The ability to provide mass customised and biocompatible implants is increasingly important to improve the quality of life. Additive manufacturing (AM) techniques have obtained increasing popularity and selective laser melting (SLM), a metal-based AM technique with an ability to build complex and well defined porous structures, has been identified as a route to fabricate customised biomedical implants. Surface modification of an implant with a biomolecule is used to improve its biocompatibility and to reduce post-implant complications. In this thesis, the potential of a novel approach to use self-assembled monolayers to modify SLM fabricated surfaces with therapeutic drugs has been evaluated. Although there are numerous studies on the material development, process optimisation and mechanical testing of SLM fabricated parts, the surface chemistry of these parts is poorly understood. Initially, the surface chemistry of SLM as-fabricated (SLM-AF), SLM fabricated and mechanically polished (SLM-MP) and forged and mechanically polished (FGD-MP) parts made of Ti6Al4V was determined using an X-ray photoelectron spectrophotometer (XPS). Later the impact of laser power on the surface chemistry of the parts was also studied. A non-homogeneous surface chemistry was observed due to a change in the distribution of the alloying elements titanium, aluminium and vanadium on the surface oxide layer. Surface modification of the SLM fabricated component would be beneficial to obtain a homogenous surface chemistry, especially for biomedical application. Coating of self-assembled monolayers (SAMs) onto SLM fabricated Ti6Al4V structures was performed to modify their surface chemistry. 16-phosphanohexadecanoic acid monolayers (16-PhDA) were used to modify SLM-AF and SLM-MP surfaces. XPS and static water contact angle measurements confirmed the chemisorption of monolayers on these surfaces. The obtained results confirmed that SAMs were stable on the Ti6Al4V surface for over 28 days before its desorption. It was also witnessed that the stability of monolayers on the rough SLM-AF and smooth SLM-MP surfaces were not significantly different. Later, the 16-PhDA SAM coated Ti6Al4V SLM-MP surface was functionalised with a model drug, Paracetamol. An esterification reaction was performed to functionalise the phosphonic acid monolayers with Paracetamol. Surface characterisation revealed the sucessful attachment of Paracetamol to the SAMs. Bacterial infections from biomedical implants and surgical devices are reported to be a major problem in orthopaedic, dental and vascular surgery. Hence, to further explore the potential of the proposed method, Ciprofloxacin® a broad spectrum antibiotic was immobilised to the SAMs, previously adsorbed on the SLM-MP Ti6Al4V surfaces. Using the proposed approach, approximately 1.12 µg/cm2 of the drug was coated to the surface. Results showed that Ciprofloxacin® is highly stable under the oxidative conditions used in this study. Under in vitro condition, the drug was observed to release in a sustained manner. Antibacterial susceptibility tests revealed that the immobilised Ciprofloxacin® was therapeutically active upon its release. Thus, a novel methodology to fabricate customised and functionalised implants has been demonstrated for an improved biocompatibility and reduced post-implant complications.

Medical implant sensor that is used to monitor the human physiology signals is helpful to improve the quality of life and prevent severe result from the chronic diseases. In order to achieve this, the wireless implant communication link that delivers the monitored signal to a multiple antennas external device is an essential portion. However, the existing conventional narrow band Medical Implant Communications System (MICS) has low data rate because of the bandlimited channel is allocated. To improve the data rate in the radio frequency communication, ultra-wide band technology has been proposed. However, the ultra-wide band technology is relatively new and requires living human to be the test subject in order to validate the technology performance. In this condition, the test on the new technology can rise ethical challenge. As a solution, we improve the data rate in the conventional narrow band MICS. The improvement of data rate on the narrow band implies the information bandwidth is larger than the allocated channel bandwidth, and therefore the high frequency components of the information can loss. In this case, the signal suffers the intersymbol-interference (ISI). Instead of that, the multiple antennas external device can receive the signal from other transmitting implant sensor which has the same operating frequency. As a result, the signal is further hampered by co-channel interference (CCI). To recover the signal from the ISI and CCI, multiple-input multiple output (MIMO) blind equalization that has source separation ability can be exploited. Cross-Correlation Constant Modulus Algorithm (CC-CMA) is the conventional MIMO blind equalization algorithm that can suppress ISI and CCI and able to perform source separation. However, CC-CMA has only been analyzed and simulated in the modulation of Phase Shift Keying (PSK). The performance of CC-CMA in multi-modulus modulation scheme such as 4-Pulse-amplitude modulation (PAM) and 16-Quadrature amplitude modulation (QAM), which has higher data rate than PSK, has not been analyzed. Therefore, our work is to analysis and optimize CC-CMA on the multi-modulus modulation scheme. From our analysis, we found that the cost function of CC-CMA is biased cost function. Instead of that, from our simulation, CC-CMA introduces an unexpected shrinking effect whereby the amplitudes of the equalizer outputs have been reduced, especially in multi-modulus modulation scheme. This shrinking effect is not severe in PSK because the decision of a PSK symbol is based on phase, but not amplitude. Unfortunately, this is severe in multi-modulus modulation scheme. To overcome this shrinking effect in multi-modulus modulation scheme, we propose Cross-Independent Constant Modulus Algorithm (CI-CMA). Based on the convergence analysis, we identify the new optimum dispersion value and mixing parameter in CI-CMA. From the simulation results, we confirm that CI-CMA is able to perform equalization and source separation in the multi-modulus modulation scheme. In order to improve the steady state performance of CI-CMA, we perform the steady state mean square error (MSE) analysis of CI-CMA using the energy preservation theorem that was developed by Mai and Sayed in 2001, and our result is more accurate than the previous work. From our analysis, only the reduction in adaptation step size can reduce the steady state MSE, but it is well known that the MSE is indeed a tradeoff with the speed of convergence. Therefore without sacrificing convergence speed, our last effort is to propose hybrid algorithms. The hybrid algorithms are done by combining a new adaptive constant modulus algorithm (ACMA), a decision directed algorithm and a cross-correlation function. From the simulation results, we found that the hybrid algorithms can show low steady state error and thereby improve the reliability of the communication link. The main achievement of this thesis is the discovery of new dispersion value through the convergence analysis.

The aim of this thesis was to investigate a dual method of targeting cancer cells with a nanoparticle system containing both a thermoresponsive corona and folate tag. The nanoparticle system used a ‘hide-and-reveal’ motif whereby the folate tag would only be revealed above the transition temperature of the thermoresponsive corona. There were difficulties encountered during the synthesis of poly(lactide-co-glycolide) (PLGA) for the further polymerisation of the thermoresponsive copolymer therefore poly(lactide) (PLA) was synthesized as an alternative. The initial thermoresponsive polymer library synthesised (PLGA-b-poly((polypropylene glycol methacrylate)-stat-(oligoethylene glycol methacrylate))) when assembled into nanoparticles had a transition temperature (Tt) of 40 – 65 °C and thus did not have a low enough Tt for the cell studies. A second polymer library (PLA-b-P((diethylene glycol methacrylate)-stat-(oligoethylene glycol methacrylate)), PLA-b-P(DEGMA-stat-OEGMA)) when assembled into NPs had a Tt of between 28 – 78 °C when the DEGMA:OEGMA ratio was altered from 100:0 to 50:50. In addition to the thermoresponsive polymer library, three folate tagged amphiphilic polymers were synthesised. The polymers were PLA-b-polyethylene glycol (PLA-PEG) with a terminal folate. Each of the three PLA-PEGx polymers were synthesised with a different length of PEG, PEG450, PEG3k and PEG10k. A reproducible method of nanoparticle assembly was developed which produced nanoparticles of an average radius of ̴100 nm when PLA-b-P(DEGMA-stat-OEGMA) polymers were used. Three methods of controlling the overall aggregation temperature were put forward. By assembling NPs using one type of PLA-b-P(DEGMA-stat-OEGMA) the Tt of the NPs was dependent on the ratio of DEGMA:OEGMA. It was also possible to control the aggregation temperature by mixing two types of PLA-b-P(DEGMA-stat-OEGMA) polymers (provided the difference in DEGMA:OEGMA between the two polymers was between 0 – 10 %). In addition by mixing PLA-b-P(DEGMA-stat-OEGMA) preformed NPs the aggregation temperature could be controlled similar to that for polymer blend NPs. The NPs were tested in both MCF-7 and HCT116 cell lines and were shown to have no adverse effect on the cell metabolism or membrane integrity when the NP concentration was below 4 mg/mL. It was found that there was in increase in uptake of the thermoresponsive NPs when incubation temperature was above the NPs Tt. When the PEG450 and PEG3k linked folate was used an increased uptake was observed in MCF-7 cells however no difference in uptake was observed in HCT116 cell line. Overall the ‘hide-and-reveal’ motif on this NP system was shown to be successful in enhancing the uptake in folate receptor positive cells.

Recently, 3D printing has become popular in the field of tissue engineering, where materials and biology are combined with the aim of producing functional tissues for regenerative medicine therapies and for in vitro disease and toxicology models. However, current 3D printing techniques are not able to produce functional tissue-engineered constructs that are physiologically-relevant in the long-term. Challenges arise when combining desired mechanical properties with biological properties in a single construct. Often, cell-supportive materials lack mechanical stability and mechanically-robust materials are unable to support cell growth and function. In addition, many native tissues and organs are heterogeneous, with graded properties. The recapitulation of these factors will help to produce more physiologically-relevant tissue replacements and in vitro models with better predictability. This thesis seeks to combine biological and mechanical properties in a single core–shell strand: a mechanically-robust shell hydrogel encapsulating biologically active cell-laden core. This body of work has been split into three sections, the assessment of a hybrid material for use in the shell, the production of 3D printed constructs with core–shell strands, and the incorporation of gradients into these printed constructs. First, the mechanical properties of a poly(ethylene glycol) diacrylate (PEGDA)/alginate hybrid hydrogel was assessed using tensile testing. The hybrid hydrogels demonstrated synergy in their mechanical properties in a composition-dependent manner. In the second part of this thesis, a coaxial printing method was developed by combining a coaxial needle with a commercial extrusion-based 3D printer. Extruded strands displayed distinct core and shell regions and were able to support cell viability and function for up to 6 weeks. In the final part of this thesis, gradients were incorporated into the shell of core–shell strands. Both soluble factors gradients and stiffness gradients were characterised, and their longevity within these printed constructs was studied. In summary, core–shell strands have been shown to be a viable method to combine optimal mechanical and biological properties in a single construct. The core–shell technique could be made more complex with the addition of gradients, bringing printed constructs closer to their in vivo counterparts. With further research, this technique will help to create more physiologically-relevant tissue engineered constructs, which can drive research a step closer towards better disease models and future therapies.

This investigation was a development of a Personalized Relaxation Technique which was used in a comparative study of the effectiveness of this technique with the Relaxation Response, a popular relaxation method. The purpose of the study were (1) to design a Personalized Relaxation Technique and (2) to determine if this Personalized Relaxation Technique is as effective as the Relaxation Response. From the analysis of the data, no significant difference was found tin the three groups. Therefore, the two hypotheses were rejected. The conclusion of the study were (1) discrepancies exist in the literature concerning various relaxation techniques, (2) individual differences may be responsible for these discrepancies, and (3) fine tuning is needed between the theoretical concepts of a study on a relaxation technique and the research measures used to explore these concepts.

No description available.

Hypotension is a common finding in hospitalized, critically ill neonatal foals. Hypotension may be a function of low cardiac output or increased cardiac output and decreased systemic vascular resistance. In the first instance, treatment would include fluids and/or inotropes and in the second, fluids and/or vasopressors. Therefore, cardiac output measurements are expected to help guide the treatment of hypotension associated with critical illness and/or anesthesia in neonatal foals. However, a practical and safe method of measuring cardiac output has not been described for the foal. Lithium dilution, a new method of cardiac output determination not requiring cardiac catheterization, has recently been reported in adult horses. We compared this method to thermodilution in isoflurane anesthetized, 30 to 42 hour old foals and found good agreement (mean bias 0.0474L/min; limits of agreement -3.03 to 3.12) between the two methods in a range of cardiac outputs from 5.4 to 20.4 liters/min. The lithium dilution technique is a practical and reliable method of measuring cardiac output in anesthetized neonatal foals, and warrants investigation in critically ill conscious foals. / Master of Science

Bone repair is not always a spontaneous process. In some cases, intervention is required. This can involve the use of autograft but requires donor tissue. As a consequence there is a potential lack of material and donor site morbidity. Current alternatives are limited. There is a need for synthetic alternatives with a similar efficacy to autograft. Growth factors are currently being explored to address this need. A limiting factor to growth factor approaches are safety concerns and high costs. Both these problems stem from the fact that growth factors have short in vivo half lives and are administered at supraphysiological levels to maximise the duration of effect. There is a strong need for a growth factor delivery system that can maintain therapeutic doses and restrict administration to a specific location. This is currently limited by the fragile nature of growth factors. Microparticles were utilised. Microparticles were formed from poly(DL-lactic-coglycolic acid) with a poly(ethylene glycol) based plasticiser. This provided a method to modulate protein release based on the specific polymer formulation. Protein release was assessed with a model protein. The biological activities of released growth factors were assessed. Microparticles were fabricated for the delivery of vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and bone morphogenetic protein-2 (BMP-2) for release at time points conducive with osteogenic regeneration. A method was developed and validated to combine these microparticles with a suitable scaffold material. These composite scaffolds were developed with the intention of assessing controlled release of growth factors in a bone segmental defect. A method to fabricate microparticles with consistent size distributions and morphologies was developed. Formulations were tailored such that protein release from microparrticles could be from 2 days to 30 days. The biological activity of the released model protein was verified, as was the biological activity of released BMP-2. A method was devised to combine microparticles with a scaffold suitable for osteogenic regeneration of a segmental defect. This composite scaffold maintained a high level of porosity making it suitable for tissue ingress and growth factor diffusion. This study addresses key limitations to growth factor therapies. The sustained release of growth factors has the potential to mitigate dose-induced toxic effects as well as maintain therapeutic concentrations for longer periods. The nature of the delivery system delivers localised growth factors minimising the risk of systemic dosing leading to adverse reactions. This microparticle technology has potential in developmental research research as well as clinical therapies.

Forming tissues in the laboratory to replace diseased or dysfunctional tissue or act as models for drug treatment is the goal of tissue engineering. The large intestine epithelium (colon surface) is a tissue which could benefit from both diseased and non-diseased models for the purpose of tackling colon cancer causes and treatments. Scaffolds (cell supports) are a pivotal part in many tissue engineering strategies. This thesis describes the design and production of two separate scaffolds based on the degradable polymer poly(lactic-co-glycolic acid) (PLGA). The first was a two dimensional scaffold to mimic the intestinal basement membrane which was modified with an oxygen plasma. The changes to the surface due to plasma and the degradation properties of the scaffold were extensively studied with SEM, XPS, AFM and GPC. The data showed that the oxygen plasma induced surface porosity and associated changes to surface roughness. The surface chemistry as detected by XPS was unchanged by both plasma treatment and degradation in buffered solution. The plasma treatment did lead to a dramatic loss in molecular weight but the degradation profile of both the untreated and etched films was similar. Extensive cell studies with SEM, live/dead, alamarBlue and Hoechst DNA assays showed that intestinal cells on the plasma treated scaffold was enhanced in terms of morphology, metabolic activity and proliferation. Finally, a two dimensional co-culture model using epithelial and myofibroblasts cell lines on the modified PLGA scaffold was achieved. The second scaffold was a three dimensional scaffold bearing the crypt like architecture of the colon. An accurate mould produced through electron beam lithography using dimensions measured from mouse histological sections. PLGA particles were used to fill the mould and sintered to produce the scaffold. A unique cell seeding approach using cell sheets was used. The cell sheets were produced on plasma polymers of acrylic acid and the discharge power was shown to affect surface wettability, chemistry and cell viability. The cell sheet approach proved to enhance cell attachment to the scaffold compared to individual cell seeding. Finally, a bilayer scaffold with model protein to mimic Wnt protein presence in the lower half of the crypt was studied with ToF-SIMS.

<p>This licentiate thesis uses descriptive, mainly official,Swedish statistics to analyse industrial structure, productionand foreign trade in an industry that is traditionallydifficult to describe in numbers, that of medical devices. Forthe purposes of the thesis, the Swedish Medical Device industryis defined as companies classified in the SE-SIC manufacturingcodes 33101 (medical equipment and instruments, etc), 33102(dental products) and 35430 (invalid vehicles). Also otherbranches contribute, notably parts of SIC 51460 (wholesale inmedical equipment and pharmaceutical goods) and 73103 (medicalresearch and development) although their medical device volumecannot be specified. Additional items have been identified interms of specific product groups rather than as "belonging" toa specific SIC industrial code.</p><p>Taken together, this is considered to correspond reasonablywell to the scope of the field as defined by the Global MedicalDevice Nomenclature (GMDN), a new European standard forclassifying medical devices in a more generic way than do theEuropean Medical Device Directives (or other pieces oflegislation). No quantification according to GMDN can be madeas yet, however, as that requires changing reporting habits inindustry as well as in official statistical classification andnomenclature regimes.</p><p>With the manufacturing code SE-SIC 33101 as main object, thestudy for the first time presents data on the regionaldistribution, size classes of employment, company starting timeand company dynamics, in the form of entries to and exits fromthe code, over a six-year period. The latter analysis includesa follow-up of the "exits", some firms reappearing in otherparts of industry and others disappearing–surprisinglyfew among them being limited companies. Although this industryis comparatively mature, considerable mobility among themid-sized companies is indicated for reasons of real changes or(to some degree) factors inherent in the industrialclassification system. Some structural changes in companies inthe ≥50 employees bracket are identified. It is notedthat American actors, directly or indirectly, are increasinglyinvolved with the medical device industry in Sweden, and that anumber of technology-based companies that were started mostlyin the early eighties have recently reached the 50+ employeelevel.</p><p>The analysis of identifiable production and internationaltrade in medical devices spans a period of 17 years based onofficial statistics following the HS/CN nomenclatures. Adatabase has been built, bottom-up, from the 8-digit CN levelwith production, exports and imports values for close to 100items collected in 12 product groups, for presentation purposesgrouped under three main headings. Compound annual growth ratesfor the latter are presented for three five-year periods1985-2000, showing that Swedish production and exports have hadan overall growth of 10 per cent p.a. This has kept Swedenahead of the international overall growth of 6- 7 per cent p.a.in recent years, products in the main group "Aids&Implants" growing more than 20 per cent p.a. Growth rates inthe most recent five-year period are lower, however. Healthynet exports figures are presented, the figure for 2002nominally representing 40 per cent of the production value incurrent as well as constant prices.</p><p>Production figures are given at industry (local unit) levelas well as at product group level. The product-based figuresidentified for Production 2001 are estimated to SEK 13,3billion, Exports to SEK 13,7 billion and Imports to SEK 9,7billion. Figures for the Apparent Domestic Market arecalculated for the corresponding entities. It is obvious,however, that the statistics do not capture the real productionvalue as exports exceed production both at overall level and inmajor product groups, particularly those on a high systemstechnology level. The situation is not uncommon for a number ofreasons; further, cases in the statistics methodologyliterature confirm that medical instrument-related codes areliable to this phenomenon. Corrections, including adjustmentsof both production and exports values, are possible butdemanding already at one individual 4-digit HS/CN level. This,therefore, must be considered outside the scope of an academicstudy.</p><p>The basic tablework developed for this thesis will be madefreely available to external parties for their own use providedthe author, with contact details, is named as the source.(Processing for commercial purposes is not expected, however.)Any suggestions for improvements are welcomed.</p>