Based on these findings, PRP can be recommended for fast delivery of growth factors whereas A-PRF is better-suited for long-term release.

The aim of this study was to evaluate the effect of deproteinized bovine bone graft material on new bone formation in a guided bone regeneration model system. In 20 rabbits, a periosteal skin flap was raised uncovering the calvaria. A form stable hemispherical dome made of poly-lactic acid (PLA) was placed onto the roughened calvaria. Prior to placement, the dome was either filled with peripheral blood alone (control group, 8 rabbits), or with blood and OsteoGraf/N-300 (test group, 12 rabbits). The wound was closed for primary healing. Morphometric assessment of 1- and 2-month undecalcified histologic specimens revealed better tissue fill in the test domes at 1 month (test 99%, control 55%) (P < 0.05) and 2 months (t, 100%; c, 82%). The fraction of the new bone within the regenerated tissue was higher in the test specimens at 1 month (t, 22%; c, 12%) (P < 0.05) and 2 months (t, 34%; c, 24%). The fraction of the entire space underneath the domes occupied by bone was higher in the test at 1 month, but higher in the controls at 2 months. The fraction of the bone substitute material in contact with bone increased from 1 month (34% +/- 14) to 2 months (45% +/- 5). The surface fraction of osteoblast layers was tendentially higher in the test at 1 month but higher in the control specimens at 2 months. In both test and control, initially woven bone was formed which underwent subsequent remodeling. Cellular degradation of the deproteinized bone graft was frequently detected. It is concluded that deproteinized bovine bone mineral has osteoconductive properties and can initially accelerate new bone formation during guided bone regeneration by increased recruitment of osteoblasts.

The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in one-third of patients with de novo acute myeloid leukemia (AML). Mutated FLT3 variants are constitutively active kinases signaling via AKT kinase, MAP kinases, and STAT5. FLT3 inhibitors have been approved for the treatment of FLT3-mutated AML. However, treatment response to FLT3 inhibitors may be short-lived, and resistance may emerge. Compounds targeting STAT5 may enhance and prolong effects of FLT3 inhibitors in this subset of patients with FLT3-mutated AML. Here STAT5-inhibitor AC-4-130, FLT3 inhibitor midostaurin (PKC412), BMI-1 inhibitor PTC596, MEK-inhibitor trametinib, MCL1-inhibitor S63845, and BCL-2 inhibitor venetoclax were assessed as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells grown in the absence or presence of bone marrow stroma. Synergistic effects on cell viability were detected in both FLT3-mutated and FLT3-wild-type AML cells treated with AC-4-130 in combination with the MCL1 inhibitor S63845. AML patient samples with a strong response to AC-4-130 and S63845 combination treatment were characterized by mutated FLT3 or mutated TET2 genes. Susceptibility of AML cells to AC-4-130, PTC596, trametinib, PKC412, and venetoclax was altered in the presence of HS-5 stroma. Only the MCL1 inhibitor S63845 induced cell death with equal efficacy in the absence or presence of bone marrow stroma. The combination of the STAT5-inhibitor AC-4-130 and the MCL1 inhibitor S63845 may be an effective treatment targeting FLT3-mutated or TET2-mutated AML.