具有成骨和抗肿瘤功能的多孔聚醚醚酮复合支架的制备

Preparation of Porous Poly Ether Ether Ketone Composite Scaffolds with Osteogenic and Anti-tumor Functionalization

摘要

通过溶液沉淀法合成了羟基磷灰石纳米棒(nHAp)，模拟天然骨基质的无机成分，增强了材料的骨传导性；通过水热法合成了磷酸钼钴微米棒(CPMmr)，利用其介导的类芬顿反应催化过氧化氢生成羟基自由基，实现了对肿瘤细胞的有效杀伤；通过相转化法制备了具有连续贯通指状大孔和微米小孔的多孔聚醚醚酮(PEEK)支架，以促进细胞迁移、营养物质交换及组织长入.将CPMmr与nHAp均匀分散于甲基丙烯酯化的氧化透明质酸(AHAMA)与聚乙二醇甲醚甲基丙烯酸酯(PEGMA)复合水凝胶前驱液中，通过紫外光引发聚合将其接枝到多孔PEEK支架表面，合成了具有成骨活性及抗肿瘤功能的多孔PEEK复合支架.体外细胞实验结果表明，多孔PEEK复合支架对小鼠胚胎成骨细胞前体细胞(MC3T3-E1)具有良好的生物相容性，且能显著促进成骨相关基因的表达水平.此外，CPMmr可在肿瘤微环境中介导类芬顿反应，显著提升了人骨肉瘤细胞(MG-63)的氧化应激水平，导致活性氧积累并使肿瘤细胞凋亡，显示出良好的抗肿瘤效果.

Abstract

Hydroxyapatite nanorods（nHAp） were synthesized using a solution precipitation method to mimic the inorganic composition of natural bone matrix，enhancing the osteoconductivity of the material.Concurrently，cobalt molybdenum phosphate microrods（CPMmr） were synthesized through a hydrothermal method.Their mediated Fenton-like reaction can catalyze the conversion of hydrogen peroxide into hydroxyl radicals，achieving effective tumor cell killing.A porous polyether ether ketone（PEEK） scaffold with continuous interconnected finger-like macropores and micropores was prepared using phase inversion to promote cell migration，nutrient exchange，and tissue ingrowth.CPMmr and nHAp were uniformly dispersed in a composite hydrogel precursor solution of methylacrylated oxidized hyaluronic acid（AHAMA） and polyethylene glycol methacrylate（PEGMA），then they were grafted onto the porous PEEK scaffold surface through UV-initiated polymerization，synthesizing a porous PEEK composite scaffold with osteogenic activity and anti-tumor properties.In vitro cell experiments demonstrated that the porous PEEK composite scaffold exhibits excellent biocompatibility with mouse embryonic osteoblast precursor cells（MC3T3-E1） and significantly enhances the expression levels of osteogenesis-related genes.Furthermore，the presence of CPMmr mediates a Fenton-like reaction within the tumor microenvironment，significantly elevating oxidative stress levels in human osteosarcoma cells（MG-63）.This leads to reactive oxygen species accumulation and induces tumor cell apoptosis，demonstrating potent anti-tumor effect.

关键词

羟基磷灰石 / 磷酸钼钴微米棒 / 多孔聚醚醚酮 / 成骨活性 / 抗肿瘤效果

Key words

Hydroxyapatite / Cobalt molybdenum phosphate microrod / Porous poly ether ether ketone / Osteogenesis activity / Anti-tumor effect

参考文献

[1] Liang G.H., Wang W., Li C., Zhong B.L., Zhao L., Zhang Z.C., Liu J.X., Int. J. Nanomed., 2026, 21, 579152

[2] Gong H., Lu Z.F., Wei S.M., Rui Y.J., Colloid Surface B, 2026, 262, 115475

[3] Fan D.Y., Zhang C.Q., Wang H.F., Wei Q.G., Cai H., Wei F., Bian Z.L., Liu W.F., Wang X., Liu Z.J., Mater. Today Bio., 2023, 20, 100683

[4] He F.Z., Zhang W.B., Shen Y.H., Yu P., Bao Q.Y., Wen J.X., Hu C.Z., Qiu S.J., Int. J. Surg., 2016, 36, 283-292

[5] Liu J.Y., Tan R.H., Wang C.C., Li G.M., Zheng H., Wan Y., Int. J. Nanomed., 2026, 21, 1-19

[6] Zhang H., Tang W.S., Sui X., Li L.F., Zhang H.P., Li Y.R., Zhang X.Y., Liu Z.H., Wang B.W., Chem. Res. Chinese Universities, 2025, 41(1), 155-164

[7] Luo L., Gong Y.N., Yan L., Bu Y.Z., Chem. Res. Chinese Universities, 2024, 40(5), 786-797

[8] Ji Z.B., Wan Y., Wang H.W., Liang X.C., Appl. Mater. Today, 2026, 49, 103132

[9] Pant S., Loganathan S., Valapa R.B., Biomater. Adv., 2026, 182, 214705

[10] Deng B., Zhang D.C., Dai Y.L., Guo L., Lin S.H., Lin J.X., Tong X., Xiong W., Wright P., Li Y.C., Wen C.E., J. Mater. Sci. Technol., 2026, 265, 177-189

[11] Zeng S.X., Li H.Z., Hu P.P., Li Z.H., Wang Z.G., Wang J.D., Chen J.S., Wang S.Z., Wang G., Zhao W., Wei F., Biofabrication, 2025, 17, 035014

[12] Jeyachandran P., Lee L.Y.J., Hui S.J., Vellayappan B., Fuh J.Y.H., Hallinan J.T.P.D., Kumar A.S., Kumar N., ACS Appl. Mater. Interfaces, 2026, 18(6), 9411-9424

[13] Torstrick F.B., Lin A.S.P., Potter D., Safranski D.L., Sulchek T.A., Gall K., Guldberg R.E., Biomaterials, 2018, 185, 106-116

[14] Zheng Z., Liu P.J., Zhang X.M., Xin J.G., Wang Y.J., Zou X.S., Mei, X.H., Zhang S.L., Zhang S.K., Mater. Today Bio, 2022, 16, 100402

[15] An J.Y., Shi X.T., Zhang J., Qi L., Xue W., Nie X.Y., Yun Z.H., Zhang P.B., Liu Q.Y., Mater. Today Bio, 2024, 24, 100928

[16] Zheng J.B., Zhao H.Y., Ouyang Z.C., Zhou X.Y., Kang J.F., Yang C.C., Sun C.N., Xiong M.J., Fu M.Q., Jin D.D., Wang L., Li D.C., Li Q.C., Compos. Part. B: Eng., 2022, 232, 109508

[17] Hu L.Q., Ge Y.M., Cao Z., Tian Y., Sun Q.L., Li Z., Ma J., Wu Y.T., Wang N., Tang B., Biomater. Adv., 2022, 143, 213160

[18] Sikder P., Acta Biomater., 2025, 191, 29-52

[19] Lin H., Zhang L.Y., Ye X.T., Wang X., Han C.W., Yan Z.Q., Wang Q., Yan G.Q., Colloid. Surface B, 2025, 254, 114846

[20] Ma H.Y., Tong J., Su X.C., Liu L., Liang J.Q., Sun J.B., Lu J., Zhang Y.G., Lei B., Zhao H.M., Adv. Healthc. Mater., 2025, 14(9), 2404435

[21] Wei X.H., Zhou W.H., Tang Z., Wu H., Liu Y.C., Dong H., Wang N., Huang H., Bao S.S., Shi L., Li X.K., Zheng Y.F., Guo Z., Bioact. Mater., 2023, 20, 16-28

[22] Wang H.Z., Shu Z.X., Chen P., Su J., Zhu H., Jiang J.W., Yan C.Z., Xiao J., Shi Y.S., Acta Biomater., 2024, 189, 605-620

[23] Li X.J., Yuan Y., Liu L.Y., Leung Y.S., Chen Y.Y., Guo Y.X., Chai Y., Chen Y., Bio—des. Manuf., 2020, 3, 15-29

[24] Sabree I., Gough J.E., Derby B., Ceram. Int., 2015, 41(7), 8425-8432

[25] Yu H.Y., VandeVord P.J., Mao L., Matthew H.W., Wooley P.H., Yang S.Y., Biomaterials, 2009, 30(4), 508-517

[26] Zhao R., Chen J.Y., Li Y.J., Qian H., Zhu X.D., Maria G.R., Ambrosio L., Yang X., Zhang X.D., Bioact. Mater., 2026, 60, 640-660

[27] Lv S.Y., Yuan X., Xiao J., Jiang X.L., Carbohyd. Polym., 2023, 313, 120888

[28] Zhao D.W., Yu M.Z., Zhao Y.X., Hu R., Xu P.C., Sun Z.Y., Bian K., Liu C., Cheng L., J. Mater. Sci. Technol., 2023, 136, 109-120

[29] Li S., Yang R.N., Zhao Z.Y., Xie M.Z., Zhou Y., Zeng Q., Zhu X.D., Zhang X.D., Acta Biomater., 2025, 200, 87-114

[30] Zhang H.F., Qing F.Z., Zhao H., Fan H.S., Liu M., Zhang X.D., J. Mater. Chem. B, 2017, 5, 1205-1217

[31] Zhang K., Zhou Y., Xiao C., Zhao W.L., Wu H.F., Tang J.Q., Li Z.T., Yu S., Li X.F., Min L., Yu Z.T., Wang G., Wang L., Zhang K., Yang X., Zhu X.D., Tu C.Q., Zhang X.D., Sci. Adv., 2019, 5(8), eaax6946

[32] Cheng X.Y., Du X.F., Long J., Nie Y.Y., Du Y.H., Cheng L.Y., Li C.R., Zhao M.X., Lai Y.X., Zhang W., Colloid. Surface B, 2026, 262, 115505

[33] Feng L., Xu C., Zhao S.B., Peng Z.L., Jia Y.X., Tan G.H., Ji L., Zhou J., Chem. Eng. J., 2026, 529, 171709

[34] Wu C.Y., Liu Z.L., Chen Z.X., Xu D.L., Chen L.S., Lin H., Shi J.L., Sci. Adv., 2021, 7(39), eabj8833

[35] Sun Y.X., Zhou S.Y., Qin G.R., Guo J., Zhang Q.F., Li S.H., Zhang S.B., J. Membrane Sci., 2021, 620, 118899

[36] Chen J.Q., Yang J.B., Wang L., Guo J., Zhang X.W., He B.C., Wang D.A., Ge Z.G., Bioact. Mater., 2021, 6(6), 1689-1698

基金资助

国家自然科学基金(U23A20586)