors include cross-link density of the chitosan network, molecular weight of the individual chitosan polymers, dye concentration within the niosomes, and the number density of niosomes packaged within the chitosan network. Each of these factors can be altered to fine-tune release rates. Release rate experiments were conducted with 5,6-carboxyfluorescein, a fluorescent dye and chemotherapeutics paclitaxel and carboplatin. In vitro studies showed a preferential affinity of the smart packaged system to ovarian carcinoma cell line OV2008 as compared to normal epithelial cell lines of Ilow and MCC3. Further, feasibility of the drug delivery system was evaluated in vivo. Toxicity studies revealed that the system was non-toxic and feasible in vivo. The final outcome of this study includes tuning of the variables mentioned above that will contribute to the development of low cost and improved methods for drug delivery with application to intracavitary ovarian cancer treatment and other types of cancer

碩士
高雄醫學大學
醫藥暨應用化學研究所
96
A new kind of thermo-responsive biological hydrogel scaffolds was synethized in this studies. First, P(NiPAAm-MAA) hydrogels were polymerized with N-isopropyl acryamide (NiPAAm) and Methylacrylic acid (MAA). Then the P(NiPAAm-MAA)-PEG-HA hydrogels were synthesized with Hyaluronic acid (HA) by cross-linking the Polyethyl glycol bisamine (PEG-diamine). The new hydrogles combined both advantages of NiPAAm and HA which including better mechanical properties, biodegradable and biocompatibility. The characteristic of P(NiPAAm-MAA)-PEG-HA hydrogels were evaluated by H-NMR, FT-IR and Viscometer. The swelling ratio and water content of hydrogels were measured in different pH value at 37℃. And the lower critical solution temperature (LCST) of the hydrogels was measured with different temperature by Viscometer. The hydrogels were immersed in PBS (pH=7.4) at 37℃ to observed the change of weight lost. The surface of hydrogels after freeze-drying were observed by SEM. Finally, MTS activity assay of hydrogels cultured for 24, 48, 72 hours. The results showed that the hydrogels exhibited a LCST at 34℃ and swelling ratio was between 4-8 times and water content was between 73-93%. The swelling ratio and water content depended on the pH value of PBS solution. MTS activity culture prove that the hydrogels were no toxicity. So The new thermo-responsive P(NiPAAm-MAA)-PEG-HA hydrogels will have great potential applications in tissue engineering.

碩士
長庚大學
生化與生醫工程研究所
94
Abstract In this study we examined the behavior of freshly isolated rat hepatocytes cultivated within thermal-sensitive hydrogels based on N-isopropylacrylamide (NIPAAm) and acrylic (AAc). The hydrogel scaffold can mimic the in vivo extracellular matrix and provide a three-dimensional environment for cell proliferation and differentiation. Hepatocyes were encapsulated in NIPAAm-AAc copolymer hydrogel beads and cultured in the rotation cell culture system (RCCS) that could provide a microgravity cell culture environment. Factors such as rotation speed of RCCS, hydrogel encapsulation, cell numbers in hydrogel beads, culture condition (static or dynamic), and medium oxygen level were studied for its influence on cell aggregate size, albumin secretion rate, and urea production rate. Hydrogel copolymer modified with galactosamine, which provides a galactose moiety for recognition by hepatocytes surface receptors, was found to drastically up-regulate the metabolic functions of hepatocytes.

碩士
國立成功大學
化學工程學系
103
In this study, we reported the preparation of thermo-responsive supramolecular hydrogels via inclusion complexation between cyclodextrins (CDs) and peptide amphiphiles (PAs). Alkylamine were used as the macroinitiator of ring-opening polymerization (ROP) to synthesize PAs. CDs threaded onto alkyl chain and form inclusion complex. The network structure of hydrogels was composed of hydrophobic interactions between alkyl chain and inner cavity of CDs, hydrogen bonding between CDs and side chain of PAs. The gel-sol transition temperature and gelation concentration were tuned by alkyl chain length, type of amino acids and CDs, the molar ratio of CDs and PAs. The secondary structure of peptides was mainly random coil. C12Thr20+α-CD hydrogels formed lamellar packing and the one bilayer thickness decreased with increasing temperature. The intelligent hydrogels could be promising in tissue engineering.

In the first part of this work, silica nanoparticles and alternative or additional filler phases were incorporated into hydrogels based on the temperature-sensitive poly(N- isopropylacrylamide) (PNIPAm). Nano-SiO2-filled porous PNIPAm hydrogels with an enhanced force response (up to 100 g) to temperature stimuli were obtained by increasing several times the pore wall thickness, which was achieved via reducing the solvent (porogen) content during the gels' cryo-synthesis. A similar optimization of the force response was also carried out for analogous gels reinforced by nano-TiO2, in which the reinforcing effect of the filler is weaker. Partial intercalation of amylopectin starch into divinyl-crosslinked bulk as well as porous PNIPAm gels several times improved their extensibility. In case of starch-rich bulk gels, a very fast and extensive one-way deswelling in response to increased temperature was achieved (re-swelling upon cooling is much slower), which is attributed to specific properties of the starch-PNIPAm interface. In doubly-filled bulk PNIPAm/nano-SiO2/starch gels, a very strong synergic reinforcing effect of both fillers is observed, due to specific hydrogen bridging between the three phases. Highly porous cryogels based on PNIPAm/nano- SiO2/starch displayed a highly improved extensibility...

abstract: Solar energy is leading in renewable energy sources and the aspects surrounding the efforts to harvest light are gaining importance. One such aspect is increasing the light absorption, where heliotropism comes into play. Heliotropism, the ability to track the sun across the sky, can be integrated with solar cells for more efficient photon collection and other optoelectronic systems. Inspired by plants, which optimize incident sunlight in nature, several researchers have made artificial heliotropic and phototropic systems. This project aims to design, synthesize and characterize a material system and evaluate its application in a phototropic system. A gold nanoparticle (Au NP) incorporated poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was synthesized as a photo-thermo-responsive material in our phototropic system. The Au NPs generate heat from the incident via plasmonic resonance to induce a volume phase change of the thermo-responsive hydrogel PNIPAAm. PNIPAAm shrinks or swells at temperature above or below 32°C. Upon irradiation, the Au NP-PNIPAAm micropillar actuates, specifically bending toward the incident light and precisely following the varying incident angle. Swelling ratio tests, bending angle tests with a static incident light and bending tests with varying angles were carried out on hydrogel samples with varying Au NP concentrations. Swelling ratios ranging from 1.45 to 2.9 were recorded for pure hydrogel samples and samples with very low Au NP concentrations. Swelling ratios of 2.41 and 3.37 were calculated for samples with low and high concentrations of Au NPs, respectively. A bending of up to 88° was observed in Au NP-hydrogel pillars with a low Au NP concentration with a 90° incident angle. The light tracking performance was assessed by the slope of the pillar Bending angle (response angle) vs. Incident light angle plot. A slope of 1 indicates ideal tracking with top of the pillar being normal to the incident light, maximizing the photon absorption. Slopes of 0.82 and 0.56 were observed for the low and high Au NP concentration samples. The rapid and precise incident light tracking of our system has shown the promise in phototropic applications.
Dissertation/Thesis
Masters Thesis Materials Science and Engineering 2016

No
Microcarrier cell culture systems provide an attractive alternative to the conventional monolayer cell culture for cell amplification, due to their high surface area-to-volume ratio. Unlike enzymatic methods for removing cells from microcarriers after cell culture, which can lead to irreversible damage of the cells, microcarriers which release cells by temperature adjustment have been developed. This was achieved by grafting a temperature-responsive polymer, poly(N-isopropylacrylamide) (PNIPAAm), on the microcarrier surface. This review comprehensively presents various methods to prepare such thermo-responsive microcarriers based on PNIPAAm. These methods include the grafting-to technique, grafting-from technique, grafting-through technique, along with methods leading to PNIPAAm hydrogel beads, seeded polymerization, and non-covalent adsorption. The methods for controlling PNIPAAm grafting density, molecular weight and molecular architecture are also outlined. Further, the efficiency of cell attachment, proliferation and thermally-induced detachment of such thermo-responsive microcarriers is introduced and compared. (C) 2015 Elsevier Ltd. All rights reserved.
EPSRC

碩士
國立臺灣師範大學
化學系
94
Abstract Inorganic nanomaterials that interface with biological systems have recently attracted widespread interests in biomedical application. In this paper, we employ gold nanorods to be template to synthesize silica-coat or polymer-coating gold nanorods. The part of silica-coating gold nanorods is successful to synthesize uniform silica-coating gold nanorods. Furthermore, we can synthesis not only silica nanocapsule by dissolving gold nanorod completely, but hollow silica-coating gold nanorods. The part of polymer-coating gold nanorods, we can successfully synthesize thermo-responsive hydrogel-coated gold nanorods, poly(N-isopropylacrylamide-coAcrylic acid ) (p(NIPAAm-co-AAc)). Thermo-responsive hydrogel are observed that they are deswelling , then release water in hysrogel when heated above its lower critical solution temperature (LCST). Utilizing this property, we encapsulated drug in this material. The temperature of this material is raised when gold nanorods in core absorb laser of specific wavelength. It can be control drug release when temperature above LCST of hydrogel. At present,we use different gold nanorods that have different specific wavelength, it can successfully control release of different drug by absorbing laser of different wavelength.

碩士
長庚大學
化工與材料工程學系
99
This paper focuses on developing a novel, simple, time-saving route to magnetic stimuli-responsive nano-latex particles preparation with a core-shell structure. The iron oxide (Fe3O4)-containing poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAAm-co-AAc)) nano-hydrogel particles were fabricated via a soap polymerization method. The magnetic nano-particles (MNPs) were stabilized with the AAc to form cores, which served as nuclei for further polymerization with NIPAAm and AAc monomers. The P(NIPAAm-co-AAc) shell layer exhibited thermo-sensitive (ascribed from NIPAAm) and pH-responsive (ascribed from AAc) properties. The samples synthesized using different preparation methods were characterized for their particle sizes, LCSTs, chemical compositions and magnetisms. The results showed that MNPs were embedded in nano-gel particles from the Fourier transform infrared (FTIR) spectra, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analyzer (TGA) and superconducting quantum interference device magnetometer (SQUID). The AAc was copolymerized with the NIPAAm, as revealed from the FTIR and XPS spectra. Increasing the AAc content increased the latex nano-particle lower critical solution temperature (LCST) due to more hydrophilic segments in the copolymer. The transmittance electron micrographs revealed that the resulting nano-hydrogel particles exhibited a core-shell structure with a diameter of 200 nm. In an acidic solution (of pH 5), the thermal responses were observed whereas no significant changes were detected in alkaline solutions (at pH 9). A polymer propagation mechanism is proposed to illustrate the time-dependent particle sizes during the reaction course. The magnetic thermo-responsive nano-latex particles can be synthesized for use in numerous fields, such as biomedical applications.

碩士
高雄醫學大學
醫藥暨應用化學研究所
98
Tissue engineering has proved to be one of the most promising therapies for bone fracture defects [1]. This new paradigm requires scaffolds that balance temporary mechanical function with mass transport to aid biological delivery and bone repair [1]. It has been reported that of HAp/TCP (hydroxyapatite/tricalcium phosphate) promotes the new bone formation from in vivo experiments [2]. While, porous bioceramic acts as a scaffold for the rapid ingrowths of vascularized connective tissue and bone. According to the current literature the optimal pore size is estimated to be 80~160 [3] or 500~1000 ?慆 [4]. Besides the strength acts the performance of porous hydroxyapatite ceramics. However, the compressive strength of cancellous bone will be ~5 MPa [5]. Several technologies exist today to manufacture strong and reliable porous ceramics. But these scaffolds prepared methods maybe can have a controllable pore size, interconnected pores, and desired geometry but often poor mechanical strength for load-bearing applications [5]. Besides, statins have potent compounds that inhibit cholesterol synthesis in the liver and have been reported to induce bone formation, both in tissue culture and in rats and mice [6, 7]. However, the high concentration of simvastatin have rhabdomyolysis side effect [6]. In this study, we report a novel technique that integrates the thermo-responsive hydrogel technique with porogen polymer method to prepare HAp/TCP porous scaffolds with improved mechanical strength and controllable porous structure. The hypothesis is that thermo-responsive hydrogel will shrink with the temperature increasing; then the function can be regarded as isostatic cold pressing (ICP) effect before ceramic sintering. Meanwhile, we filled appropriate simvastatin in porous bioceramic to obtain optimal release profile.

碩士
高雄醫學大學
生理及分子醫學研究所
99
The lesion of articular cartilage often results in progressive deterioration and eventual osteoarthritis. Current clinical used strategies meet difficulties to restore the native structure of cartilage. Tissue engineering has been suggested to provide more advantages over the strategies used clinically nowadays. It consists of three major components: cells, biomaterials and environmental factors. Adipose-derived stem cells (ADSCs) has been proposed as a better cell source because of ease of harvest, high proliferative property and possessing multilineage differentiation potential. Our previous study showed that hyaluronan (HA), as a micro-environmental factor, can both initiate and enhance chondrogenesis of ADSCs, and subsequently facilitate hyaline cartilaginous matrix formation. The thermoresponsive Poly(N-isopropyl- acrylamide) (PNIPAAM) hydrogel is an injectable biomaterial at room temperature and shifts to solid phase over 32℃, which may be a suitable cell carrier for tissue engineering. However, NIPAAM monomer has cytotoxicity and PNIPAAM has no chondroinductive property for ADSCs. Accordingly, we hypothesized that HA-modified PNIPAAM hydrogel (HA-PNIPAAM) may improve cell viability of ADSCs and enhance ADSCs’ chondrogenesis for articular cartilage tissue engineering. The aim of this study is to develope the HA-PNIPAAM and to test the effect on chondrogenic differentiation of ADSCs. The effects of PNIPAAM, HA and PNIPAAM composite (HA-PNIPAAM-CP) and HA-crosslinked PNIPAAM (HA-PNIPAAM-CL) on cell viability, chondrogenic differentiation as well as cartilaginous matrix formation of rabbit ADSCs (rADSCs) in vitro or in vivo were tested. Our result from Fourier-transformed infrared absorption spectroscopy confirmed that the HA functional groups crosslinked onto the chemical structure of PNIPAAM in HA-PNIPAAM-CL. The thermoresponsive property of HA-PNIPAAM-CP and HA-PNIPAAM-CL were not changed by HA composite or modification, respectively. The SEM observation of PNIPAAM, HA-PNIPAAM-CP and HA-PNIPAAM-CL was symmetric sheet, non-symmetric and honey-comb like structure, respectively. The swelling ratio and shrinking ratio showed that PNIPAAM after HA composition or modification had significantly higher swelling ratio, and lower shrinking ratio of PNIPAAM. The results showed that the rADSCs cultured in HA-PNIPAAM-CP and HA-PNIPAAM-CL induced cell aggregation on day 1 and day 5 in comparison to the cells cultured in PNIPAAM, but only HA-PNIPAAM-CL maintained cell survival after day 5 culture by Live and dead stain or MTS assay. The sGAG synthesis showed the rADSCs cultured in HA-PNIPAAM-CP and HA-PNIPAAM-CL had strong sGAG level by Alcian blue staining at day 5 and 7. The quantification of sGAG showed that a significant difference was found in rADSCs cultured in HA-PNIPAAM-CL compared to PNIPAAM or HA-PNIPAAM-CP on day 5 and 7 by DMMB assay. The HA-PNIPAAM-CL showed greater chondrogenic gene expression (type II collagen and aggrecan) than in PNIPAAM or HA-PNIPAAM-CP from day 5 to 7 of culture by real-time polymerase chain reaction. In vivo study, the H&E staining results showed that the rADSCs cultured HA-PNIPAAM-CL that had been implanted for 3 weeks in rabbit joint cavity had obvious tissue and cellular matrix formation than other the two groups. The rADSCs cultured in HA-PNIPAAm-CL and HA-PNIPAAm-CP had higher sGAG and type II collagen staining in comparison to the cells cultured in PNIPAAm by Safranin-O-fast green stain and immunohistochemistry stain (IHC), respectively. For cell tracking, the cartilaginous tissue from the rADSCs cultured in PNIPAAM, HA-PNIPAAM-CP and HA-PNIPAAM-CL showed obvious cells with fluorescent red by confocal microscopy. This newly developed thermoresponsive HA-PNIPAAM-CL demonstrated good cytocompatibility and chondrogenic differentiation property. We suggest that the copolymer may be used as cell vehicles for cartilage tissue engineering.

博士
國立臺灣大學
化學研究所
102
The studies of this thesis are divided into two parts: Section I describes that a novel nanothermometer Thermo-3HF with self-calibrating ratiometric fluorescence readout was designed and synthesized by taking advantage of the fluorescence nature of 3-hydroxyflavones. Thermo-3HF consists of thermoresponive NIPAM unit, crosslinker MBAM unit, and environmentally-sensitive 3-HFAM fluorescent unit in a ratio of 100: 1: 1. Within a sensing temperature range of 33 to 41 oC, the fluorescence color of the Thermo-3HF nanothermometer changes from blue to green. The ratiometric change magnitude is about 8.7-fold, rendering the visual differentiation of color by the naked eyes feasible. Section II describes the early-stage result of developing multifunctional drug delivery nanovectors. A reaction-based cross-linked polymeric nanoprobe HP-3HF with self-calibrating ratiometric fluorescence readout to selectively detect H2O2 is reported. HP-3HF nanoprobe is fabricated by hydrophobic H2O2-reactive boronic ester groups DCBE, crosslinker units HQBAE, and environmental-sensitive 3-HFAM fluorophores via miniemulsion polymerization. Upon the treatment of H2O2, the boronic esters in the polymer are cleavaged to form hydrophilic alcohols, subsequently leading to a hydrophobic/hydrophilic transition. Covalently linked 3-hydroxyflavones manifest the change in polarity as a ratiometric transition from green to blue, accompanied by a 500-fold increase in its volume. In addition, HP-3HF nanoprobe has been exploited for ratiometric glucose sensing by monitoring the H2O2 generated from the oxidation of glucose via glucose oxidase, and thus successfully distinguished between normal and pathological levels of glucose. After completing these tests, the potential of HP-3HF as a H2O2-responsive drug delivery nanovector for the remedy of cancers or inflammation-related diseases has been explored. The assessments of cellular uptake and cytotoxicity analysis of HP-3HF nanovector in RAW 264.7 macrophages confirm that HP-3HF is biocompatible and easy to enter into cells. The drug-releasing experiment of Nile Red-encapsulated HP-3HF (NR@HP-3HF) upon H2O2 stimulation also shows that HP-3HF is feasible as a controlled drug delivery nanovector.