磷酸钙陶瓷表面微结构对骨诱导的调控及机制研究进展

doi:10.19438/j.cjoms.2026.01.013

摘要/Abstract

摘要： 由创伤、肿瘤、先天畸形和感染等引起的临界骨缺损仍是临床治疗中的难题。磷酸钙陶瓷（calcium phosphate ceramics,CaPs）不仅促进骨缺损部位的骨形成,还能在异位（如肌肉和皮下组织）诱导新骨生成,有助于解决临界骨缺损修复问题。研究表明,表面微结构是影响CaPs骨诱导性的关键因素。本文综述了微结构特征对骨诱导能力的影响,分析了表面微结构在诱导异位骨形成中的作用机制,为未来CaPs材料的设计与临床应用提供理论指导。

关键词: 磷酸钙陶瓷, 表面微结构, 骨诱导, 机械转导, 免疫调控

Abstract: Critical bone defects caused by trauma, tumors, congenital malformations, infections, and other factors present significant challenges in clinical treatment. Calcium phosphate ceramics(CaPs) not only promote bone formation at the defect site but also induce ectopic bone formation in sites such as muscle and subcutaneous tissue, addressing challenges in repairing critical bone defects. The surface microstructure of CaPs is a key factor influencing their osteoinductive properties. This paper reviewed the impact of microstructural features on the osteoinductive potential of CaPs, explored the mechanisms by which surface microstructure induces ectopic bone formation, and provided theoretical insights for future design and clinical application of CaPs materials.

Key words: Calcium phosphate ceramics, Surface microstructure, Osteoinduction, Mechanical transduction, Immunomodulation

中图分类号:

R782.2
R318

王玥, 包崇云. 磷酸钙陶瓷表面微结构对骨诱导的调控及机制研究进展[J]. 中国口腔颌面外科杂志, 2026, 24(1): 83-88.

Wang Yue, Bao Chongyun. Progress in the regulation and mechanisms of osteoinduction by the surface microstructure of calcium phosphate ceramics[J]. China J Oral Maxillofac Surg, 2026, 24(1): 83-88.

参考文献

[1] Almulhim KS, Syed MR, Alqahtani N, et al.Bioactive inorganic materials for dental applications: a narrative review[J]. Materials (Basel), 2022, 15(19): 6864.
[2] Bohner M, Santoni BLG, Döbelin N.β-tricalcium phosphate for bone substitution: synthesis and properties[J]. Acta Biomater, 2020, 113: 23-41.
[3] Urist MR.Bone: formation by autoinduction[J]. Science, 1965, 150(3698): 893-899.
[4] Kokubo T, Yamaguchi S.Novel bioactive materials developed by simulated body fluid evaluation: surface-modified Ti metal and its alloys[J]. Acta Biomater, 2016, 44: 16-30.
[5] Guo X, Li M, Qi W, et al.Serial cellular events in bone formation initiated by calcium phosphate ceramics[J]. Acta Biomater, 2021, 134: 730-743.
[6] Galván-Chacón VP, de Melo Pereira D, Vermeulen S, et al. Decoupling the role of chemistry and microstructure in hMSCs response to an osteoinductive calcium phosphate ceramic[J]. Bioact Mater, 2023, 19: 127-138.
[7] Shen JZ, Kosmac T.Advanced ceramics for dentistry[M]. Oxford: Butterworth-Heinemann, 2014: 151-172.
[8] Xiao D, Zhang J, Zhang C, et al.The role of calcium phosphate surface structure in osteogenesis and the mechanisms involved[J]. Acta Biomater, 2020, 106: 22-33.
[9] Davison NL, Luo X, Schoenmaker T, et al.Submicron-scale surface architecture of tricalcium phosphate directs osteogenesis in vitro and in vivo[J]. Eur Cell Mater, 2014, 27: 281-297.
[10] Duan R, van Dijk LA, Barbieri D, et al. Accelerated bone formation by biphasic calcium phosphate with a novel sub-micron surface topography[J]. Eur Cell Mater, 2019, 37: 60-73.
[11] Zhang J, Dalbay MT, Luo X, et al.Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis[J]. Acta Biomater, 2017, 57: 487-497.
[12] Iaquinta MR, Torreggiani E, Mazziotta C, et al.In vitro osteoinductivity assay of hydroxylapatite scaffolds, obtained with biomorphic transformation processes, assessed using human adipose stem cell cultures[J]. Int J Mol Sci, 2021, 22(13): 7092.
[13] Li X, Liu M, Chen F, et al.Design of hydroxyapatite bioceramics with micro-/nano-topographies to regulate the osteogenic activities of bone morphogenetic protein-2 and bone marrow stromal cells[J]. Nanoscale, 2020, 12(13): 7284-7300.
[14] Xu D, Wan Y, Li Z, et al.Tailorable hierarchical structures of biomimetic hydroxyapatite micro/nano particles promoting endocytosis and osteogenic differentiation of stem cells[J]. Biomater Sci, 2020, 8(12): 3286-3300.
[15] Li M, Guo X, Qi W, et al.Macrophage polarization plays roles in bone formation instructed by calcium phosphate ceramics[J]. J Mater Chem B, 2020, 8(9): 1863-1877.
[16] Chen X, Wang M, Chen F, et al.Correlations between macrophage polarization and osteoinduction of porous calcium phosphate ceramics[J]. Acta Biomater, 2020, 103: 318-332.
[17] Zou M, Sun J, Xiang Z.Induction of M2-type macrophage differentiation for bone defect repair via an interpenetration network hydrogel with a GO-based controlled release system[J]. Adv Healthc Mater, 2021, 10(6): e2001502.
[18] Duan R, Zhang Y, van Dijk L, et al. Coupling between macrophage phenotype, angiogenesis and bone formation by calcium phosphates[J]. Mater Sci Eng C Mater Biol Appl, 2021, 122: 111948.
[19] Li M, Guo X, Qi W, et al.Macrophage polarization plays roles in bone formation instructed by calcium phosphate ceramics[J]. J Mater Chem B, 2020, 8(9): 1863-1877.
[20] Humbert P, Kampleitner C, De Lima J, et al.Phase composition of calcium phosphate materials affects bone formation by modulating osteoclastogenesis[J]. Acta Biomater, 2024, 176: 417-431.
[21] Davison NL, Gamblin AL, Layrolle P, et al.Liposomal clodronate inhibition of osteoclastogenesis and osteoinduction by submicrostructured beta-tricalcium phosphate[J]. Biomaterials, 2014, 35(19): 5088-5097.
[22] Jeong H, Kim D, Montagne K, et al.Differentiation-inducing effect of osteoclast microgrooves for the purpose of three-dimensional design of regenerated bone[J]. Acta Biomater, 2023, 168: 174-184.
[23] Akasaka T, Hayashi H, Tamai M, et al.Osteoclast formation from mouse bone marrow cells on micro/nano-scale patterned surfaces[J]. J Oral Biosci, 2022, 64(2): 237-244.
[24] Duan R, Barbieri D, Luo X, et al.Variation of the bone forming ability with the physicochemical properties of calcium phosphate bone substitutes[J]. Biomater Sci, 2017, 6(1): 136-145.
[25] Holland EN, Fernández-Yagüe MA, Zhou DW, et al.FAK, vinculin, and talin control mechanosensitive YAP nuclear localization[J]. Biomaterials, 2024, 308: 122542.
[26] Li N, Chen G, Liu J, et al.Effect of surface topography and bioactive properties on early adhesion and growth behavior of mouse preosteoblast MC3T3-E1 cells[J]. ACS Appl Mater Interfaces, 2014, 6(19): 17134-17143.
[27] Chen S, He T, Zhong Y, et al.Roles of focal adhesion proteins in skeleton and diseases[J]. Acta Pharm Sin B, 2023, 13(3): 998-1013.
[28] Chen Z, Zou Y, Lv Y.Dynamic-stiffening collagen-coated substrate enhances osteogenic differentiation of mesenchymal stem cells through integrin α2β1[J]. Biomater Sci, 2023, 11(13): 4700-4712.
[29] Guo Y, Ao Y, Ye C, et al.Nanotopographic micro-nano forces finely tune the conformation of macrophage mechanosensitive membrane protein integrin β2 to manipulate inflammatory responses[J]. Nano Res, 2023: 1-15.
[30] Yang Y, Lin Y, Xu R, et al.Micro/nanostructured topography on titanium orchestrates dendritic cell adhesion and activation via β2 Integrin-FAK signals[J]. Int J Nanomedicine, 2022, 17: 5117-5136.
[31] Hu D, Li T, Bian H, et al.Silk films with distinct surface topography modulate plasma membrane curvature to polarize macrophages[J]. Mater Today Bio, 2024, 28: 101193.
[32] Liu H, Wu Q, Liu S, et al.The role of integrin αvβ3 in biphasic calcium phosphate ceramics mediated M2 Macrophage polarization and the resultant osteoinduction[J]. Biomaterials, 2024, 304: 122406.
[33] Bouissou A, Proag A, Bourg N, et al.Podosome force generation machinery: a local balance between protrusion at the core and traction at the ring[J]. ACS Nano, 2017, 11(4): 4028-4040.
[34] Miron RJ, Bohner M, Zhang Y, et al.Osteoinduction and osteoimmunology: emerging concepts[J]. Periodontol 2000, 2024, 94(1): 9-26.
[35] Gou Y, Qi K, Wei Y, et al.Advances of calcium phosphate nanoceramics for the osteoinductive potential and mechanistic pathways in maxillofacial bone defect repair[J]. Nano TransMed, 2024, 3: 100033.
[36] Liu X, Hou W, He L, et al.AMOT130/YAP pathway in topography-induced BMSC osteoblastic differentiation[J]. Colloids Surf B Biointerfaces, 2019, 182: 110332.
[37] Tyrina E, Yakubets D, Markina E, et al.Hippo signaling pathway involvement in osteopotential regulation of murine bone marrow cells under simulated microgravity[J]. Cells, 2024, 13(22): 1921.
[38] Wei Q, Holle A, Li J, et al.BMP-2 signaling and mechanotransduction synergize to drive osteogenic differentiation via YAP/TAZ[J]. Adv Sci (Weinh), 2020, 7(15): 1902931.
[39] Pan JX, Xiong L, Zhao K, et al.YAP promotes osteogenesis and suppresses adipogenic differentiation by regulating β-catenin signaling[J]. Bone Res, 2018, 6: 18.
[40] Dupont S, Morsut L, Aragona M, et al.Role of YAP/TAZ in mechanotransduction[J]. Nature, 2011, 474(7350): 179-183.
[41] Mao Y, Wickström SA.Mechanical state transitions in the regulation of tissue form and function[J]. Nat Rev Mol Cell Biol, 2024, 25(8): 654-670.
[42] Wang H, Yu H, Huang T, et al.Hippo-YAP/TAZ signaling in osteogenesis and macrophage polarization: therapeutic implications in bone defect repair[J]. Genes Dis, 2023, 10(6): 2528-2539.
[43] Li L, Yang S, Xu L, et al.Nanotopography on titanium promotes osteogenesis via autophagy-mediated signaling between YAP and β-catenin[J]. Acta Biomater, 2019, 96: 674-685.
[44] Mei F, Guo Y, Wang Y, et al.Matrix stiffness regulates macrophage polarisation via the Piezo1-YAP signalling axis[J]. Cell Prolif, 2024, 57(8): e13640.
[45] Xiao B.Mechanisms of mechanotransduction and physiological roles of PIEZO channels[J]. Nat Rev Mol Cell Biol, 2024, 25(11): 886-903.
[46] Coste B, Mathur J, Schmidt M, et al.Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels[J]. Science, 2010, 330(6000): 55-60.
[47] Wang HJ, Wang Y, Mirjavadi SS, et al.Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution[J]. Nat Commun, 2024, 15(1): 5521.
[48] Yang X, Lin C, Chen X, et al.Structure deformation and curvature sensing of PIEZO1 in lipid membranes[J]. Nature, 2022, 604(7905): 377-383.
[49] Atcha H, Jairaman A, Holt JR, et al.Mechanically activated ion channel Piezo1 modulates macrophage polarization and stiffness sensing[J]. Nat Commun, 2021, 12(1): 3256.
[50] Yao H, Tang L, Wang D, et al.F-actin microfilaments affect the LIPUS-promoted osteogenic differentiation of BMSCs through TRPM7[J]. Biotechnol J, 2024, 19(8): e2400310.