Fabrication of bioactive novel scaffold by solid-state reaction sintering for bone regeneration.

In this work we present a new type of scaffold obtained by solid-state reaction, simultaneous sintering of a mixture of precursor oxides, carbonates, and organic substances, the latter used for pore generation. Having variable local composition, exhibits excellent overall physicochemical and bioactivity response. Open porosity is about 50%-60% and its permeability 10-11  m2 . X-ray diffraction exhibits the presence of a sodium-calcium silicate and sodium-calcium phosphate crystalline phases. Additionally, by mechanical compression tests the range of failure stress obtained for the scaffolds was 0.3-1.1 MPa. The bioactivity and dissolution rate of the scaffolds were evaluated by in vitro tests. After 1 week soaking in simulated body fluid, the formation of a continuous hydroxyapatite layer, which does not differentiate local compositions, was observed. Our results from cell culture tests clearly indicate that during hydroxyapatite layer formation, scaffolds do not liberate any cytotoxic substances. Moreover, cells seeded in the hydroxyapatite-covered scaffolds grew better than the control.

High-throughput meta-analysis and validation of differentially expressed genes as potential biomarkers of ionizing radiation-response.

BACKGROUND AND PURPOSE: The high-throughput analysis of gene expression in ionizing radiation (IR)-exposed human peripheral white blood cells (WBC) has emerged as a novel method for biodosimetry markers detection. We aimed to detect IR-exposure differential expressed genes (DEGs) as potential predictive biomarkers for biodosimetry and radioinduced-response. MATERIALS AND METHODS: We performed a meta-analysis of raw data from public microarrays of ex vivo low linear energy transfer-irradiated human peripheral WBC. Functional enrichment and transcription factors (TF) detection from resulting DEGs were assessed. Six selected DEGs among studies were validated by qRT-PCR on mRNA from human peripheral blood samples from nine healthy human donors 24 h after ex vivo X-rays-irradiation. RESULTS: We identified 275 DEGs after IR-exposure (parameters: |lfc| ≥ 0.7, q value <0.05), enriched in processes such as regulation after IR-exposure, DNA damage checkpoint, signal transduction by p53 and mitotic cell cycle checkpoint. Among these DEGs, DRAM1, NUDT15, PCNA, PLK2 and TIGAR were selected for qRT-PCR validation. Their expression levels significantly increased at 1-4 Gy respect to non-irradiated controls. Particularly, PCNA increased dose dependently. Curiously, TCF4 (Entrez Gene: 6925), detected as overrepresented TF in the radioinduced DEGs set, significantly decreased post-irradiation. CONCLUSION: These six DEGs show potential to be proposed as candidates for IR-exposure biomarkers, considering their observed molecular radioinduced-response. Among them, TCF4, bioinformatically detected, was validated herein as an IR-responsive gene.