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多功能化调节羟基磷灰石与双膦酸盐的表面相互作用:抗骨质疏松和抗氧化应激材料

Multifunctionalization Modulates Hydroxyapatite Surface Interaction with Bisphosphonate: Antiosteoporotic and Antioxidative Stress Materials.

作者信息

Forte Lucia, Sarda Stéphanie, Torricelli Paola, Combes Christèle, Brouillet Fabien, Marsan Olivier, Salamanna Francesca, Fini Milena, Boanini Elisa, Bigi Adriana

机构信息

Department of Chemistry "G. Ciamician", University of Bologna, via Selmi 2, 40126 Bologna, Italy.

CIRIMAT, Université de Toulouse, CNRS, Université Toulouse 3 - Paul Sabatier, Toulouse INP ENSIACET, 4 allée Emile Monso, 31030 Toulouse cedex 4, France.

出版信息

ACS Biomater Sci Eng. 2019 Jul 8;5(7):3429-3439. doi: 10.1021/acsbiomaterials.9b00795. Epub 2019 Jun 25.

DOI:10.1021/acsbiomaterials.9b00795
PMID:33405727
Abstract

Multifunctionalized biomaterials with enhanced bone antiresorptive properties were obtained through adsorption of a bisphosphonate, risedronate, on hydroxyapatite (HA) nanocrystals functionalized with zinc ions and polyethylenimine (PEI). Zn incorporation into the HA structure amounts to about 8 atom %, whereas the PEI content of the bifunctionalized material ZnHAPEIBP is about 5.9 wt %. The mechanism of adsorption and release of the bisphosphonate on ZnHAPEI is compared with that on ZnHA: risedronate adsorption isotherm on ZnHA is a Langmuir type, whereas the isotherm of adsorption on ZnHAPEI is better fitted with a Freundlich model and involved a higher amount of adsorbed risedronate. In vitro cell tests were carried out with a coculture model of osteoblasts and osteoclasts using a model simulating oxidative stress and consequent cellular senescence and osteoporosis by the addition of HO. The conditions utilized in the coculture model strongly affect osteoblast behavior. The results show that the composite materials allow an increase in osteoblast viability and recover impairment, revealing a novel characteristic of risedronate that is able to counteract the negative effects of oxidative stress when associated with differently functionalized samples. Both PEI and the bisphosphonate reduce osteoclast viability. Moreover, PEI, and even more risedronate, exerts an inhibitory effect on osteoclast activity.

摘要

通过将双膦酸盐利塞膦酸盐吸附在经锌离子和聚乙烯亚胺(PEI)功能化的羟基磷灰石(HA)纳米晶体上,获得了具有增强骨抗吸收性能的多功能生物材料。锌掺入HA结构中的量约为8原子%,而双功能化材料ZnHAPEIBP的PEI含量约为5.9 wt%。比较了双膦酸盐在ZnHAPEI上的吸附和释放机制与在ZnHA上的吸附和释放机制:利塞膦酸盐在ZnHA上的吸附等温线是朗缪尔型,而在ZnHAPEI上的吸附等温线更符合弗伦德里希模型,并且涉及更高量的吸附利塞膦酸盐。使用通过添加HO模拟氧化应激以及随之而来的细胞衰老和骨质疏松症的模型,对成骨细胞和破骨细胞的共培养模型进行了体外细胞测试。共培养模型中使用的条件强烈影响成骨细胞的行为。结果表明,复合材料可提高成骨细胞的活力并恢复损伤,揭示了利塞膦酸盐的一种新特性,即当与不同功能化的样品结合时能够抵消氧化应激的负面影响。PEI和双膦酸盐均降低破骨细胞的活力。此外,PEI,甚至更多的利塞膦酸盐,对破骨细胞活性具有抑制作用。

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