Heparinization of Beta Tricalcium Phosphate: Osteo-immunomodulatory Effects
Heparinization of Beta Tricalcium Phosphate: Osteo-immunomodulatory Effects
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DOI：
10.1002/adhm.201700867
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发表时间：
2018-03-07
影响因子：
10
通讯作者：
Ginebra, Maria-Pau
中科院分区：
文献类型：
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作者：
Diez-Escudero, Anna;Espanol, Montserrat;Ginebra, Maria-Pau
免疫细胞在调节骨动力学方面发挥着至关重要的作用。这激发了人们对开发能够调节免疫和骨骼系统的生物材料的兴趣。在这项研究中，磷酸钙盘（即β-磷酸三钙，-TCP）用肝素功能化，以研究对免疫和干细胞反应的影响。结果表明，与非功能化的椎间盘相比，功能化的表面下调了人类单核细胞和中性粒细胞的过氧化氢和促炎细胞因子（肿瘤坏死因子α和白细胞介素1β）的释放。巨噬细胞在两种陶瓷基底上均显示出拉长和圆形形状，但肝素化-TCP上的细胞形态在72小时后趋向于更高的伸长。与-TCP和对照相比，肝素化底物支持大鼠间充质干细胞（MSC）粘附和增殖，并预测向成骨细胞谱系的分化。通过用巨噬细胞上清液培养 MSC 来评估炎症反应和成骨之间的耦合。与肝素化底物接触的炎症的下调诱导 MSC 表达更高的骨相关标志物。
Immune cells play a vital role in regulating bone dynamics. This has boosted the interest in developing biomaterials that can modulate both the immune and skeletal systems. In this study, calcium phosphates discs (i.e., beta-tricalcium phosphate, -TCP) are functionalized with heparin to investigate the effects on immune and stem cell responses. The results show that the functionalized surfaces downregulate the release of hydrogen peroxide and proinflammatory cytokines (tumor necrosis factor alpha and interleukin 1 beta) from human monocytes and neutrophils, compared to nonfunctionalized discs. The macrophages show both elongated and round shapes on the two ceramic substrates, but the morphology of cells on heparinized -TCP tends toward a higher elongation after 72 h. The heparinized substrates support rat mesenchymal stem cell (MSC) adhesion and proliferation, and anticipate the differentiation toward the osteoblastic lineage as compared to -TCP and control. The coupling between the inflammatory response and osteogenesis is assessed by culturing MSCs with the macrophage supernatants. The downregulation of inflammation in contact with the heparinized substrates induces higher expression of bone-related markers by MSCs.