Repair of segmental bone defects with fiber-reinforced composite: a study of material development and an animal model on rabbits

The Repair of segmental defects in load-bearing long bones is a challenging task because of the diversity of the load affecting the area; axial, bending, shearing and torsional forces all come together to test the stability/integrity of the bone. The natural biomechanical requirements for bone restorative materials include strength to withstand heavy loads, and adaptivity to conform into a biological environment without disturbing or damaging it. Fiber-reinforced composite (FRC) materials have shown promise, as metals and ceramics have been too rigid, and polymers alone are lacking in strength which is needed for restoration. The versatility of the fiber-reinforced composites also allows tailoring of the composite to meet the multitude of bone properties in the skeleton. The attachment and incorporation of a bone substitute to bone has been advanced by different surface modification methods. Most often this is achieved by the creation of surface texture, which allows bone growth, onto the substitute, creating a mechanical interlocking. Another method is to alter the chemical properties of the surface to create bonding with the bone – for example with a hydroxyapatite (HA) or a bioactive glass (BG) coating. A novel fiber-reinforced composite implant material with a porous surface was developed for bone substitution purposes in load-bearing applications. The material’s biomechanical properties were tailored with unidirectional fiber reinforcement to match the strength of cortical bone. To advance bone growth onto the material, an optimal surface porosity was created by a dissolution process, and an addition of bioactive glass to the material was explored. The effects of dissolution and orientation of the fiber reinforcement were also evaluated for bone-bonding purposes. The Biological response to the implant material was evaluated in a cell culture study to assure the safety of the materials combined. To test the material’s properties in a clinical setting, an animal model was used. A critical-size bone defect in a rabbit’s tibia was used to test the material in a load-bearing application, with short- and long-term follow-up, and a histological evaluation of the incorporation to the host bone. The biomechanical results of the study showed that the material is durable and the tailoring of the properties can be reproduced reliably. The Biological response - ex vivo - to the created surface structure favours the attachment and growth of bone cells, with the additional benefit of bioactive glass appearing on the surface. No toxic reactions to possible agents leaching from the material could be detected in the cell culture study when compared to a nontoxic control material. The mechanical interlocking was enhanced - as expected - with the porosity, whereas the reinforcing fibers protruding from the surface of the implant gave additional strength when tested in a bone-bonding model. Animal experiments verified that the material is capable of withstanding load-bearing conditions in prolonged use without breaking of the material or creating stress shielding effects to the host bone. A Histological examination verified the enhanced incorporation to host bone with an abundance of bone growth onto and over the material. This was achieved with minimal tissue reactions to a foreign body. An FRC implant with surface porosity displays potential in the field of reconstructive surgery, especially regarding large bone defects with high demands on strength and shape retention in load-bearing areas or flat bones such as facial / cranial bones. The benefits of modifying the strength of the material and adjusting the surface properties with fiber reinforcement and bone-bonding additives to meet the requirements of different bone qualities are still to be fully discovered.

Role of Membrane Transporters, P-Glycoprotein and Mrp1, in The Placental Transfer of Drugs With Special Reference to Saquinavir and Quetiapine

Drug transporting membrane proteins are expressed in various human tissues and blood-tissue barriers, regulating the transfer of drugs, toxins and endogenous compounds into or out of the cells. Various in vitro and animal experiments suggest that P-glycoprotein (P-gp) forms a functional barrier between maternal and fetal blood circulation in the placenta thereby protecting the fetus from exposure to xenobiotics during pregnancy. The multidrug resistance-associated protein 1 (MRP1) is a relatively less studied transporter protein in the human placenta. The aim of this study series was to study the role of placental transporters, apical P-gp and basal MRP1, using saquinavir as a probe drug, and to study transfer of quetiapine and the role of P-gp in its transfer in the dually perfused human placenta/cotyledon. Furthermore, two ABCB1 (encoding P-gp) polymorphisms (c.3435C>T, p.Ile1145Ile and c.2677G>T/A, p.Ala893Ser/Thr) were studied to determine their impact on P-gp protein expression level and on the transfer of the study drugs. Also, the influence of the P-gp protein expression level on the transfer of the study drugs was addressed. Because P-gp and MRP1 are ATP-dependent drug-efflux pumps, it was studied whether exogenous ATP is needed for the function of ATP-dependent transporter in the present experimental model. The present results indicated that the addition of exogenous ATP was not necessary for transporter function in the perfused human placental cotyledon. Saquinavir and quetiapine were both found to cross the human placenta; transplacental transfer (TPTAUC %) for saquinavir was <0.5% and for quetiapine 3.7%. Pharmacologic blocking of P-gp led to disruption of the blood-placental barrier (BPB) and increased the placental transfer of P-gp substrate, saquinavir, into the fetal circulation by 6- to 8-fold. In reversed perfusions P-gp, MRP1 and possibly OATP2B1 had a negligible role in the fetal-to-maternal transfer of saquinavir. The TPTAUC % of saquinavir was about 100-fold greater from the fetal side to the maternal side compared with the maternal-to-fetal transfer. P-gp activity is not likely to modify the placental transfer of quetiapine. Higher P-gp protein expression levels were associated with the variant allele 3435T, but no correlation was found between the TPTAUC % of saquinavir and placental P-gp protein expression. The present results indicate that P-gp activity drastically affects the fetal exposure to saquinavir, and suggest that pharmacological blockade of the P-gp activity during pregnancy may pose an increased risk for adverse fetal outcome. The blockade of P-gp activity could be used in purpose to obtain higher drug concentration to the fetal side, for example, in prevention (to decrease virus transfer to fetal side) or in treating sick fetus.

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.

The evaluation of hazardous gas components caused by the thermal degradation of plant oils and animal fats

Neste Oil has introduced plant oils and animal fats for the production of NExBTL renewable diesel, and these raw materials differ from the conventional mineral based oils. One subject of new raw materials study is thermal degradation, or in another name pyrolysis, of these organic oils and fats. The aim of this master’s thesis is to increase knowledge on thermal degradation of these new raw materials, and to identify possible gaseous harmful thermal degradation compounds. Another aim is to de-termine the health and environmental hazards of identified compounds. One objective is also to examine the formation possibilities of hazardous compounds in the produc-tion of NExBTL-diesel. Plant oils and animal fats consist mostly of triglycerides. Pyrolysis of triglycerides is a complex phenomenon, and many degradation products can be formed. Based on the literature studies, 13 hazardous degradation products were identified, one of which was acrolein. This compound is very toxic and dangerous to the environment. Own pyrolysis experiments were carried out with rapeseed and palm oils, and with a mix-ture of palm oil and animal fat. At least 12 hazardous compounds, including acrolein, were analysed from the gas phase. According to the experiments, the factors which influence on acrolein formation are the time of the experiment, the sphere (air/hydrogen) in which the experiment is carried out, and the characteristics of the used oil. The production of NExBTL-diesel is not based on pyrolysis. This is why thermal degradation is possible only when abnormal process conditions prevail.

First international workshop for small animal arthroscopy : matkakertomus

Jarmo Rintasalo, Pentti Tapio

Sustainability - a challenge to animal production and breeding

Selostus: Kestävän kehityksen vaatimukset kotieläintuotannossa ja -jalostuksessa

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

Detection of bias in animal model pedigree indices of heifers

Selostus: Eläinmalliin perustuvien hiehojen odotusarvojen luotettavuus jalostusarvon ennusteena

Arrangement of experiments for simulating the effects of elevated temperatures and elevated CO2 levels on field-sown crops in Finland

Selostus: Koejärjestelyt kohonneen lämpötilan ja CO2-tason vaikutusten simuloimiseksi peltokasveilla Suomessa

Betaiinin tuotannon sivujakeiden mikrosuodattaminen teräskeraamisella kalvolla

Betaiini on ammoniumyhdiste, jota käytetään esimerkiksi eläinten rehussa, kosmetiikassa ja lääkkeissä. Danisco Animal Nutrition Finnfeeds Finland Oy:n Naantalin tehdas on maailman johtava betaiinin tuottaja ja raaka-aineena tehtaalla käytetään melassierotuksesta saatavaa betaiinimelassia. Kiteisen betaiinin puhdistusprosessin yhteydessä syntyybetaiinipitoisia sivujakeita, jotka sisältävät huomattavan määrän betaiinia, minkä takia niiden jatkokäsittely on tärkeää. Betaiinin tuotannon sivujakeet ovat erittäin vaikeasti suodattuvia orgaanisia liuoksia, joiden koostumuksia ei täysin tunneta. Tämän työn tarkoituksena oli puhdistaa betaiinin tuotannon sivujakeita mikrosuodattamalla niitä teräskeraamisella kalvolla. Työn kokeellisessa osassa suoritettiin suodatusparametrien eli pH:n, lämpötilan, TMP:n ja betaiiniliuoksen kuiva-ainepitoisuuden optimointi sekä konsentrointikokeita. Mikrosuodatus suoritettiin Graver Technologiesin Scepter-putkimoduulilla, joka toimi ohivirtausperiaatteella ja jonka huokoskoko oli 0,1 ¿m. Scepter-moduuli koostui ruostumattomasta teräksestä sintratuista putkimoduuleista, joissa erottavana kerroksena toimi TiO2. Esikokeiden perusteella todettiin ettei pH:lla ollut suurta vaikutusta suodatukseen. Permeaattivuo kasvoi selvästi lämpötilan ja TMP:nkasvaessa. Vuo taas huononi ja permeaatin sameus lisääntyi selvästi 35 % korkeammissa kuiva-ainepitoisuuksissa. Konsentrointikokeet suoritettiin betaiiniliuoksen refraktrometrisessa kuiva-ainepitoisuudessa, BetRk, 35 %, 80 °C lämpötilassa ja betaiiniliuoksen omassa pH:ssa (pH 8-9,5). Esikokeiden tulosten perusteella konsentrointikokeet suoritettiin TMP:ssa 0,6; 0,8 ja 1,0 bar. Betaiinin tuotannonsivujakeiden konsentrointikokeissa saannoksi saatiin 95 %. Suodatustuloksista havaittiin, että betaiinin tuotannon sivujakeen erä vaikutti voimakkaasti suodatuksen toimivuuteen. Konsentrointikokeissa suodatukset suoritettiin sekäuusilla mikrosuodatusmoduuleilla että vanhalla moduulilla, joka oli jo kulunut.Kulumisen ei kuitenkaan havaittu huonontavan suodatustehokkuutta. Konsentrointikokeiden perusteella voidaan laitteiston pesuväliksi arvioida noin viikko ja pesu tulisi suorittaa sekä emäksisellä että happamalla pesuaineella.

The Rein-Deer Drawn from the living Animal

Stockton 1789