Fabrication and Characterization of Nanopillar-Like HA Coating on Porous Ti6Al4V Scaffold by a Combination of Alkali–Acid-Heat and Hydrothermal Treatments

Porous titanium scaffold with suitable porous architecture exhibits enormous potentials for bone defect repairs.However,insufficient osteointegration and osteoinduction still remain to open as one of the major problems to achieve satisfactory therapeutic effect.To solve this problem,many studies have been carried out to improve the bioactivity of porous titanium scaff old by surface modifications.In this study,porous Ti6Al4V scaff olds were fabricated using additive manufacturing technique.Porous architectures were built up based on a diamond pore structure unit.Alkali–acid-heat(AH)treatment was applied to create a TiO2 layer on the porous Ti6Al4V scaff old(AH-porous Ti6Al4V).Subsequently,a hydrothermal treatment was employed to enable the formation of HA coating with nanopillar-like morphology on the alkali–acid-heat-treated surface(HT/AH-porous Ti6Al4V).The effects of surface modifications on apatite-forming ability,protein adsorption,cell attachment,cell proliferation and osteogenic gene expression were studied using apatite-forming ability test,protein adsorption assay and in vitro cell culture assay.It was found that the HT/AH-porous Ti6Al4V exhibited the highest apatite formation ability and best affinity to fibronectin and vitronectin.In vitro studies indicated that the mesenchymal stem cells(MSCs)cultured on the HT/AH-porous Ti6Al4V presented improved adhesion and differentiation compared with the porous Ti6Al4V and AH-porous Ti6Al4V.

Haplotype of platelet receptor P2RY12 gene is associated with residual clopidogrel on-treatment platelet reactivity

Objective： To investigate a possible association between common variations of the P2RY12 and the residual clopidogrel on-treatment platelet reactivity after adjusting for the influence of CYP2C19 tested by thromboe- lastography （TEG）. Methods： One hundred and eighty patients with acute coronary syndrome （ACS） treated with clopJdogrel and aspJdn were included and platelet function was assessed by TEG. Five selected P2RY12 single nu- cleotide polymorphisms （SNPs; rs6798347, rs6787801, rs6801273, rs6785930, and rs2046934）, which cover the common variations in the P2RY12 gene and its regulatory regions, and three CYP2C19 SNPs （ 2, 3, 17） were geno- typed and possible haplotypes were analyzed. Results： The high on-treatment platelet reactivity （HTPR） prevalence defined by a platelet inhibition rate 〈30% by TEG in adenosine diphosphate （ADP）-channel was 69 （38.33%）. Six common haplotypes were inferred from four of the selected P2RY12 SNPs （denoted H0 to H5） according to the linkage disequilibrium R square （except for rs2046934）. Haplotype H1 showed a significantly lower incidence of HTPR than the reference haplotype （H0） in the total study population while haplotypes H1 and H2 showed significantly lower incidences of HTPR than H0 in the nonsmoker subgroup after adjusting for CYP2Clg effects and demographic characteristics. rs2046934 （T744C） did not show any significant association with HTPR. Conclusions： The combination of common P2RY12 variations including regulatory regions rather than rs2046934 （T744C） that related to pharmacodynamics of clopidogrel in patients with ACS was independently associated with residual on-clopidogrel platelet reactivity. This is apart from the established association of the CYP2C19. This association seemed more important in the subgroup defined by smoking.