Thermoplastic bioactive composite – with special reference to dissolution behaviour and tissue response

Bioactive glasses are surface-active ceramic materials which support and accelerate bone growth in the body. During the healing of a bone fracture or a large bone defect, fixation is often needed. The aim of this thesis was to determine the dissolution behaviour and biocompatibility of a composite consisting of poly(ε-caprolactone-co-DL-lactide) and bioactive glass (S53P4). In addition the applicability as an injectable material straight to a bone defect was assessed. In in vitro tests the dissolution behaviour of plain copolymer and composites containing bioactive glass granules was evaluated, as well as surface reactivity and the material’s capability to form apatite in simulated body fluid (SBF). The human fibroblast proliferation was tested on materials in cell culture. In in vivo experiments, toxicological tests, material degradation and tissue reactions were tested both in subcutaneous space and in experimental bone defects. The composites containing bioactive glass formed a unified layer of apatite on their surface in SBF. The size and amount of glass granules affected the degradation of polymer matrix, as well the material’s surface reactivity. In cell culture on the test materials the human gingival fibroblasts proliferated and matured faster compared with control materials. In in vitro tests a connective tissue capsule was formed around the specimens, and became thinner in the course of time. Foreign body cell reactions in toxicological tests were mild. In experimental bone defects the specimens with a high concentration of small bioactive glass granules (<45 μm) formed a dense apatite surface layer that restricted the bone ingrowth to material. The range of large glass granules (90-315 μm) with high concentrations formed the best bonding with bone, but slow degradation on the copolymer restricted the bone growth only in the superficial layers. In these studies, the handling properties of the material proved to be good and tissue reactions were mild. The reactivity of bioactive glass was retained inside the copolymer matrix, thus enabling bone conductivity with composites. However, the copolymer was noticed to degradate too slowly compared with the bone healing. Therefore, the porosity of the material should be increased in order to improve tissue healing.

Development of porous glass-fiber reinforced composite for bone implants. Evaluation of antimicrobial effect and implant fixation

Cranial bone reconstructions are necessary for correcting large skull bone defects due to trauma, tumors, infections and craniotomies. Traditional synthetic implant materials include solid or mesh titanium, various plastics and ceramics. Recently, biostable glass-fiber reinforced composites (FRC), which are based on bifunctional methacrylate resin, were introduced as novel implant solution. FRCs were originally developed and clinically used in dental applications. As a result of further in vitro and in vivo testing, these composites were also approved for clinical use in cranial surgery. To date, reconstructions of large bone defects were performed in 35 patients. This thesis is dedicated to the development of a novel FRC-based implant for cranial reconstructions. The proposed multi-component implant consists of three main parts: (i) porous FRC structure; (ii) bioactive glass granules embedded between FRC layers and (iii) a silver-polysaccharide nanocomposite coating. The porosity of the FRC structure should allow bone ingrowth. Bioactive glass as an osteopromotive material is expected to stimulate the formation of new bone. The polysaccharide coating is expected to prevent bacterial colonization of the implant. The FRC implants developed in this study are based on the porous network of randomly-oriented E-glass fibers bound together by non-resorbable photopolymerizable methacrylate resin. These structures had a total porosity of 10–70 volume %, of which > 70% were open pores. The pore sizes > 100 μm were in the biologically-relevant range (50-400 μm), which is essential for vascularization and bone ingrowth. Bone ingrowth into these structures was simulated by imbedding of porous FRC specimens in gypsum. Results of push-out tests indicated the increase in the shear strength and fracture toughness of the interface with the increase in the total porosity of FRC specimens. The osteopromotive effect of bioactive glass is based on its dissolution in the physiological environment. Here, calcium and phosphate ions, released from the glass, precipitated on the glass surface and its proximity (the FRC) and formed bone-like apatite. The biomineralization of the FRC structure, due to the bioactive glass reactions, was studied in Simulated Body Fluid (SBF) in static and dynamic conditions. An antimicrobial, non-cytotoxic polysaccharide coating, containing silver nanoparticles, was obtained through strong electrostatic interactions with the surface of FRC. In in vitro conditions the lactose-modified chitosan (chitlac) coating showed no signs of degradation within seven days of exposure to lysozyme or one day to hydrogen peroxide (H2O2). The antimicrobial efficacy of the coating was tested against Staphylococcus aureus and Pseudomonas aeruginosa. The contact-active coating had an excellent short time antimicrobial effect. The coating neither affected the initial adhesion of microorganisms to the implant surface nor the biofilm formation after 24 h and 72 h of incubation. Silver ions released to the aqueous environment led to a reduction of bacterial growth in the culture medium.

Effects of composite casein and [beta]-lactoglobulin genotypes on renneting properties and composition of bovine milk by assuming an animal model

Selostus: Kaseiinien yhdistelmägenotyyppien ja [beta]-laktoglobuliinin genotyyppien vaikutus maidon juoksettumisominaisuuksiin ja koostumukseen

Development of Craniofacial Bone Defect Reconstruction Implant Based on Fibre-Reinforced Composite with Photopolymerisable Resin Systems. Experimental studies in vitro and in vivo.

Reconstruction of defects in the craniomaxillofacial (CMF) area has mainly been based on bone grafts or metallic fixing plates and screws. Particularly in the case of large calvarial and/or craniofacial defects caused by trauma, tumours or congenital malformations, there is a need for reliable reconstruction biomaterials, because bone grafts or metallic fixing systems do not completely fulfill the criteria for the best possible reconstruction methods in these complicated cases. In this series of studies, the usability of fibre-reinforced composite (FRC) was studied as a biostable, nonmetallic alternative material for reconstructing artificially created bone defects in frontal and calvarial areas of rabbits. The experimental part of this work describes the different stages of the product development process from the first in vitro tests with resin-impregnated fibrereinforced composites to the in vivo animal studies, in which this FRC was tested as an implant material for reconstructing different size bone defects in rabbit frontal and calvarial areas. In the first in vitro study, the FRC was polymerised in contact with bone or blood in the laboratory. The polymerised FRC samples were then incubated in water, which was analysed for residual monomer content by using high performance liquid chromatography (HPLC). It was found that this in vitro polymerisation in contact with bone and blood did not markedly increase the residual monomer leaching from the FRC. In the second in vitro study, different adhesive systems were tested in fixing the implant to bone surface. This was done to find an alternative implant fixing system to screws and pins. On the basis of this study, it was found that the surface of the calvarial bone needed both mechanical and chemical treatments before the resinimpregnated FRC could be properly fixed onto it. In three animal studies performed with rabbit frontal bone defects and critical size calvarial bone defect models, biological responses to the FRC implants were evaluated. On the basis of theseevaluations, it can be concluded that the FRC, based on E-glass (electrical glass) fibres forming a porous fibre veil enables the ingrowth of connective tissues to the inner structures of the material, as well as the bone formation and mineralization inside the fibre veil. Bone formation could be enhanced by using bioactive glass granules fixed to the FRC implants. FRC-implanted bone defects healed partly; no total healing of defects was achieved. Biological responses during the follow-up time, at a maximum of 12 weeks, to resin-impregnated composite implant seemed to depend on the polymerization time of the resin matrix of the FRC. Both of the studied resin systems used in the FRC were photopolymerised and the heat-induced postpolymerisation was used additionally.

Simulation of Boundary Layers and Heat Transfer in the Entrance Region of Pipes

The study of fluid flow in pipes is one of the main topic of interest for engineers in industries. In this thesis, an effort is made to study the boundary layers formed near the wall of the pipe and how it behaves as a resistance to heat transfer. Before few decades, the scientists used to derive the analytical and empirical results by hand as there were limited means available to solve the complex fluid flow phenomena. Due to the increase in technology, now it has been practically possible to understand and analyze the actual fluid flow in any type of geometry. Several methodologies have been used in the past to analyze the boundary layer equations and to derive the expression for heat transfer. An integral relation approach is used for the analytical solution of the boundary layer equations and is compared with the FLUENT simulations for the laminar case. Law of the wall approach is used to derive the empirical correlation between dimensionless numbers and is then compared with the results from FLUENT for the turbulent case. In this thesis, different approaches like analytical, empirical and numerical are compared for the same set of fluid flow equations.

MOCVD growth andproperties of GaN and AlGaN layers

In this work GaN and AlGaN layers were grown by metal-organic chemical vapor deposition (MOCVD) on sapphire substrates. The research was carried out at Micro and Nanoscience Laboratory of Helsinki University of Technology. The objective of this thesis is the study of MOCVD technique for the growth of GaN and AlGaN films and optimization of growth parameters in purpose to improve crystal quality of the films. The widely used two-step and the new multistep methods have been used for GaN, AlGaN MOCVD growth on c-plane sapphire. Properties of the GaN and AlGaN layers were studied using in-situ reflectance monitoring during MOCVD growth, atomic force microscopy and x-ray diffraction. Compared to the two step method, the multistep method has produced even better qualities of the GaN and AlGaN layers and significant reduction of threading dislocation density.

Kulutus- korroosionkestävien materiaalien laserpinnoitus

Diplomityössä tutkitaan kulutus- ja korrosionkestävien materiaalien laserpinnoitusta. Laserpinnoituksessa sulatetaan uutta materiaalia työkappaleen pintaan lasersäteen avulla. Tarkoituksena on yleensä parantaa pinnan korroosion, kulumisen tai pintapaineen kestävyyttä. Laserpinnoitukseen liittyy useita etuja verrattuna konventionaalisiin päällehitsausprosesseihin. Työssä tutkittavat pinnoitemateriaalit ovat kobolttipohjaiset Stellite 1 ja Stellite 6, työkaluteräkset WR 4 ja WR 6 sekä metallimatriisikomposiitti Anval50/50+30 % Cr3C2. Pinnoitettavat perusaineet ovat hiiliteräs Fe 52, ruostumaton teräs AISI 316 ja valurauta GRP 500. Työn tavoitteena on löytää kunkin pinnoite/perusaine-yhdistelmän pinnoitusparametrit. Pinnoituskokeissa käytettiin LTKK:n 6 kW:n CO2-laseria. Pinnoitetuille koekappeleille tehtiin kovuusmittaukset ja kulutuskokeet. Pinnoitteiden mikrorakenteet analysoitiin ja sekoittumisasteet laskettiin. Virheitä tutkittiin silmämääräisesti sekä radiografisella kuvauksella. Optimiparametreja pinnoitemateriaaleille ei löydetty. Pinnoitteiden sekoittumisasteet muodostuivat suuriksi liiallisen lasertehon ja/tai huonon lisäaineen kohdistuksen vuoksi. Suuri sekoittuminen alensi pinnoitteiden kovuutta ja kulumiskestävyyttä. Pinnoitusparametreja arvioidaan koetulosten perusteella ja niille annetaan korjausehdotuksia. Lopuksi esitetään suosituksia tutkimusprojektin jatkotoimille.

Fiber-reinforced Composite as Oral Implant Material. Experimental studies of glass fiber and bioactive glass in vitro and in vivo

Fiber-reinforced composite as oral implant material: Experimental studies of glass fiber and bioactive glass in vitro and in vivo Department of Prosthetic Dentistry and Biomaterials Science, Institute of Dentistry, University of Turku, Turku, Finland 2008. Biocompatibility and mechanical properties are important variables that need to be determined when new materials are considered for medical implants. Special emphasis was placed on these characteristics in the present work, which aimed to investigate the potential of fiber-reinforced composite (FRC) material as an oral implant. Furthermore, the purpose of this study was to explore the effect of bioactive glass (BAG) on osseointegration of FRC implants. The biocompatibility and mechanical properties of FRC implants were studied both in vitro and in vivo. The mechanical properties of the bulk FRC implant were tested with a cantilever bending test, torsional test and push-out test. The biocompatibility was first evaluated with osteoblast cells cultured on FRC substrates. Bone bonding was determined with the mechanical push-out test and histological as well as histomorplanimetric evaluation. Implant surface was characterized with SEM and EDS analysis. The results of these studies showed that FRC implants can withstand the static load values comparably to titanium. Threaded FRC implants had significantly higher push-out strength than the threaded titanium implants. Cell culture study revealed no cytotoxic effect of FRC materials on the osteoblast-like-cells. Addition of BAG particles enhanced cell proliferation and mineralization of the FRC substrates The in vivo study showed that FRC implants can withstand static loading until failure without fracture. The results also suggest that the FRC implant is biocompatible in bone. The biological behavior of FRC was comparable to that of titanium after 4 and 12 weeks of implantation. Furthermore, addition of BAG to FRC implant increases peri-implant osteogenesis and bone maturation.

Coatings on Composites

Polymer based composite materials coated with thin layers of wear resistant materials have been proposed as replacements for steel components for certain applications with the advantage of reduced mass. Magnetron sputtered coatings can be successfully deposited on composite materials. Nevertheless there are number of issues which must be addressed such as limited temperature, which the composite can withstand because of the epoxy binder which is used, the adhesion of the coating to the composite and the limited mechanical support, the hard coating can obtain from the relatively soft epoxy. We have investigated the deposition of chromium nitride, titanium carbide and titanium doped DLC coatings on carbon fibre reinforced composites and various polymers. The adhesion of the coatings has been studied by the pull-off adhesion tester. In general, the failure mechanism has been noticed to be due to the cohesive failure for a wide range of conditions. The wear behavior of the coatings has been noticed to be complicated. Wear tests on coated composites have shown that where the reinforcing fibres are near the surface, the composite samples do not perform well due to breakage of the fibres from the polymer matrix. A fibre free surface has been noticed to improve the wear resistance.

Non-resorbable glass fibre-reinforced composite with porous surface as bone substitute material: Experimental studies in vitro and in vivo focused on bone-implant interface

The development of load-bearing osseous implant with desired mechanical and surface properties in order to promote incorporation with bone and to eliminate risk of bone resorption and implant failure is a very challenging task. Bone formation and resoption processes depend on the mechanical environment. Certain stress/strain conditions are required to promote new bone growth and to prevent bone mass loss. Conventional metallic implants with high stiffness carry most of the load and the surrounding bone becomes virtually unloaded and inactive. Fibre-reinforced composites offer an interesting alternative to metallic implants, because their mechanical properties can be tailored to be equal to those of bone, by the careful selection of matrix polymer, type of fibres, fibre volume fraction, orientation and length. Successful load transfer at bone-implant interface requires proper fixation between the bone and implant. One promising method to promote fixation is to prepare implants with porous surface. Bone ingrowth into porous surface structure stabilises the system and improves clinical success of the implant. The experimental part of this work was focused on polymethyl methacrylate (PMMA) -based composites with dense load-bearing core and porous surface. Three-dimensionally randomly orientated chopped glass fibres were used to reinforce the composite. A method to fabricate those composites was developed by a solvent treatment technique and some characterisations concerning the functionality of the surface structure were made in vitro and in vivo. Scanning electron microscope observations revealed that the pore size and interconnective porous architecture of the surface layer of the fibre-reinforced composite (FRC) could be optimal for bone ingrowth. Microhardness measurements showed that the solvent treatment did not have an effect on the mechanical properties of the load-bearing core. A push-out test, using dental stone as a bone model material, revealed that short glass fibre-reinforced porous surface layer is strong enough to carry load. Unreacted monomers can cause the chemical necrosis of the tissue, but the levels of leachable resisidual monomers were considerably lower than those found in chemically cured fibre-reinforced dentures and in modified acrylic bone cements. Animal experiments proved that surface porous FRC implant can enhance fixation between bone and FRC. New bone ingrowth into the pores was detected and strong interlocking between bone and the implant was achieved.

Microwave Slot Transmission Line Filled with Ferroelectric and Ferromagnetic Layers

Now when the technology is fast developing it is very important to investigate new hybrid structures. One way is to use ferrite ferroelectric layered structures. Theoretical and experimental investigation of such structures was made. These structures have advantages of both layers and it is possible to tune the behavior of this structure by external electric and magnetic field. But these structures have some disadvantages connected with presence of thick ferroelectric layer. One way to overcome this problem is to use slotline. So this is another new way to create hybrid ferrite ferroelectric structures, but it is needed to create new theory and find experimental proof that the behavior of these structures can be tuned with external magnetic and electric fields.

Crystallization characteristics of bioactive glasses

Bioactive glasses are excellent candidates for implant materials, because they can form a chemical bond to bone or guide bone growth, depending on the glass composition. Some compositions have even shown soft tissue attachment and antimicrobial effects. So far, most clinical applications are based on monoliths, plates and particulates of different grain sizes. There is a growing interest in special products such as porous implants sintered from microspheres and fibers drawn from preforms or glass melts. The viscosity range at which these are formed coincides with the crystallization temperature range for most bioactive glasses, thus complicating the manufacturing process. In this work, the crystallization tendency and its kinetics for a series of glasses with their compositions within the range of bioactivity were investigated. The factors affecting crystallization and how it is related to composition were studied by means of thermal analysis and hot stage microscopy. The crystal compositions formed during isothermal and non-isothermal heat treatments were analyzed with SEM-EDXA and X-ray diffraction analysis. The temperatures at which sintering and fiber drawing can take place without interfering with crystallization were determined and glass compositions which are suitable for these purposes were established. The bioactivity of glass fibers and partly crystallized glass plates was studied by soaking them in simulated body fluid (SBF). The thickness of silica, calcium and phosphate rich reaction layers on the glass surface after soaking was used as an indication of the bioactivity. The results indicated that the crystallization tendencies of the experimental glasses are strongly dependent on composition. The main factor affecting the crystallization was found to be the alkali oxide content: the higher the alkali oxide content the lower the crystallization temperature. The primary crystalline phase formed at low temperatures in these glasses was sodium calcium silicate. The crystals were found to form through internal nucleation, leading to bulk crystallization. These glasses had high bioactivity in vitro. Even when partially crystalline, they formed typical reaction layers, indicating bioactivity. In fact, sodium calcium silicate crystals were shown to transform in vitro into hydroxyapatite during soaking. However, crystallization should be avoided because it was shown to retard dissolution, bioactivity reactions and complicate fiber drawing process. Glass compositions having low alkali oxide content showed formation of wollastonite crystals on the surface, at about 300°C above the glass transition temperature. The wide range between glass transition and crystallization allowed viscous flow sintering of these compositions. These glasses also withstood the thermal treatments required for fiber drawing processing. Precipitation of calcium and phosphate on fibers of these glasses in SBF suggested that they were osteoconductive. Glasses showing bioactivity crystallize easily, making their hot working challenging. Undesired crystallization can be avoided by choosing suitable compositions and heat treatment parameters, allowing desired product forms to be attained. Small changes in the oxide composition of the glass can have large effects and therefore a thorough understanding of glass crystallization behavior is a necessity for a successful outcome, when designing and manufacturing implants containing bioactive glasses.

Bonding of Composite Resin to Alumina and Zirconia Ceramics with Special Emphasis on Surface Conditioning and Use of Coupling Agents

Dental oxide ceramics have been inspired by their biocompability and mechanical properties which have made durable all-ceramic structures possible. Clinical longevity of the prosthetic structures is dependent on effective bonding with luting cements. As the initial shear bond strength values can be comparable with several materials and procedures, long-term durability is affected by ageing. Aims of the current study were: to measure the shear bond strength of resin composite-to-ceramics and to evaluate the longevity of the bond; to analyze factors affecting the bond, with special emphasis on: the form of silicatization of the ceramic surface; form of silanization; type of resin primer and the effect of the type of the resin composite luting cement; the effect of ageing in water was studied regarding its effect to the endurance of the bond. Ceramic substrates were alumina and yttrium stabilized zirconia. Ceramic conditioning methods included tribochemical silicatization and use of two silane couplings agents. A commercial silane primer was used as a control silane. Various combinations of conditioning methods, primers and resin cements were tested. Bond strengths were measured by shear bond strength method. The longevity of the bond was generally studied by thermocycling the materials in water. Additionally, in one of the studies thermal cycling was compared with long-term water storaging. Results were analysed statistically with ANOVA and Weibull analysis. Tribochemical treatment utilizing air pressure of 150 kPa resulted shear bond strengths of 11.2 MPa to 18.4 MPa and air pressure of 450 kPa 18.2 MPa to 30.5 MPa, respectively. Thermocycling of 8000 cycles or four years water storaging both decreased shear bond strength values to a range of 3.8 MPa to 7.2 MPa whereas initial situation varied from 16.8. Mpa to 23.0 MPa. The silane used in studies had no statistical significance. The use of primers without 10-MDP resulted spontaneous debonding during thermocycling or shear bond strengths below 5 MPa. As conclusion, the results showed superior long-term bonding with primers containing 10-MDP. Silicatization with silanizing showed improved initial shear bond strength values which considerably decreased with ageing in water. Thermal cycling and water storing for up to four years played the major role in reduction of bond strength, which could be due to thermal fatigue of the bonding interface and hydrolytic degradation of the silane coupled interface.

Printed low-voltage organic transistors on plastics and paper

The main advantage of organic electronics over the more widespread inorganic counterparts lies not in the electrical performance, but rather in the solution processability that opens up for low-cost flexible electronics (e.g. displays, sensors and smart tags) fabricated by using printing techniques. Replacing the commonly used laboratory-scale fabrication techniques with mass-printing techniques is, however, truly challenging, especially when low-voltage operation is required. In this thesis it is, nevertheless, demonstrated that low-voltage organic transistors can be fully printed with a similar performance to that of transistors made by laboratory scale techniques. The use of an ion-modulated type of organic field effect transistor (OFET) not only enabled low-voltage operation and printability, but was also found to result in low sensitivity to the surface roughness of the substrate. This allows not only the use of low-cost plastic substrates, but even the use of paper as a substrate. However, while absorption into the porous paper surface is advantageous in a graphical printing process, by reducing the spreading and the coffee-stain effect and by improving the adhesion, it provides great challenges when applying thin electrically active layers. In spite of these difficulties we were able to demonstrate the first low-voltage OFET to be fabricated on paper. We have also shown that low-cost incandescent lamps can be used for sintering printed metal-nanoparticles, and that the process was especially suitable on paper and compatible with a roll-to-roll manufacturing process.