The enhancing effects of heparin on the biological activity of FGF-2 in heparin?FGF-2?calcium phosphate composite layers
The enhancing effects of heparin on the biological activity of FGF-2 in heparin?FGF-2?calcium phosphate composite layers
复制标题
肝素对肝素·FGF-2·磷酸钙复合层中FGF-2生物活性的增强作用
DOI：
10.1016/j.actbio.2022.06.013
复制
发表时间：
2022
影响因子：
9.7
通讯作者：
Ito Atsuo
中科院分区：
文献类型：
--
作者：
Yasunaga Mayu;Kobayashi Fumiko;Sogo Yu;Murotomi Kazutoshi;Hirose Motohiro;Hara Yuki;Yamazaki Masashi;Ito Atsuo
由于FGF-2的生物活性，涂覆有成纤维细胞生长因子-2（FGF-2）-磷酸钙复合层的骨科和牙科植入物促进真皮形成、骨形成和血管生成。增强复合材料层中FGF-2的生物活性对其在骨科和牙科中的广泛应用具有重要意义。本研究将低分子量肝素（LMWH）掺入FGF-2-磷酸钙复合层中，并阐明了LMWH对体外复合层中FGF-2生物活性的增强作用。在过饱和磷酸钙溶液中，LMWH-FGF-2-磷酸钙复合层成功地在氧化锆上形成。复合层包括连续和宏观上均匀的层和由无定形磷酸钙组成的尺寸小于500 nm的颗粒。在过饱和磷酸钙溶液中加入FGF-2后，加入LMWH后，氧化锆表面的Ca和P沉积量几乎不变。过饱和磷酸钙溶液中的LMWH增加了溶液中FGF-2的稳定性和复合层中FGF-2的量。复合层中的LMWH增加了FGF-2的促有丝分裂活性和内皮管形成活性，以及FGF-2诱导复合层中成骨分化基因表达模式的活性。我们的研究结果表明，LMWH-FGF-2-磷酸钙复合层中FGF-2的生物活性增强归因于LMWH介导的FGF-2量的增加，其在过饱和磷酸钙溶液和复合层中保持其生物活性。LMWH−FGF-2−磷酸钙复合层是骨科和牙科植入物的一种有前途的涂层。重要性声明由于FGF-2的生物活性，用成纤维细胞生长因子-2（FGF-2）−磷酸钙复合层涂覆的骨科和牙科植入物可促进真皮形成、骨形成和血管生成。提高成纤维细胞生长因子-2在蛋鸡体内的生物学活性，对扩大其在骨科和口腔医学中的应用具有重要意义。本研究证明了LMWH-FGF-2-磷酸钙复合层中含有的低分子量肝素（LMWH）对FGF-2体外生物活性的增强作用。我们的研究结果表明，复合层内FGF-2的生物活性增强源于LMWH介导的FGF-2量的增加，其在LMWH-FGF-2-磷酸钙复合层和用于涂覆复合层的过饱和磷酸钙溶液中保持其生物活性。
Orthopedic and dental implants coated with fibroblast growth factor-2 (FGF-2)−calcium phosphate composite layers promote dermis formation, bone formation, and angiogenesis because of the biological activity of FGF-2. Enhancing the biological activity of FGF-2 in the composite layers is important for its wider application in orthopedics and dentistry. This study incorporated low-molecular-weight heparin (LMWH) into the FGF-2−calcium phosphate composite layers and clarified the enhancing effects of LMWH on the biological activity of FGF-2 in the composite layersin vitro. LMWH−FGF-2−calcium phosphate composite layers were successfully formed on zirconia in supersaturated calcium phosphate solutions. The composite layers comprised continuous and macroscopically homogeneous layers and particles smaller than 500 nm in size composed of amorphous calcium phosphate. The amounts of Ca and P deposited on zirconia remained almost unchanged with the addition of LMWH under the presence of FGF-2 in the supersaturated calcium phosphate solution. The LMWH in the supersaturated calcium phosphate solution increased the stability of FGF-2 in the solution and the amount of FGF-2 in the composite layers. The LMWH in the composite layers increased the mitogenic and endothelial tube-forming activities of FGF-2, and FGF-2 activity of inducing osteogenic differentiation gene expression pattern in the composite layers. Our results indicate that the enhanced biological activity of FGF-2 in the LMWH−FGF-2−calcium phosphate composite layers is attributed to an LMWH-mediated increase in the amount of FGF-2, which maintains its biological activity in the supersaturated calcium phosphate solution and the composite layers. The LMWH−FGF-2−calcium phosphate composite layer is a promising coating for orthopedic and dental implants.Statement of significanceOrthopedic and dental implants coated with fibroblast growth factor-2 (FGF-2)−calcium phosphate composite layers promote dermis formation, bone formation, and angiogenesis because of the biological activity of FGF-2. Enhancing the biological activity of FGF-2 in the layers is important for wider its application in orthopedics and dentistry. This study demonstrates the enhancing effects of low-molecular-weight heparin (LMWH) contained within LMWH−FGF-2−calcium phosphate composite layers on the biological activity of FGF-2in vitro. Our results indicate that the enhanced biological activity of FGF-2 within the composite layers arises from an LMWH-mediated increase in the amount of FGF-2, which maintains its biological activity in the LMWH−FGF-2−calcium phosphate composite layers and supersaturated calcium phosphate solutions used for coating the composite layers.