The endometrium is receptive to the embryo during a restricted window in the mid-secretory phase. My objectives were to develop a minimally-invasive endometrial sampling method for gene expression profiling, and to identify genes differentially expressed in the receptive phase. Twenty-three normo-ovulatory women underwent uterine fluid aspiration during the pre-receptive (LH+2) and receptive (LH+7) phase of the same natural cycle. RNA was extracted, reverse transcribed, amplified and hybridized to whole-genome microarrays. Unsupervised hierarchical clustering revealed self-segregation of pre-receptive and receptive samples. Importantly, profiling by uterine fluid aspiration was representative of biopsy. An unpaired t-test with a false discovery rate of 0.05 and a Δ threshold of 4-fold identified 245 unique transcripts as differentially expressed in the receptive phase. NanoString analysis validated 96% of these genes. This approach will now allow us to correlate expression of these candidate biomarkers to implantation outcomes, towards the development of clinical assays predictive for endometrial receptivity.

Long-term applicability of current surgical interventions for the repair of articular cartilage is jeopardized by the formation of mechanically inferior repair tissue. Cartilage tissue engineering offers the possibility of developing functional repair tissue, similar to that of native cartilage, enabling long-lasting repair of cartilage defects. Current techniques, however, rely on the need for a large number of cells, requiring substantial harvesting of donor tissue or a separate cell expansion phase. As routine cell expansion methods tend to elicit negative effects on cell function, the following study describes an approach to generate large-sized engineered cartilage constructs (≥ 3 cm2) directly from a small number of immature rabbit chondrocytes (approximately 20,000), without the use of a scaffold. After characterizing the hyaline-like engineered constructs, the in vivo repair capacity was assessed in a chondral defect model in the patellar groove of rabbits. In vitro remodeling of the constructs developed in the bioreactor occurred as early as 3 weeks, with the histological staining exhibiting zonal differences throughout the depth of the tissue. With culturing parameters optimized (3 weeks growth under 15 mM NaHCO3), constructs were grown and implanted into critical-sized 4 mm chondral defects. Assessed after 1, 3 and 6 months (n=6), implants were scored macroscopically to evaluate integration and survival of the implants. Out of 18 rabbits, 16 received normal or nearly normal over-all repair assessment. Histological and immunohistochemical evaluation showed good integration with surrounding cartilage and underlying subchondral bone. Architectural remodeling of the constructs was present at each time point, with the presence of flattened chondrocytes at the implant surface and columnar arrangement of chondrocytes in deeper zones. The observation of in vivo remodeling was also supported by the changes in biochemical composition of the constructs. At each time point, constructs had a collagen to proteoglycan ratio similar to that of native cartilage (3:1 collagen to proteoglycan). In contrast, the repair tissue for each control group was inferior to that produced with treated defects. These initial results hold promise for the generation of engineered articular cartilage for the clinical repair of cartilage defects without the limitations of current surgical repair strategies. / Thesis (Master, Chemical Engineering) -- Queen's University, 2012-01-31 01:03:15.276

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Doctor of Philosophy(PhD) / Biomedical materials are being extensively researched, and many different types such as metals, metal alloys, and polymers are being used. Currently used biomedical materials are not perfect in terms of corrosion resistance, biocompatibility, and surface properties. It is not easy to fabricate from scratch new materials that can fulfill all requirements and an alternative approach is to modify the surface properties of current materials to cater to the requirements. Plasma immersion ion implantation (PIII) is an effective and economical surface treatment technique and that can be used to enhance the surface properties of biomaterials. The unique advantage of plasma modification is that the surface properties and functionalities can be enhanced selectively while the favorable bulk attributes of the materials such as strength remain unchanged. In addition, the non-line of sight feature of PIII is appropriate for biomedical devices with complex geometries such as orthopedic implants. However, care must be exercised during the plasma treatment because low-temperature treatment is necessary for heat-sensitive materials such as polymers which typically have a low melting point and glass transition temperature. Two kinds of biomedical materials will be discussed in this thesis. One is nickel titanium (NiTi) alloy which is a promising orthopedic implant material due to its unique shape memory and superelastic properties. However, harmful ions may diffuse from the surface causing safety hazards. In this study, we investigate the properties and performance of NiTi after nitrogen and oxygen PIII in terms of the chemical composition, corrosion resistance, and biocompatibility. The XPS results show that barrier layers mainly containing TiN and TiOx are produced after nitrogen and oxygen PIII, respectively. Based on the simulated in vitro and electrochemical corrosion tests, greatly reduced ion leaching and improved corrosion resistance are accomplished by PIII. Porous NiTi is also studied because the porous structure possesses better bone ingrowth capability and compatible elastic modulus with human bones. These advantages promote better recovery in patients. However, higher risks of Ni leaching are expected due to the increased exposed surface area and rougher topography than dense and smooth finished NiTi. We successfully apply PIII to porous NiTi and in vitro tests confirm good cytocompatibility of the materials. The other type of biomedical materials studied here is ultra-high molecular weight polyethylene (UHMWPE) which is a potential material for use in immunoassay plates and biosensors. In these applications, active antibodies or enzymes attached to a surface to detect molecules of interests by means of specific interactions are required. Moreover, the retention of enzyme activity is crucial in these applications. Therefore, the aim of this study is to investigate the use of PIII to prepare UHMWPE surfaces for binding of active proteins in terms of the binding density and ‘shelf life’ of the treated surfaces. Argon and nitrogen PIII treatments are attempted to modify the surface of UHMWPE. Horseradish peroxidase (HRP) is selected to conduct the protein binding test since it is a convenient protein to assay. Experimental results show that both PIII treated surfaces significantly improve the density of active HRP bound to the surface after incubation in buffer containing HRP. Furthermore, the PIII treated surfaces are found to perform better than a commercially available protein binding surface and the shelf life of the PIII treated surfaces under ambient conditions is at least six months. In conclusion, a biocompatible barrier layer on NiTi and a protein binding surface on UHMWPE is synthesized by PIII. The surface properties such as corrosion resistance and functionality on these two different types of substrates are improved by PIII.

Thesis (Ph.D.)--McMaster University (Canada), 1991. / Source: Dissertation Abstracts International, Volume: 53-01, Section: B, page: 0367.

Diss. (sammanfattning) Linköping : Univ., 2001. / Härtill 4 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2003. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of North Texas, Dec., 2007. / Title from title page display. Includes bibliographical references.