Peptidase inhibitor 16 identifies a human regulatory T-cell subset with reduced FOXP3 expression over the first year of recent onset type 1 diabetes.

CD4+ T-cell subsets play a major role in the host response to infection, and a healthy immune system requires a fine balance between reactivity and tolerance. This balance is in part maintained by regulatory T cells (Treg), which promote tolerance, and loss of immune tolerance contributes to autoimmunity. As the T cells which drive immunity are diverse, identifying and understanding how these subsets function requires specific biomarkers. From a human CD4 Tconv/Treg cell genome wide analysis we identified peptidase inhibitor 16 (PI16) as a CD4 subset biomarker and we now show detailed analysis of its distribution, phenotype and links to Treg function in type 1 diabetes. To determine the clinical relevance of Pi16 Treg, we analysed PI16+ Treg cells from type 1 diabetes patient samples. We observed that FOXP3 expression levels declined with disease progression, suggesting loss of functional fitness in these Treg cells in Type 1 diabetes, and in particular the rate of loss of FOXP3 expression was greatest in the PI16+ve Treg. We propose that PI16 has utility as a biomarker of functional human Treg subsets and may be useful for tracking loss of immune function in vivo. The ability to stratify at risk patients so that tailored interventions can be applied would open the door to personalised medicine for Type 1 diabetes.

Corrosion resistance and in vitro response of laser-deposited Ti-Nb-Zr-Ta alloys for orthopedic implant applications.

While direct metal deposition of metallic powders, via laser deposition, to form near-net shape orthopedic implants is an upcoming and highly promising technology, the corrosion resistance and biocompatibility of such novel metallic biomaterials is relatively unknown and warrants careful investigation. This article presents the results of some initial studies on the corrosion resistance and in vitro response of laser-deposited Ti-Nb-Zr-Ta alloys. These new generation beta titanium alloys are promising due to their low elastic modulus as well as due the fact that they comprise of completely biocompatible alloying elements. The results indicate that the corrosion resistance of these laser-deposited alloys is comparable and in some cases even better than the currently used commercially-pure (CP) titanium (Grade 2) and Ti-6Al-4V ELI alloys. The in vitro studies indicate that the Ti-Nb-Zr-Ta alloys exhibit comparable cell proliferation but enhanced cell differentiation properties as compared with Ti-6Al-4V ELI.

Bioactivity and mineralization of hydroxyapatite with bioglass as sintering aid and bioceramics with Na3Ca6(PO4)5 and Ca5(PO4)2SiO4 in a silicate matrix.

Hydroxyapatite and Bioglass®-45S5 were sintered together creating new ceramic compositions that yielded increased apatite deposition and osteoblast differentiation and proliferation in vitro compared to hydroxyapatite. The sintered products characterized by X-ray diffraction, revealed hydroxyapatite as the main phase when small quantities (1, 2.5 and 5wt.%) of bioglass was added. Bioglass behaved as a sintering aid with ß-TCP (Ca3(PO4)2) being the minor phase. The amount of ß-TCP increased with the amount of bioglass added. In compositions with larger additions of bioglass (10 and 25wt.%), new phases with compositions of calcium phosphate silicate (Ca5(PO4)2SiO4) and sodium calcium phosphate (Na3Ca6(PO4)5) were formed respectively within amorphous silicate matrices. In vitro cell culture studies of the ceramic compositions were examined using bone marrow stromal cell (BMSC). Cell proliferation and differentiation of bone marrow stromal cells into osteoblasts were determined by Pico Green DNA assays and alkaline phosphatase (ALP) activity, respectively. All hydroxyapatite-bioglass co-sintered ceramics exhibited larger cell proliferation compared to pure hydroxyapatite samples. After 6days in cell culture, the ceramic with Ca5(PO4)3SiO4 in a silicate matrix formed by reacting hydroxyapatite with 10wt.% bioglass exhibited the maximum proliferation of the BMSC's. The ALP activity was found to be largest in the ceramic with Na3Ca6(PO4)5 embedded in a silicate matrix synthesized by reacting hydroxyapatite with 25wt.% bioglass.

Reproducibility of intravascular ultrasound virtual histology analysis.

OBJECTIVE: Intravascular ultrasound with virtual histology analysis (IVUS-VH) is a novel technology which allows for the identification of discrete atherosclerotic plaque components using radiofrequency backscatter data. Whether the composition of these plaques can be monitored accurately in a longitudinal fashion remains unclear. We sought to evaluate the reproducibility of plaque composition measurements as determined by IVUS-VH in a clinical setting. METHODS: Sixteen consecutive patients who underwent percutaneous coronary intervention were included in this study. Prior to and then again following intervention, IVUS images with VH processing were obtained with motorized pullback. Up to 4 frames were selected for analysis for each patient, with a total of 24 IVUS frames used. An IVUS frame was chosen with visible angiographic and ultrasound landmarks. The matching frame on the second pullback was identified using these landmarks. For each frame, vessel and lumen area as well as plaque composition by VH were determined. RESULTS: There was a high level of agreement between the two pullback measurements for lumen area, vessel area, and plaque burden (the Spearman rank-order correlation coefficients were 0.96, 0.96, and 0.95, respectively). Similarly, for plaque components by VH, the coefficients ranged from .90 to .97 and 0.84 to 0.92 for segmental volumetric analysis. The Bland-Altman plots indicated proportional error for the differences of the four measurements between the two pullback trials and were associated with high coefficients of reproducibility. CONCLUSIONS: Discrete measurements of plaque compositional area and volume in the clinical setting appear to have reproducibility comparable to that of traditional IVUS measurements.

A review of materials, fabrication methods, and strategies used to enhance bone regeneration in engineered bone tissues.

Over the last decade, bone engineered tissues have been developed as alternatives to autografts and allografts to repair and reconstruct bone defects. This article provides a review of the current technologies in bone tissue engineering. Factors used for fabrication of three-dimensional bone scaffolds such as materials, cells, and biomolecular signals, as well as required properties for ideal bone scaffolds, are reviewed. In addition, current fabrication techniques including rapid prototyping are elaborated upon. Finally, this review article further discusses some effective strategies to enhance cell ingrowth in bone engineered tissues; for example, nanotopography, biomimetic materials, embedded growth factors, mineralization, and bioreactors. In doing so, it suggests that there is a possibility to develop bone substitutes that can repair bone defects and promote new bone formation for orthopedic applications.