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新型可吸收聚富马酸丙二醇酯/羟基磷灰石骨水泥的合成制备及体外生物活性研究
Synthesis and in vitro bioactivity study of a novel absorbable polypropylene fumarate/hydroxyapatite bone cement
投稿时间:2024-08-16  
DOI:10.3969/j.issn.1672-5972.2025.03.001
中文关键词:  聚富马酸丙二醇酯  羟基磷灰石  骨水泥  力学
英文关键词:Polypropylene fumarate  Hydroxyapatite  Bone cement  Mechanical properties
基金项目:新疆维吾尔自治区自然科学基金面上项目(2023D01C93);“天山英才”医药卫生高层次人才项目计划((TSYC202401A031);成都医学院第一附属医院科研项目(CYFY-GQ73
作者单位邮编
黄晓夏* 新疆医科大学研究生院新疆 乌鲁木齐830011
新疆军区总医院脊柱外科新疆 乌鲁木齐830099 
830099
王江华 新疆军区总医院药剂科新疆 乌鲁木齐830099 830099
陈家瀚 成都医学院第一附属医院骨科四川 成都610500 610500
马锐 新疆军区总医院脊柱外科新疆 乌鲁木齐830099 830099
刘涛 新疆军区总医院脊柱外科新疆 乌鲁木齐830099 830099
尹东锋* 新疆军区总医院药剂科新疆 乌鲁木齐830099 830099
滕勇* 新疆军区总医院脊柱外科新疆 乌鲁木齐830099 830099
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中文摘要:
      目的 探讨聚富马酸丙二醇酯(polypropylene fumarate, PPF)/羟基磷灰石(hydroxyapatite, HA)制备新型可吸收骨水泥的配方及其体外生物活性实验研究。方法 采用两步法制备PPF,并使用凝胶渗透色谱仪测定其数均分子量、重均分子量及聚合度分布指数,同时通过氢谱对PPF的结构进行分析。通过制备不同分子量的PPF(6 h、8 h)热交联体系、PPF(8 h)与DMPT按1∶1和1∶10比例的热交联体系、不同粒径的HA与PPF热交联体系,以及不同含量HA(10%、20%、30%)的热交联体系,考察其力学性能及体外生物相容性。结果 通过两步法已成功制备PPF,氮气保护和油泵可以减小分子量分布(polydispersity, PD)值、加快反应,但时间超过24 h,分子量反而下降。纳米羟基磷灰石投入量增高可增强PPF骨水泥力学性能,扫描电镜下可观察到MC3T3-E1在材料在骨水泥表面粘附生长良好,随着HA投入量增加,其细胞数目也增加,通过检测成骨分化及矿化结果显示,空白组、PPF、PPF/10%HA、PPF/20%HA、PPF/30%HA钙结节数目计数分别为101.00±3.60、100.33±3.05、115.00±2.00、141.66±11.93、155.00±3.00。随着HA的加入,骨水泥材料的降解速率逐渐减缓。结论 随着PPF分子量、HA含量和粒径的增加,骨水泥的抗压强度和弹性模量逐渐增强。然而,当HA含量超过20%时,骨水泥的力学强度反而下降。PPF(8 h)与粒径200 nm 20% HA配方,在PPF与DMPT按1∶1条件下,其力学性能最佳,同时具备良好的生物相容性。
英文摘要:
      Objective To explore the formulation of a novel absorbable bone cement made from polypropylene fumarate (PPF) and hydroxyapatite (HA), and to evaluate its in vitro bioactivity.Methods PPF was synthesized using a two-step method. The number-average molecular weight, weight-average molecular weight, and polydispersity index (PDI) of PPF were determined by gel permeation chromatography (GPC). The structure of PPF was analyzed by proton nuclear magnetic resonance (1H NMR). Various formulations of PPF/HA bone cement were prepared, including PPF with different molecular weights (6 h, 8 h), PPF (8 h) with DMPT in 1∶1 and 1∶10 ratios, PPF with different particle sizes of hydroxyapatite, and PPF/HA formulations with varying ratios (100∶10, 100∶20, 100∶30). The mechanical properties and in vitro biocompatibility of the bone cements were further investigated.Results PPF was successfully synthesized via the two-step method. Nitrogen protection and oil pumps reduced the molecular weight distribution (polydispersity, PD) value and accelerated the reaction; however, when the reaction time exceeded 24 h, the molecular weight decreased. The addition of nano-hydroxyapatite enhanced the mechanical properties of the PPF bone cement. The compressive strengths for formulations 1-7 were (95.08±3.40), (119.80±9.57), (84.00±6.36), (116.80±6.94), (125.60±4.09), (147.00±4.30), and (130.40±2.88) MPa, respectively. The elastic moduli were (804.60±15.38), (855.00±16.94), (729.80±40.19), (883.20±6.22), (896.00±7.68), (976.80±18.36), and (920.00±8.83) MPa, respectively. Scanning electron microscopy (SEM) images showed good adhesion and growth of MC3T3-E1 cells on the surface of the bone cement. As the HA content increased, the number of cells also increased. Osteogenic differentiation and mineralization tests showed that the number of calcium nodules for the blank group, PPF, PPF/10%HA, PPF/20%HA, and PPF/30%HA were 101.00±3.60, 100.33±3.05, 115.00±2.00, 141.66±11.93, and 155.00±3.00, respectively. The degradation of PPF in PBS showed a weight loss of (1.41±0.01)% after the first week, and a total weight loss of (7.57±0.06)% over the first four weeks. With the addition of HA, the degradation rate of PPF decreased. The PPF/30%HA composite showed a weight loss of (1.20±0.036)% after the first week and a total weight loss of (5.36±0.08)% over the first four weeks.Conclusion As the molecular weight of PPF, the content and particle size of HA increase, the compressive strength and elastic modulus of the bone cement improve. However, when the HA content exceeds 20%, the mechanical strength of the bone cement decreases. The PPF (8 h) with 200 nm HA at a 100∶20 ratio and in a 1∶1 PPF/DMPT system exhibited the best mechanical properties and good biocompatibility.
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