Use of fiber-reinforced composite framework and thermochromic pigment in maxillofacial prostheses

The purpose of this investigation was to evaluate the possibility to enhance certain qualities of facial prostheses. Polymethyl methacrylate is still being used as base mate¬rial or clip carrier material, but it is hard and heavy, and debonding of the silicone from the acrylic base material is a frequent problem. This thesis aims to evaluate the use of fiber-reinforced composite (FRC) as framework material for maxillofacial silicone prostheses. FRC has been used as reinforcement in removable and fixed partial dentures since the 1990s. This material is lightweight and can be fabricated to compress the margins of the prosthesis slightly, to keep it tightly against the skin during jaw movements and facial expressions. Additionally, the use of a thermochromic pigment, colorless in room temperature and red in a cold environment, was studied in order to evaluate the possibility of using this color changing pigment in facial prostheses to mimic the color change of facial skin in cold weather. The tensile bond strength between pre-impregnated, unidirectional FRC and maxillofacial silicone elastomer was studied. Three different bonding agents or primers were compared. Bond strength was improved by one of the primers and by roughening the surface. The effect of a skin compressing glass fiber-reinforced composite framework on facial skin blood flow was studied by using a face mask, constructed with a compression pad corresponding to the outer margin of a glass fiber-reinforced framework beam of a facial prosthesis. The skin blood flow of ten healthy volunteers, aged 23-25 years, was measured during touch, light, and moderate compression of the skin, by using laser Doppler imaging technique. None of the compressions showed any marked effects on local skin blood flow. There were no significant differences between blood flow during compression and at baseline. Maxillofacial silicone elastomer was colored intrinsically with conventional color pigments: a control group containing only conventional pigments was compared to two test groups with 0.2 wt% and 0.6 wt% thermochromic pigment added. The color of the material was measured with a spectrophotometer in room temperature and after storage in a freezer. The color stability of the maxillofacial silicone elastomer colored with thermo¬chromic pigment was evaluated by artificial aging. The color dif¬ference of the L* (lightness) and a* values (redness), comparing color after the samples were stored at room temperature and in a freezer (-19°C), was statistically significant for both 0.2 wt% and 0.6 wt% thermo¬chromic pigment groups. The differences in the b* values (yellowness) were statistically significant for the 0.6 wt% group. Exposure to ultraviolet (UV) radiation led to visually noticeable and statistically signifi¬cant color changes (ΔE) in all color values in both test groups. The specimens containing thermochromic pigment were very sensitive to UV radiation. In conclusion, a framework of fiber-reinforced composite can successfully be bonded to maxillofacial silicone elastomer, and a framework beam, compressing the facial skin, did not remarkably alter the skin blood flow on healthy, young adults. The thermochromic pigment showed color change in maxillofacial silicone elastomer. However, artificial aging showed that it was too sensitive to UV radiation to be used, as such, in maxillofacial prostheses.

Prodrug strategies of antiviral nucleotides: Studies on enzymatically and thermally removable phosphate protecting groups

Antiviral nucleosides are compounds that are used against viruses, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV). To act as therapeutic agent, the antiviral nucleoside needs to be phosphorylated to nucleotide in the body in three consecutive phosphorylation steps by cellular or viral enzymes. The first phosphorylation to the nucleoside monophosphate is often inefficient and leads to poor antiviral activity. The antiviral efficacy can be improved by applying a prodrug strategy and delivering the antiviral nucleoside directly as its monophosphate. In prodrug strategies of antiviral nucleotides, the negative charges on the phosphate moiety are temporarily masked with protecting groups. Once inside the cell, the protecting groups are removed by enzymatic or chemical processes. Many prodrug strategies apply biodegradable protecting groups, the removal of which is triggered by esterase enzymes. Several studies have, however, demonstrated that the removal rate of the second and subsequent esterase labile protecting groups significantly slows down after the first protecting group is removed due to the negative charge on the phosphodiester intermediate, which disturbs the catalytic site of the enzyme. In this thesis, esterase labile protecting group strategies where the issue of retardation could be avoided were studied. Prodrug candidates of antiviral nucleotides were synthesized and kinetic studies on the chemical and enzymatic stability were carried out. In the synthesized compounds, the second protecting group is cleaved from the monophosphate some other mechanism than esterase triggered activation or the structure of prodrug requires only one protecting group. In addition, esterase labile protecting group which is additionally thermally removable was studied. This protecting group was cleaved from oligomeric phosphodiesters both enzymatically and thermally and seems most attractive of the studied phosphate protecting groups. However, the rate of the thermal removal still is too slow to allow efficient protection of longer oligonucleotides and needs optimization. Key words: antiviral, nucleotide, prodrug, protecting group, biodegradable

Fiber-reinforced composite fixed dental prostheses: Studies of the materials used as pontics

Fiber-reinforced composite fixed dental prostheses – Studies of the materials used as pontics University of Turku, Faculty of Medicine, Institute of Dentistry, Department of Biomaterials Science, Finnish Doctoral Program in Oral Sciences – FINDOS, Annales Universitatis Turkuensis, Turku, Finland 2015 Fiber-reinforced composites (FRC), a non-metallic biomaterial, represent a suitable alternative in prosthetic dentistry when used as a component of fixed dental prostheses (FDPs). Some drawbacks have been identified in the clinical performance of FRC restorations, such as delamination of the veneering material and fracture of the pontic. Therefore, the current series of studies were performed to investigate the possibilities of enhancing the mechanical and physical properties of FRC FDPs by improving the materials used as pontics, to then heighten their longevity. Four experiments showed the importance of the pontic design and surface treatment in the performance of FRC FDPs. In the first, the load-bearing capacities of inlay-retained FRC FDPs with pontics of various materials and thicknesses were evaluated. Three different pontic materials were assessed with different FRC framework vertical positioning. Thicker pontics showed increased load-bearing capacities, especially ceramic pontics. A second study was completed investigating the influence of the chemical conditioning of the ridge-lap surface of acrylic resin denture teeth on their bonding to a composite resin. Increased shear bond strength demonstrated the positive influence of the pretreatment of the acrylic surfaces, indicating dissolution of the denture surfaces, and suggesting potential penetration of the monomer systems into the surface of denture teeth. A third study analyzed the penetration depth of different monomer systems on the acrylic resin denture teeth surfaces. The possibility of establishing a durable bond between acrylic pontics and FRC frameworks was demonstrated by the ability of monomers to penetrate the surface of acrylic resin denture teeth, measured by a confocal scanning type microscope. A fourth study was designed to evaluate the load-bearing capacities of FRC FDPs using the findings of the previous three studies. In this case, the performance of pre-shaped acrylic resin denture teeth used as pontics with different composite resins as filling materials was evaluated. The filling material influenced the load-bearing capacities, providing more durable FRC FDPs. It can be concluded that the mechanical and physical properties of FRC FDPs can be improved as has been shown in the development of this thesis. The improvements reported then might provide long lasting prosthetic solutions of this kind, positioning them as potentially permanent rehabilitation treatments. Key words: fiber-reinforced composite, fixed dental prostheses, inlay-retained bridges, adhesion, acrylic resin denture teeth, dental material.

The Influence of Certain Processing Factors on the Durability of Yttrium Stabilized Zirconia Used As Dental Biomaterial

In dentistry, yttrium partially stabilized zirconia (ZrO2) has become one of the most attractive ceramic materials for prosthetic applications. The aim of this series of studies was to evaluate whether certain treatments used in the manufacturing process, such as sintering time, color shading or heat treatment of zirconia affect the material properties. Another aim was to evaluate the load-bearing capacity and marginal fit of manually copy-milled custom-made versus prefabricated commercially available zirconia implant abutments. Mechanical properties such as flexural strength and surface microhardness were determined for green-stage milled and sintered yttrium partially stabilized zirconia after different sintering time, coloring process and heat treatments. Scanning electron microscope (SEM) was used for analyzing the possible changes in surface structure of zirconia material after reduced sintering time, coloring and heat treatments. Possible phase change from the tetragonal to the monoclinic phase was evaluated by X-ray diffraction analysis (XRD). The load-bearing capacity of different implant abutments was measured and the fit between abutment and implant replica was examined with SEM. The results of these studies showed that the shorter sintering time or the thermocycling did not affect the strength or surface microhardness of zirconia. Coloring of zirconia decreased strength compared to un-colored control zirconia, and some of the colored zirconia specimens also showed a decrease in surface microhardness. Coloring also affected the dimensions of zirconia. Significantly decreased shrinkage was found for colored zirconia specimens during sintering. Heat treatment of zirconia did not seem to affect materials’ mechanical properties but when a thin coating of wash and glaze porcelain was fired on the tensile side of the disc the flexural strength decreased significantly. Furthermore, it was found that thermocycling increased the monoclinic phase on the surface of the zirconia. Color shading or heat treatment did not seem to affect phase transformation but small monoclinic peaks were detected on the surface of the heat treated specimens with a thin coating of wash and glaze porcelain on the opposite side. Custom-made zirconia abutments showed comparable load-bearing capacity to the prefabricated commercially available zirconia abutments. However, the fit of the custom-made abutments was less satisfactory than that of the commercially available abutments. These studies suggest that zirconia is a durable material and other treatments than color shading used in the manufacturing process of zirconia bulk material does not affect the material’s strength. The decrease in strength and dimensional changes after color shading needs to be taken into account when fabricating zirconia substructures for fixed dental prostheses. Manually copy-milled custom-made abutments have acceptable load-bearing capacity but the marginal accuracy has to be evaluated carefully.

Puristussylinterien valmistuksen kehittäminen

Tässä diplomityössä kehitettiin yksitoimisten puristussylinterien valmistusta Rautessa. Sylinterien valmistuksessa haastavin vaihe on sylinteriputken ja pohjan välinen hitsaus. Hitsauksen avuksi suunniteltiin sylinterin sisäpuolinen juuritukilaite. Hitsauskokeita suoritettiin hitsin pohjan jauhekaarihitsaukselle ja MAG-hitsaukselle. Juuritukilaitteen toimivuutta testattiin koehitsauksilla. Puristussylinterien materiaali on S355J2-terästä, jonka ainevahvuus on 20 – 60 mm. Paksujen rakenneterästen hitsauksessa täytyy ottaa huomioon hitsausliitoksen mekaanisten ominaisuuksien muuttuminen sekä eri halkeamien synty. Hitsauksen laatuun ja laadunhallintaan voidaan vaikuttaa monien eri tekijöiden avulla. Hitsausohjeen avulla, ja muut laatutekijät huomioiden, voidaan hitseille asetetut laatukriteerit täyttää. Juurituen käyttö nopeuttaa puristussylinterien hitsausta vähintään 50 %. Jauhekaarihitsaus kuparista juuritukea vasten synnyttää vaikeasti poistettavan kuonan juuren puolelle. Perinteinen MAG-hitsaus kuparista juuritukea vasten sisältää liian monta muuttujaa, mikä tekee siitä epäluotettavan pohjapalon hitsaukseen. Työssä suunnitellun juuritukilaitteen käyttö tuotannossa vaatii lisää hitsauskokeita.

Synthesis of Short Oligonucleotides on a Soluble Support by the Phosphoramidite Method

In the last decades, the chemical synthesis of short oligonucleotides has become an important aspect of study due to the discovery of new functions for nucleic acids such as antisense oligonucleotides (ASOs), aptamers, DNAzymes, microRNA (miRNA) and small interfering RNA (siRNA). The applications in modern therapies and fundamental medicine on the treatment of different cancer diseases, viral infections and genetic disorders has established the necessity to develop scalable methods for their cheaper and easier industrial manufacture. While small scale solid-phase oligonucleotide synthesis is the method of choice in the field, various challenges still remain associated with the production of short DNA and RNA-oligomers in very large quantities. On the other hand, solution phase synthesis of oligonucleotides offers a more predictable scaling-up of the synthesis and is amenable to standard industrial manufacture techniques. In the present thesis, various protocols for the synthesis of short DNA and RNA oligomers have been studied on a peracetylated and methylated β-cyclodextrin, and also on a pentaerythritol-derived support. On using the peracetylated and methylated β-cyclodextrin soluble supports, the coupling cycle was simplified by replacement of the typical 5′-O-(4,4′-dimethoxytrityl) protecting group with an acid-labile acetal-protected 5′-O-(1-methoxy-1-methylethyl) group, which upon acid-catalyzed methanolysis released easily removable volatile products. For this reason monomeric building blocks 5′-O-(1-methoxy-1-methylethyl) 3′-(2-cyano-ethyl-N,N-diisopropylphosphoramidite) were synthesized. Alternatively, on using the precipitative pentaerythritol support, novel 2´-O-(2-cyanoethyl)-5´-O-(1-methoxy-1-methylethyl) protected phosphoramidite building blocks for RNA synthesis have been prepared and their applicability by the synthesis of a pentamer was demonstrated. Similarly, a method for the preparation of short RNAs from commercially available 5´-O-(4,4´-dimethoxytrityl)-2´-O-(tert-butyldimethyl-silyl)ribonucleoside 3´-(2-cyanoethyl-N,N-diisopropylphosphoramidite) building blocks has been developed

Sähkötoimisten käsiproteesien nykyteknologian taso

Työssä selvitettiin sähkötoimisten käsiproteesien nykyteknologian taso. Selvitettäviä asioita olivat keskushermoston ja proteesin välisen hermokytkennän toteutustapa, sähkötoimisten käsiproteesien keskeiset tekniset ominaisuudet sekä käsiproteesin mekaaniset toteutustavat. Tutkimus suoritettiin kirjallisuustutkimuksena. Työhön valittiin esimerkkejä kaupallisesti saatavilla olevista käsiproteeseista jotka löytyivät internetistä hakemalla kaikkein edisty-neintä käsiproteesia. Työstä rajattiin pois proteesin suora kytkeminen keskushermostoon. Liikeinformaation välitys aivoilta proteesille onnistuu mittaamalla lihassähkökäyrä erilaisilla ihon ja lihasten päälle, ihon alle lihaksien yhteyteen tai suoraan hermojen yhteyteen asete-tuilla elektrodeilla. Lihassähkökäyrän mittaamisessa ihon pinnalta on ongelmana sähkömag-neettinen säteily, hiki, joka muuttaa ihon impedanssia ja elektrodien meneminen pois paikal-taan. Ihon alle asetettavat elektrodit kapseloituvat, mikä heikentää niiden toimintaa ja nii-den ihon läpi kulkevat johdot voivat altistaa kohdan infektioille tai takertua johonkin. Her-moihin suorassa kosketuksissa olevat elektrodit aiheuttavat lisäksi hermopinteen. Kohden-netulla uudelleenhermotuksella voidaan hermosyyt johtaa lihaksiin, jolloin lihaksista saa-daan biologiset vahvistimet lihassähkökäyrää varten tai korvaavalle ihoalueelle, johon koh-distuva kosketus tuottaa tuntemuksen käteen kohdistuvasta kosketuksesta. Käden menet-tämisen myötä menetettävät hermo-ohjaustiedot voivat osittain korvautua aivojen mukau-tuvuuden ansiosta, mikä mahdollistaa tekokäden käyttämisen oppimisen samalla tavoin kuin polkupyörällä ajon. Hermotakaisinkytkentä mahdollistaa proteesin paremman hallin-nan. On mahdollista valmistaa keinoihoa johon kohdistuva paine saa aikaan muutoksen sen sähköisissä ominaisuuksissa, mitä voidaan sitten käyttää varsinaisen hermoärsytyksen luo-van laitteen, kuten tynkää ärsyttävän täryttimen, ohjaamisessa. On mahdollista valmistaa keinolihaksia joiden avulla nivelten liike voidaan toteuttaa luonnollisen kaltaisilla rakenteilla ja jotka ovat jopa kymmeniä kertoja voimakkaampia kuin aidot lihakset. Nykyteknologian avulla on mahdollista rakentaa käsiproteesi joka liikeradoiltaan, voimal-taan ja hermotakaisinkytkennän osalta vastaa lähes täydellisesti aitoa ihmiskättä. Haasteena on vielä kokeiluasteella oleva teknologian taso sekä korkea hinta.