羟基磷灰石基复合骨修复材料的仿生设计策略及研究进展

doi:10.13701/j.cnki.kqyxyj.2026.10.001

摘要/Abstract

摘要： 羟基磷灰石(hydroxyapatite, HA)作为骨组织的主要无机成分,具有优异的生物相容性和骨传导性,因此在骨修复领域中得到广泛应用。然而,传统人工合成的HA基复合骨修复材料在微观结构、结晶度及晶粒排列等方面与天然骨存在显著差异,导致其力学性能不足、骨整合能力有限。近年来,仿生材料学的兴起为HA复合材料的优化设计提供了新的思路。通过模拟天然骨的化学组成与多层次结构,仿生HA基复合骨修复材料在力学性能、细胞行为调控及成骨诱导方面展现出明显优势。本文首先阐述了仿生HA复合材料在骨修复领域的重要作用,分类回顾了HA基复合骨修复材料的仿生设计理念,重点探讨了材料诱导HA仿生矿化及结构仿生设计的最新研究进展,并对其未来发展方向进行了展望。

关键词: 羟基磷灰石类, 仿生材料, 骨再生

Abstract: As the main inorganic component of bone tissue, hydroxyapatite (HA) exhibits excellent biocompatibility and osteoconductivity, thus being widely applied in bone tissue engineering. However, there are significant differences between traditionally synthetic HA-based composite bone repair materials and natural bone in terms of microstructure, crystallinity, and grain orientation. These differences result in insufficient mechanical properties and limited osseointegration ability of the synthetic materials. In recent years, the rise of biomimetic material science has provided new insights for the optimal design of HA composite materials. By simulating the chemical composition and multi-level structure of natural bone, biomimetic HA-based composite bone repair materials demonstrate distinct advantages in mechanical properties, cell behavior regulation, and osteogenic induction. This article first expounds the important role of biomimetic HA composite materials in the field of bone repair, then retrospectively categorizes the biomimetic design concepts of HA-based composite bone repair materials, focuses on the latest research progress in material-induced HA biomimetic mineralization and structural biomimetic design, and finally provides an outlook on their future development directions.

Key words: hydroxyapatites, biomimetic materials, bone regeneration

卜金, 包崇云. 羟基磷灰石基复合骨修复材料的仿生设计策略及研究进展[J]. 口腔医学研究, 2026, 42(10): 827-832.

BU Jin, BAO Chongyun. Biomimetic Design Strategies and Research Progress of Hydroxyapatite-based Composite Bone Repair Materials.[J]. Journal of Oral Science Research, 2026, 42(10): 827-832.

参考文献

[1] Danesi AL, Athanasiadou D, Mansouri A, et al. Uniaxial hydroxyapatite growth on a self-assembled protein scaffold[J]. Int J Mol Sci, 2021, 22(22): 12343.
[2] Verma R, Mishra SR, Gadore V, et al. Hydroxyapatite-based composites: Excellent materials for environmental remediation and biomedical applications[J]. Adv Colloid Interface Sci, 2023, 315: 102890.
[3] Mondal S, Park S, Choi J, et al. Hydroxyapatite: A journey from biomaterials to advanced functional materials[J]. Adv Colloid Interface Sci, 2023, 321: 103013.
[4] Wan F, Ping H, Wang W, et al. Hydroxyapatite-reinforced alginate fibers with bioinspired dually aligned architectures[J]. Carbohydr Polym, 2021, 267: 118167.
[5] Lama M, Merle M, Bessot E, et al. Hierarchical collagen/apatite co-assembly for injection of mineralized fibrillar tissue analogues[J]. ACS Biomater Sci Eng, 2025, 11(1): 564-576.
[6] Li M, Cheng G, Xiao S, et al. Biomimetic mineralized hydroxyapatite-fish-scale collagen/chitosan nanofibrous membranes promote osteogenesis for periodontal tissue regeneration[J]. ACS Biomater Sci Eng, 2024, 10(8): 5108-5121.
[7] Gong M, Liu C, Liu C, et al. Biomimetic hydroxyapate/polydopamine composites with good biocompatibility and efficiency for uncontrolled bleeding[J]. J Biomed Mater Res B Appl Biomater, 2021, 109(11): 1876-1892.
[8] Nudelman F, Pieterse K, George A, et al. The role of collagen in bone apatite formation in the presence of hydroxyapatite nucleation inhibitors[J]. Nat Mater, 2010, 9(12): 1004-1009.
[9] Kim D, Lee J, Kim G. Biomimetic gelatin/HA biocomposites with effective elastic properties and 3D-structural flexibility using a 3D-printing process[J]. Addit Manuf, 2020, 36: 101616.
[10] Han D, Wang W, Gong J, et al. Collagen-hydroxyapatite based scaffolds for bone trauma and regeneration: recent trends and future perspectives[J]. Nanomedicine (Lond), 2024, 19(18-20): 1689-1709.
[11] Wang L, Chen X, Wang X, et al. Bio-inspired mineralized collagen scaffolds with precisely controlled gradients for the treatment of severe osteoarthritis in a male rabbit model[J]. Int J Biol Macromol, 2025, 300: 139843.
[12] Ong R, Cornish J, Wen J. Nanoparticular and other carriers to deliver lactoferrin for antimicrobial, antibiofilm and bone-regenerating effects: a review[J]. BioMetals, 2023, 36(3): 709-727.
[13] 李蒙,戴梦男,俞杨销,等.丝素蛋白基骨修复材料的应用研究进展[J].纺织学报,2024,45(10): 224-231.
[14] Jin S, Fu X, Zeng W, et al. Chopped fibers and nano-hydroxyapatite enhanced silk fibroin porous hybrid scaffolds for bone augmentation[J]. J Mater Chem B, 2023, 11(7): 1557-1567.
[15] Manan S, Ullah MW, Ul-Islam M, et al. Bacterial cellulose: Molecular regulation of biosynthesis, supramolecular assembly, and tailored structural and functional properties[J]. Prog Mater Sci, 2022, 129: 100972.
[16] Zhang W, Wang XC, Li XY, et al. A 3D porous microsphere with multistage structure and component based on bacterial cellulose and collagen for bone tissue engineering[J]. Carbohydr Polym, 2020, 236: 116043.
[17] Buer Boyetey MJ, Torgbo S, Sukyai P. Bio-scaffold for bone tissue engineering with focus on bacterial cellulose, biological materials for hydroxyapatite synthesis and growth factors[J]. Eur Polym J, 2023, 194: 112168.
[18] Suneetha M, Kim H, Han SS. Bone-like apatite formation in biocompatible phosphate-crosslinked bacterial cellulose-based hydrogels for bone tissue engineering applications[J]. Int J Biol Macromol, 2024, 256(Pt 2): 128364.
[19] Wang X, Yang X, Xiao X, et al. Biomimetic design of platelet-rich plasma controlled release bacterial cellulose/hydroxyapatite composite hydrogel for bone tissue engineering[J]. Int J Biol Macromol, 2024, 269(Pt 2): 132124.
[20] Soriente A, Fasolino I, Gomez-Sánchez A, et al. Chitosan/hydroxyapatite nanocomposite scaffolds to modulate osteogenic and inflammatory response[J]. J Biomed Mater Res A, 2022, 110(2): 266-272.
[21] Ait Said H, Mabroum H, Lahcini M, et al. Manufacturing methods, properties, and potential applications in bone tissue regeneration of hydroxyapatite-chitosan biocomposites: a review[J]. Int J Biol Macromol, 2023, 243: 125150.
[22] El-Bahrawy NR, Elmekawy A, Salem ML, et al. Gelatin-hydroxyapatite-based hybrid composites: enhanced mechanical and biological characteristics through biomaterials integration for bone tissue engineering applications[J]. Int J Biol Macromol, 2025, 320: 145772.
[23] Huang J, Huang Z, Liang Y, et al. 3D printed gelatin/hydroxyapatite scaffolds for stem cell chondrogenic differentiation and articular cartilage repair[J]. Biomater Sci, 2021, 9(7): 2620-2630.
[24] Dasgupta S, Banerjee SS, Bandyopadhyay A, et al. Zn- and Mg-doped hydroxyapatite nanoparticles for controlled release of protein[J]. Langmuir, 2010, 26(7): 4958-4964.
[25] Chen S, Shi Y, Zhang X, et al. Biomimetic synthesis of Mg-substituted hydroxyapatite nanocomposites and three-dimensional printing of composite scaffolds for bone regeneration[J]. J Biomed Mater Res A, 2019, 107(11): 2512-2521.
[26] Zhang K, Liu Y, Zhao Z, et al. Magnesium-doped nano-hydroxyapatite/polyvinyl alcohol/chitosan composite hydrogel: preparation and characterization[J]. Int J Nanomedicine, 2024, 19: 651-671.
[27] Ma R, Fang L, Chen L, et al. Ferroptotic stress promotes macrophages against intracellular bacteria[J]. Theranostics, 2022, 12(5): 2266-2289.
[28] Yin M, Liu Z, Sun Z, et al. Biomimetic scaffolds regulating the iron homeostasis for remolding infected osteogenic microenvironment[J]. Adv Sci (Weinh), 2024, 11(44): e2407251.
[29] Stipniece L, Ramata-Stunda A, Vecstaudza J, et al. A comparative study on physicochemical properties and in vitro biocompatibility of sr-substituted and sr ranelate-loaded hydroxyapatite nanoparticles[J]. ACS Appl Bio Mater, 2023, 6(12): 5264-5281.
[30] Ge M, Ge K, Gao F, et al. Biomimetic mineralized strontium-doped hydroxyapatite on porous poly(L-lactic acid) scaffolds for bone defect repair[J]. Int J Nanomedicine, 2018, 13: 1707-1721.
[31] Liu S, Zheng Y, Liu R, et al. Preparation and characterization of a novel polylactic acid/hydroxyapatite composite scaffold with biomimetic micro-nanofibrous porous structure[J]. J Mater Sci Mater Med, 2020, 31(8): 74.
[32] 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.
[33] 苏绚丽,李震昊,王美艳,等.不同浓度纳米级羟基磷灰石对骨髓间充质干细胞的影响[J].石河子大学学报(自然科学版),2025,43(5): 596-603.
[34] Olza S, Hadj Bouzidi NM, Rubatat L, et al. Mineralized chitin nanocrystals enhance osteoinductive ability of chitosan 3D porous biohybrid scaffolds for bone tissue regeneration[J]. Carbohydr Polym, 2025, 366: 123911.
[35] Mo X, Zhang D, Liu K, et al. Nano-hydroxyapatite composite scaffolds loaded with bioactive factors and drugs for bone tissue engineering[J]. Int J Mol Sci, 2023, 24(2): 1291.
[36] Miao S, Guo J, Zhang Y, et al. Biomimetic intrafibrillar mineralization of hierarchically structured amyloid-like fibrils[J]. Adv Mater, 2025, 37(22): e2416824.
[37] Srivastav A, Chandanshive B, Dandekar P, et al. Biomimetic hydroxyapatite a potential universal nanocarrier for cellular internalization & drug delivery[J]. Pharm Res, 2019, 36(4): 60.
[38] Pitrolino KA, Felfel RM, Pellizzeri LM, et al. Development and in vitro assessment of a bi-layered chitosan-nano-hydroxyapatite osteochondral scaffold[J]. Carbohydr Polym, 2022, 282: 119126.
[39] Cui J, Yu X, Shen Y, et al. Electrospinning inorganic nanomaterials to fabricate bionanocomposites for soft and hard tissue repair[J]. Nanomaterials (Basel), 2023, 13(1): 204.
[40] Zeinali R, del Valle LJ, Torras J, et al. Recent progress on biodegradable tissue engineering scaffolds prepared by thermally-induced phase separation (TIPS)[J]. Int J Mol Sci, 2021, 22(7): 3504.
[41] Avanzi IR, Parisi JR, Souza A, et al. 3D-printed hydroxyapatite scaffolds for bone tissue engineering: a systematic review in experimental animal studies[J]. J Biomed Mater Res B Appl Biomater, 2023, 111(1): 203-219.
[42] Cámara-Torres M, Sinha R, Scopece P, et al. Tuning cell behavior on 3D scaffolds fabricated by atmospheric plasma-assisted additive manufacturing[J]. ACS Appl Mater Interfaces, 2021, 13(3): 3631-3644.
[43] Wojasiński M, Podgórski R, Kowalczyk P, et al. Mechanically suitable and osteoinductive 3D-printed composite scaffolds with hydroxyapatite nanoparticles having diverse morphologies for bone tissue engineering[J]. J Biomed Mater Res B Appl Biomater, 2024, 112(6): e35409.
[44] Singh I, Dixit K, Gupta P, et al. 3D-printed multifunctional Ag/CeO₂/ZnO reinforced hydroxyapatite-based scaffolds with effective antibacterial and mechanical properties[J]. ACS Appl Bio Mater, 2023, 6(12): 5210-5223.
[45] Zhang X, Wang Q, Zheng W, et al. Magnetic Fe₃O₄ nanoparticles modified hydroxyapatite whisker: a novel framework with superior osteogenic efficacy[J]. Adv Sci (Weinh), 2025, 12(39): e09715.