Bor İçeren Nano Hidroksiapatit Kompozitlerin Kemik Hücrelerindeki Moleküler Etki Mekanizmasının Araştırılması

Abstract

The structure of the bone and the self-renewal capacity are damaged by metabolic diseases and damages. The trace elements and hydroxyapatite crystals in the bone are important in the development of biomaterials to support the renewal of the extracellular matrix. In this study, it was assumed the boron loaded nanometer sized hydroxyapatite was supposed to support the construction of extracellular matrix by controlled boron release in order to prevent toxic effect. In this context, boron release kinetics from nanometer sized hydroxyapatite were calculated by ICP-MS method and it was found that boron was released in large proportion within 1 hour and the release was continued at constant low dose. The effect of the boron containing nanometer sized hydroxyapatite composite on the proliferation of SaOS-2 osteoblasts and human bone marrow derived mesenchymal stem cells was evaluated by the WST-1 method and compared with the effects of nanohydroxyapatite and boric acid, it has been shown that do not alter the proliferation rate in osteoblasts and increase proliferation in mesenchymal stem cells at high doses. Boron containing nanohydroxyapatite composites have been shown to increase osteogenic differentiation of mesenchymal stem cells by increasing alkaline phosphatase activity, as compared to nanohydroxyapatite composite and boric acid. The molecular mechanism of effective dose of boron-containing hydroxyapatite has been assessed by transcriptomic analysis and shown to affect genes involved in Wnt, TGF-β and response to stress signaling pathways when compared to nano-hydroxyapatite composite and boric acid. Eventually, a safe osteoconductive dose range of boron-containing nano hydroxyapatite composites for local repair of bone injuries and the molecular effect profile in the effective dose was determined has been determined. Further studies require the validation of the regenerative therapeutic effect window.