Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Department of Orthopaedic Surgery, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Acta Biomater. 2022 Aug;148:345-354. doi: 10.1016/j.actbio.2022.06.013. Epub 2022 Jun 11.
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 layers in 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 SIGNIFICANCE: 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 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-2 in 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.
纤维细胞生长因子-2（FGF-2）-磷酸钙复合涂层的骨科和牙科植入物由于 FGF-2 的生物活性促进了真皮形成、骨形成和血管生成。增强复合涂层中 FGF-2 的生物活性对于其在骨科和牙科中的更广泛应用非常重要。本研究将低分子量肝素（LMWH）掺入 FGF-2-磷酸钙复合涂层中，并阐明了 LMWH 在体外对复合涂层中 FGF-2 生物活性的增强作用。在过饱和的磷酸钙溶液中，成功地在氧化锆上形成了 LMWH-FGF-2-磷酸钙复合层。复合层由连续的宏观均匀层和小于 500nm 大小的由无定形磷酸钙组成的颗粒组成。在过饱和的磷酸钙溶液中存在 FGF-2 的情况下，添加 LMWH 后，氧化锆上沉积的 Ca 和 P 量几乎保持不变。在过饱和的磷酸钙溶液中，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 的有丝分裂和内皮管形成活性，以及复合层中诱导成骨分化基因表达模式的 FGF-2 活性。我们的结果表明，LMWH-FGF-2-磷酸钙复合层中 FGF-2 的增强的生物活性归因于 LMWH 介导的 FGF-2 量的增加，这维持了其在过饱和的磷酸钙溶液和复合层中的生物活性。LMWH-FGF-2-磷酸钙复合层是一种有前途的骨科和牙科植入物涂层。
涂层有纤维细胞生长因子-2（FGF-2）-磷酸钙复合层的骨科和牙科植入物由于 FGF-2 的生物活性而促进了真皮形成、骨形成和血管生成。增强 FGF-2 在这些层中的生物活性对于其在骨科和牙科中的更广泛应用非常重要。本研究证明了低分子量肝素（LMWH）在 LMWH-FGF-2-磷酸钙复合层中对 FGF-2 体外生物活性的增强作用。我们的结果表明，复合层中 FGF-2 的增强的生物活性源于 LMWH 介导的 FGF-2 量的增加，该量维持了其在 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的生物活性。
