Porous polyurethane coatings bonded onto surface-modified titanium substrates for the growth of an endothelial cell layer

Cardiovascular diseases refer to the class of diseases that involve the heart or blood vessels (arteries and veins). Examples of medical devices for treating the cardiovascular diseases include ventricular assist devices (VADs), artificial heart valves and stents. Metallic biomaterials such as titanium and its alloy are commonly used for ventricular assist devices. However, titanium and its alloy show unacceptable thrombosis, which represents a major obstacle to be overcome. Polyurethane (PU) polymer has better blood compatibility and has been used widely in cardiovascular devices. Thus one aim of the project was to coat a PU polymer onto a titanium substrate by increasing the surface roughness, and surface functionality. Since the endothelium of a blood vessel has the most ideal non-thrombogenic properties, it was the target of this research project to grow an endothelial cell layer as a biological coating based on the tissue engineering strategy. However, seeding endothelial cells on the smooth PU coating surfaces is problematic due to the quick loss of seeded cells which do not adhere to the PU surface. Thus it was another aim of the project to create a porous PU top layer on the dense PU pre-layer-coated titanium substrate. The method of preparing the porous PU layer was based on the solvent casting/particulate leaching (SCPL) modified with centrifugation. Without the step of centrifugation, the distribution of the salt particles was not uniform within the polymer solution, and the degree of interconnection between the salt particles was not well controlled. Using the centrifugal treatment, the pore distribution became uniform and the pore interconnectivity was improved even at a high polymer solution concentration (20%) as the maximal salt weight was added in the polymer solution. The titanium surfaces were modified by alkli and heat treatment, followed by functionlisation using hydrogen peroxide. A silane coupling agent was coated before the application of the dense PU pre-layer and the porous PU top layer. The ability of the porous top layer to grow and retain the endothelial cells was also assessed through cell culture techniques. The bonding strengths of the PU coatings to the modified titanium substrates were measured and related to the surface morphologies. The outcome of the project is that it has laid a foundation to achieve the strategy of endothelialisation for the blood compatibility of medical devices. This thesis is divided into seven chapters. Chapter 2 describes the current state of the art in the field of surface modification in cardiovascular devices such as ventricular assist devices (VADs). It also analyses the pros and cons of the existing coatings, particularly in the context of this research. The surface coatings for VADs have evolved from early organic/ inorganic (passive) coatings, to bioactive coatings (e.g. biomolecules), and to cell-based coatings. Based on the commercial applications and the potential of the coatings, the relevant review is focused on the following six types of coatings: (1) titanium nitride (TiN) coatings, (2) diamond-like carbon (DLC) coatings, (3) 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer coatings, (4) heparin coatings, (5) textured surfaces, and (6) endothelial cell lining. Chapter 3 reviews the polymer scaffolds and one relevant fabrication method. In tissue engineering, the function of a polymeric material is to provide a 3-dimensional architecture (scaffold) which is typically used to accommodate transplanted cells and to guide their growth and the regeneration of tissue. The success of these systems is dependent on the design of the tissue engineering scaffolds. Chapter 4 describes chemical surface treatments for titanium and titanium alloys to increase the bond strength to polymer by altering the substrate surface, for example, by increasing surface roughness or changing surface chemistry. The nature of the surface treatment prior to bonding is found to be a major factor controlling the bonding strength. By increasing surface roughness, an increase in surface area occurs, which allows the adhesive to flow in and around the irregularities on the surface to form a mechanical bond. Changing surface chemistry also results in the formation of a chemical bond. Chapter 5 shows that bond strengths between titanium and polyurethane could be significantly improved by surface treating the titanium prior to bonding. Alkaline heat treatment and H2O2 treatment were applied to change the surface roughness and the surface chemistry of titanium. Surface treatment increases the bond strength by altering the substrate surface in a number of ways, including increasing the surface roughness and changing the surface chemistry. Chapter 6 deals with the characterization of the polyurethane scaffolds, which were fabricated using an enhanced solvent casting/particulate (salt) leaching (SCPL) method developed for preparing three-dimensional porous scaffolds for cardiac tissue engineering. The enhanced method involves the combination of a conventional SCPL method and a step of centrifugation, with the centrifugation being employed to improve the pore uniformity and interconnectivity of the scaffolds. It is shown that the enhanced SCPL method and a collagen coating resulted in a spatially uniform distribution of cells throughout the collagen-coated PU scaffolds.In Chapter 7, the enhanced SCPL method is used to form porous features on the polyurethane-coated titanium substrate. The cavities anchored the endothelial cells to remain on the blood contacting surfaces. It is shown that the surface porosities created by the enhanced SCPL may be useful in forming a stable endothelial layer upon the blood contacting surface. Chapter 8 finally summarises the entire work performed on the fabrication and analysis of the polymer-Ti bonding, the enhanced SCPL method and the PU microporous surface on the metallic substrate. It then outlines the possibilities for future work and research in this area.

4-(4-Nitrobenzyl)pyridinium 5-nitrosalicylate

In the title salt, C12H11N2O2+·C7H4NO5-, the cations and anions interact through asymmetric cyclic pyridinium-carboxylate N-HO,O' hydrogen-bonding associations [graph set R12(4)], giving discrete heterodimers having weak cation-anion - aromatic ring interactions [minimum ring centroid separation = 3.7116 (9) Å]

Bis[2-(2,4-dinitrobenzyl)pyridinium] biphenyl-4,4'-disulfonate

In the structure of the title compound, the salt 2(C12H10N3O4+) (C12H8O6S2)2- . 3H2O, determined at 173 K, the biphenyl-4,4'-disulfonate dianions lie across crystallographic inversion centres with the sulfonate groups interacting head-to-head through centrosymmetric cyclic bis(water)-bridged hydrogen-bonding associations [graph set R4/4(11)], forming chain structures. The 2-(2,4-dinitrobenzyl)pyridinium cations are linked to these chains through N+-H...O(water) hydrogen bonds and a two-dimensional network structure is formed through water bridges between sulfonate and 2-nitro O atoms, while the structure also has weak cation--anion pi-pi aromatic ring interactions [minimum ring centroid separation 3.8441(13)A].

Hydrate stabilization in the three-dimensional hydrogen-bonded structure of the brucinium compound, bis(2,3-dimethoxy-10-oxostrychnidinium) biphenyl-4,4'-disulfonate hexahydrate

The crystal structure of the 2:1 proton-transfer compound of brucine with biphenyl-4,4’-disulfonate, bis(2,3-dimethoxy-10-oxostrychnidinium) biphenyl-4,4'-disulfonate hexahydrate (1) has been determined at 173 K. Crystals are monoclinic, space group P21 with Z = 2 in a cell with a = 8.0314(2), b = 29.3062(9), c = 12.2625(3) Å, β = 101.331(2)o. The crystallographic asymmetric unit comprises two brucinium cations, a biphenyl-4,4'-disulfonate dianion and six water molecules of solvation. The brucinium cations form a variant of the common undulating and overlapping head-to-tail sheet sub-structure. The sulfonate dianions are also linked head-to-tail by hydrogen bonds into parallel zig-zag chains through clusters of six water molecules of which five are inter-associated, featuring conjoint cyclic eight-membered hydrogen-bonded rings [graph sets R33(8) and R34(8)], comprising four of the water molecules and closed by sulfonate O-acceptors. These chain structures occupy the cavities between the brucinium cation sheets and are linked to them peripherally through both brucine N+-H...Osulfonate and Ocarbonyl…H-Owater to sulfonate O bridging hydrogen bonds, forming an overall three-dimensional framework structure. This structure determination confirms the importance of water in the stabilization of certain brucine compounds which have inherent crystal instability.

Low temperature synthesis of zeolite N from kaolinites and montmorillonites

Zeolite N was produced from a variety of kaolinites and montmorillonites at low temperature (b100 °C) in a constantly stirred reactor using potassic and potassic+sodic mother liquors with chloride or hydroxyl anions. Reactions were complete (N95% product) in less than 20 h depending on initial batch composition and type of clay minerals. Zeolite N with 1.0bSi/Alb2.2 was produced under these conditions using KOH in the presence of KCl, NaCl, KCl+NaCl and KCl+NaOH. Zeolite N was also formed under high potassium molarities in the absence of KCl. Zeolite synthesis was more sensitive to water content and temperature when sodium was used in initial batch compositions. Syntheses of zeolite N by these methods were undertaken at bench, pilot and industrial scales.

Low-dimensional hydrogen-bonded structures in the 1:1 and 1:2 proton-transfer compounds of 4,5-dichlorophthalic acid with the aliphatic Lewis bases triethylamine, diethylamine, n-butylamine and piperidine

The structures of proton-transfer compounds of 4,5-dichlorophthalic acid (DCPA) with the aliphatic Lewis bases triethylamine, diethylamine, n-butylamine and piperidine, namely triethylaminium 2-carboxy-4,5-dichlorobenzoate C~6~H~16~N^+^ C~8~H~3~Cl~2~O~4~^-^ (I), diethylaminium 2-carboxy-4,5-dichlorobenzoate C~4~H~12~N^+^ C~8~H~3~Cl~2~O~4~^-^ (II), bis(n-butylaminium) 4,5-dichlorophthalate monohydrate 2(C~4~H~12~N^+^) C~8~H~2~Cl~2~O~4~^2-^ . H~2~O (III) and bis(piperidinium) 4,5-dichlorophthalate monohydrate 2(C~5~H~12~N^+^) C~8~H~2~Cl~2~O~4~^2-^ . H~2~O (IV)have been determined at 200 K. All compounds have hydrogen-bonding associations giving in (I) discrete cation-anion units, linear chains in (II) while (III) and (IV) both have two-dimensional structures. In (I) a discrete cation-anion unit is formed through an asymmetric R2/1(4) N+-H...O,O' hydrogen-bonding association whereas in (II), one-dimensional chains are formed through linear N-H...O associations by both aminium H donors. In compounds (III) and (IV) the primary N-H...O linked cation-anion units are extended into a two-dimensional sheet structure via amide N-H...O(carboxyl) and ...O(carbonyl) interactions. In the 1:1 salts [(I) and (II)], the hydrogen 4,5-dichlorophthalate anions are essentially planar with short intramolecular carboxylic acid O-H...O(carboxyl) hydrogen bonds [O...O, 2.4223(14) and 2.388(2)A respectively]. This work provides a further example of the uncommon zero-dimensional hydrogen-bonded DCPA-Lewis base salt and the one-dimensional chain structure type, while even with the hydrate structures of the 1:2 salts with the primary and secondary amines, the low dimensionality generally associated with 1:1 DCPA salts is also found.

2-(2,4-dinitrobenzyl)pyridinium 2-hydroxy-3,5-dinitrobenzoate

In the structure of the title compound, the salt C12H10N3O4+ C7H3N2O72-, the cations and the anions are linked by a single N+-H...O(carboxyl) hydrogen bond, the discrete cation-anion unit having no intermolecular associations other than weak cation--anion aromatic ring pi--pi interactions [ring centroid separation, 3.7320(14)A] and a number of weak inter-unit aromatic C-H...O contacts.

Guanidinium phenylarsonate-guanidine-water (1/1/2)

In the structure of CH6N3+ C6H6AsO3- . CH5N3 . 2H2O, the phenylarsonate anion gives two R2/2(8) cyclic hydrogen-bonding interactions, one with a guanidinium cation, the other with a guanidine molecule. The anions are also bridged by the water molecules, one of which completes a cyclic R3/5(9) hydrogen-bonding association with the guanidinum cation, conjoint with one of the three R^2^~2~(8) associations about that ion, as well as forming an R1/2(6) cyclic association with the guanidine molecule. The result is a three-dimensional framework structure.

Guanidinium 3-nitrobenzoate

The structure of title compound, the anhydrous guanidinium salt, CH6N3+ C7H4NO4- shows a three-dimensional structure in which the guanidinium cation is involved in three cyclic R1/2(6) hydrogen-bonding associations with separate carboxylate O-acceptors. Further peripheral associations include a cyclic R2/1(4)cation--anion interaction, forming inter-linked undulating sheets in the framework structure.

Guanidinium 2-phenylacetate

In the structure of CH6N3+ C8H7O2-, the guanidinium cation gives three cyclic hydrogen-bonding interactions with O acceptors of three independent phenylacetate anions, one R2/2(8) and two R1/2(6), giving one-dimensional columnar structures which extend down the 4~2~ axis in the tetragonal cell. Within these structures there are 86.5A^3^ solvent accessible voids.

Development and synthesis of innovative approaches to the surgical assessment of articular cartilage degeneration

This research has established, through ultrasound, near infrared spectroscopy and biomechanics experiments, parameters and parametric relationships that can form the framework for quantifying the integrity of the articular cartilage-on-bone laminate, and objectively distinguish between normal/healthy and abnormal/degenerated joint tissue, with a focus on articular cartilage. This has been achieved by: 1. using traditional experimental methods to produce new parameters for cartilage assessment; 2. using novel methodologies to develop new parameters; and 3. investigating the interrelationships between mechanical, structural and molec- ular properties to identify and select those parameters and methodologies that can be used in a future arthroscopic probe based on points 1 and 2. By combining the molecular, micro- and macro-structural characteristics of the tissue with its mechanical properties, we arrive at a set of critical benchmarking parameters for viable and early-stage non-viable cartilage. The interrelationships between these characteristics, examined using a multivariate analysis based on principal components analysis, multiple linear regression and general linear modeling, could then to deter- mine those parameters and relationships which have the potential to be developed into a future clinical device. Specifically, this research has found that the ultrasound and near infrared techniques can subsume the mechanical parameters and combine to characterise the tissue at the molecular, structural and mechanical levels over the full depth of the cartilage matrix. It is the opinion in this thesis that by enabling the determination of the precise area of in uence of a focal defect or disease in the joint, demarcating the boundaries of articular cartilage with dierent levels of degeneration around a focal defect, better surgical decisions that will advance the processes of joint management and treatment will be achieved. Providing the basis for a surgical tool, this research will contribute to the enhancement and quanti�cation of arthroscopic procedures, extending to post- treatment monitoring and as a research tool, will enable a robust method for evaluating developing (particularly focalised) treatments.

Potential soil carbon sequestration in overgrazed grassland ecosystems

Excessive grazing pressure is detrimental to plant productivity and may lead to declines in soil organic matter. Soil organic matter is an important source of plant nutrients and can enhance soil aggregation, limit soil erosion, and can also increase cation exchange and water holding capacities, and is, therefore, a key regulator of grassland ecosystem processes. Changes in grassland management which reverse the process of declining productivity can potentially lead to increased soil C. Thus, rehabilitation of areas degraded by overgrazing can potentially sequester atmospheric C. We compiled data from the literature to evaluate the influence of grazing intensity on soil C. Based on data contained within these studies, we ascertained a positive linear relationship between potential C sequestration and mean annual precipitation which we extrapolated to estimate global C sequestration potential with rehabilitation of overgrazed grassland. The GLASOD and IGBP DISCover data sets were integrated to generate a map of overgrazed grassland area for each of four severity classes on each continent. Our regression model predicted losses of soil C with decreased grazing intensity in drier areas (precipitation less than 333 mm yr(-1)), but substantial sequestration in wetter areas. Most (93%) C sequestration potential occurred in areas with MAP less than 1800 mm. Universal rehabilitation of overgrazed grasslands can sequester approximately 45 Tg C yr(-1), most of which can be achieved simply by cessation of overgrazing and implementation of moderate grazing intensity. Institutional level investments by governments may be required to sequester additional C.

Optimal track access rights allocation for agent negotiation in an open railway market

In open railway access markets, a train service provider (TSP) negotiates with an infrastructure provider (IP) for track access rights. This negotiation has been modeled by a multi-agent system (MAS) in which the IP and TSP are represented by separate software agents. One task of the IP agent is to generate feasible (and preferably optimal) track access rights, subject to the constraints submitted by the TSP agent. This paper formulates an IP-TSP transaction and proposes a branch-and-bound algorithm for the IP agent to identify the optimal track access rights. Empirical simulation results show that the model is able to emulate rational agent behaviors. The simulation results also show good consistency between timetables attained from the proposed methods and those derived by the scheduling principles adopted in practice.

Coordinated road-junction traffic control by dynamic programming

This paper presents a novel approach to road-traffic control for interconnected junctions. With a local fuzzy-logic controller (FLC) installed at each junction, a dynamic-programming (DP) technique is proposed to derive the green time for each phase in a traffic-light cycle. Coordination parameters from the adjacent junctions are also taken into consideration so that organized control is extended beyond a single junction. Instead of pursuing the absolute optimization of traffic delay, this study examines a practical approach to enable the simple implementation of coordination among junctions, while attempting to reduce delays, if possible. The simulation results show that the delay per vehicle can be substantially reduced, particularly when the traffic demand reaches the junction capacity. The implementation of this controller does not require complicated or demanding hardware, and such simplicity makes it a useful tool for offline studies or realtime control purposes.