Journal Home > Volume 1 , Issue 2–4

Nanocrystalline hydroxyapatite has been extensively used for biomedical field, such as drug carrier, antitumor agent, surface coating, and bone-regenerating material. The wet chemical method is one of the most commonly used methods in the synthesis of nanosized hydroxyapatite due to its relatively low costs and more customizable control of the final product. Herein, we updated the most recent advances in artificial nano-hydroxyapatite prepared from biomimetic precipitation throughout context. Furthermore, micron-sized particles and macro-sized scaffolds made of nano-hydroxyapatite deposition are introduced. Their outstanding physicochemical properties and potential clinical application are highlighted. This article reviews the latest progress on preparing biomimetic nano-hydroxyapatite and provides inspiration to promote new breakthrough in regenerative therapy and clinical translation.


menu
Abstract
Full text
Outline
About this article

Biomimetically precipitated nanocrystalline hydroxyapatite

Show Author's information Ben Wan1,2,§Yan Ruan1,§Chenxi Shen1Gaoli Xu1,3Tymour Forouzanfar1Haiyan Lin2,4( )Gang Wu1 ( )
Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam (VU), Amsterdam Movement Science (AMS), Amsterdam 1000, the Netherlands
Department of Stomatology, Hangzhou Medical College, Hangzhou 310000, China
Department of Stomatology, Zhejiang Hospital, Hangzhou 310000, China
Department of Stomatology, Hangzhou Stomatology Hospital, Hangzhou 310000, China

§ Ben Wan and Yan Ruan contributed equally to this work.

Abstract

Nanocrystalline hydroxyapatite has been extensively used for biomedical field, such as drug carrier, antitumor agent, surface coating, and bone-regenerating material. The wet chemical method is one of the most commonly used methods in the synthesis of nanosized hydroxyapatite due to its relatively low costs and more customizable control of the final product. Herein, we updated the most recent advances in artificial nano-hydroxyapatite prepared from biomimetic precipitation throughout context. Furthermore, micron-sized particles and macro-sized scaffolds made of nano-hydroxyapatite deposition are introduced. Their outstanding physicochemical properties and potential clinical application are highlighted. This article reviews the latest progress on preparing biomimetic nano-hydroxyapatite and provides inspiration to promote new breakthrough in regenerative therapy and clinical translation.

Keywords: biomedical application, biofabrication, biomimetic, nano-hydroxyapatite

References(67)

[1]

Baldwin, P.; Li, D. J.; Auston, D. A.; Mir, H. S.; Yoon, R. S.; Koval, K. J. Autograft, allograft, and bone graft substitutes: Clinical evidence and indications for use in the setting of orthopaedic trauma surgery. J. Orthop. Trauma 2019, 33, 203–213.

[2]

Singh, G.; Singh, R. P.; Jolly, S. S. Customized hydroxyapatites for bone-tissue engineering and drug delivery applications: A review. J. Sol-Gel Sci. Technol. 2020, 94, 505–530.

[3]

Balu, S. K.; Andra, S.; Jeevanandam, J.; Vidyavathy, S. M.; Sampath, V. Emerging marine derived nanohydroxyapatite and their composites for implant and biomedical applications. J. Mech. Behav. Biomed. Mater. 2021, 119, 104523.

[4]

Zhou, H. J.; Lee, J. Nanoscale hydroxyapatite particles for bone tissue engineering. Acta Biomater. 2011, 7, 2769–2781.

[5]

He, J. Y.; Shen, M. J.; Wan, Q. Q.; Zhang, Y. S.; Xiao, Y. H.; Wei, J. H.; Liu, Y.; Yan, J. F.; Wan, M. C.; Xu, K. H. et al. The janus nature of nanohydroxyapatite in tumor progression. Adv. Funct. Mater. 2022, 32, 2107599.

[6]

Nayak, B.; Samant, A.; Misra, P. K.; Saxena, M. Nanocrystalline hydroxyapatite: A potent material for adsorption, biological and catalytic studies. Mater. Today: Proc. 2019, 9, 689–698.

[7]

Pan, Y. S.; Xiong, D. S.; Chen, X. L. Mechanical properties of nanohydroxyapatite reinforced poly(vinyl alcohol) gel composites as biomaterial. J. Mater. Sci. 2007, 42, 5129–5134.

[8]

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. et al. Application of hydroxyapatite nanoparticles in tumor-associated bone segmental defect. Sci. Adv. 2019, 5, eaax6946.

[9]

Javadinejad, H. R.; Rizi, M. S.; Mobarakeh, E. A.; Ebrahimian, M. Thermal stability of nano-hydroxyapatite synthesized via mechanochemical treatment. Arab. J. Sci. Eng. 2017, 42, 4401–4408.

[10]

Balázsi, C.; Gergely, G.; Balázsi, K.; Chae, C. H.; Sim, H. Y.; Choi, J. Y.; Kim, S. G. Bone formation with nano-hydroxyapatite from eggshell. Mater. Sci. Forum 2012, 729, 25–30.

[11]

Sharifianjazi, F.; Esmaeilkhanian, A.; Moradi, M.; Pakseresht, A.; Asl, M. S.; Karimi-Maleh, H.; Jang, H. W.; Shokouhimehr, M.; Varma, R. S. Biocompatibility and mechanical properties of pigeon bone waste extracted natural nano-hydroxyapatite for bone tissue engineering. Mater. Sci. Eng. : B 2021, 264, 114950.

[12]

Yeong, K. C. B.; Wang, J.; Ng, S. C. Mechanochemical synthesis of nanocrystalline hydroxyapatite from CaO and CaHPO4. Biomaterials 2001, 22, 2705–2712.

[13]

Zakaria, S. M.; Zein, S. H. S.; Othman, M. R.; Yang, F.; Jansen, J. A. Nanophase hydroxyapatite as a biomaterial in advanced hard tissue engineering: A review. Tissue Eng. Part B: Rev. 2013, 19, 431–441.

[14]

Bala, Y.; Farlay, D.; Boivin, G. Bone mineralization: From tissue to crystal in normal and pathological contexts. Osteoporos. Int. 2013, 24, 2153–2166.

[15]

Kokubo, T.; Kushitani, H.; Sakka, S.; Kitsugi, T.; Yamamuro, T. Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W3. J. Biomed. Mater. Res. 1990, 24, 721–734.

[16]

Kokubo, T.; Takadama, H. How useful is SBF in predicting in vivo bone bioactivity?. Biomaterials 2006, 27, 2907–2915.

[17]

Lin, X. N.; Chen, J. P.; Liao, Y.; Pathak, J. L.; Li, H.; Liu, Y. L. Biomimetic calcium phosphate coating as a drug delivery vehicle for bone tissue engineering: A mini-review. Coatings 2020, 10, 1118.

[18]

Leena, M.; Rana, D.; Webster, T. J.; Ramalingam, M. Accelerated synthesis of biomimetic nano hydroxyapatite using simulated body fluid. Mater. Chem. Phys. 2016, 180, 166–172.

[19]

Cengiz, B.; Gokce, Y.; Yildiz, N.; Aktas, Z.; Calimli, A. Synthesis and characterization of hydroxyapatite nanoparticles. Colloids Surf. A: Physicochem. Eng. Aspects 2008, 322, 29–33.

[20]

Nayar, S.; Sinha, M. K.; Basu, D.; Sinha, A. Synthesis and sintering of biomimetic hydroxyapatite nanoparticles for biomedical applications. J. Mater. Sci. : Mater. Med. 2006, 17, 1063–1068.

[21]

Sinha, A.; Nayar, S.; Agrawal, A.; Bhattacharyya, D.; Ramachandrarao, P. Synthesis of nanosized and microporous precipitated hydroxyapatite in synthetic polymers and biopolymers. J. Am. Ceram. Soc. 2003, 86, 357–359.

[22]

Cui, F. Z.; Li, Y.; Ge, J. Self-assembly of mineralized collagen composites. Mater. Sci. Eng. : R: Rep. 2007, 57, 1–27.

[23]

Zhai, Y.; Cui, F. Z.; Wang, Y. Formation of nano-hydroxyapatite on recombinant human-like collagen fibrils. Curr. Appl. Phys. 2005, 5, 429–432.

[24]

Wang, S.; Yang, Y. D.; Koons, G. L.; Mikos, A. G.; Qiu, Z. Y.; Song, T. X.; Cui, F. Z.; Wang, X. M. Tuning pore features of mineralized collagen/PCL scaffolds for cranial bone regeneration in a rat model. Mater. Sci. Eng. : C 2020, 106, 110186.

[25]

Chaudhuri, B.; Mondal, B.; Modak, D. K.; Pramanik, K.; Chaudhuri, B. K. Preparation and characterization of nanocrystalline hydroxyapatite from egg shell and K2HPO4 solution. Mater. Lett. 2013, 97, 148–150.

[26]

Venkatesan, J.; Lowe, B.; Manivasagan, P.; Kang, K. H.; Chalisserry, E. P.; Anil, S.; Kim, D. G.; Kim, S. K. Isolation and characterization of nano-hydroxyapatite from salmon fish bone. Materials 2015, 8, 5426–5439.

[27]

Arokiasamy, P.; Al Bakri Abdullah, M. M.; Abd Rahim, S. Z.; Luhar, S.; Sandu, A. V.; Jamil, N. H.; Nabiałek, M. Synthesis methods of hydroxyapatite from natural sources: A review. Ceram. Int. 2022, 48, 14959–14979.

[28]

Boonyang, U.; Chaopanich, P.; Wongchaisuwat, A.; Senthongkaew, P.; Siripaisarnpipat, S. Effect of phosphate precursor on the production of hydroxyapatite from crocodile eggshells. J. Biomim. Biomater. Tissue Eng. 2010, 5, 31–37.

[29]

Ishtiaque, M. S.; Das, H.; Hoque, S. M.; Choudhury, S. Synthesis of n-HAP using different precursors and dependence of Vickers hardness on the structure by tuning sintering temperature. Int. J. Appl. Ceram. Technol. 2022, 19, 1281–1292.

[30]

Wang, P. P.; Li, C. H.; Gong, H. Y.; Jiang, X. R.; Wang, H. Q.; Li, K. X. Effects of synthesis conditions on the morphology of hydroxyapatite nanoparticles produced by wet chemical process. Powder Technol. 2010, 203, 315–321.

[31]

Vilela, H. S.; Rodrigues, M. C.; Fronza, B. M.; Trinca, R. B.; Vichi, F. M.; Braga, R. R. Effect of temperature and pH on calcium phosphate precipitation. Cryst. Res. Technol. 2021, 56, 2100094.

[32]

Ressler, A.; Žužić, A.; Ivanišević, I.; Kamboj, N.; Ivanković, H. Ionic substituted hydroxyapatite for bone regeneration applications: A review. Open Ceram. 2021, 6, 100122.

[33]

Paz, A.; Guadarrama, D.; López, M.; González, J. E.; Brizuela, N.; Aragón, J. A comparative study of hydroxyapatite nanoparticles synthesized by different routes. Quím. Nova 2012, 35, 1724–1727.

[34]

Li, H.; Guo, Z. Z.; Xue, B.; Zhang, Y. M.; Huang, W. Y. Collagen modulating crystallization of apatite in a biomimetic gel system. Ceram. Int. 2011, 37, 2305–2310.

[35]

Wang, F.; Li, M. S.; Lu, Y. P.; Qi, Y. X. A simple sol-gel technique for preparing hydroxyapatite nanopowders. Mater. Lett. 2005, 59, 916–919.

[36]

Liu, T. Y.; Chen, S. Y.; Liu, D. M.; Liou, S. C. On the study of BSA-loaded calcium-deficient hydroxyapatite nano-carriers for controlled drug delivery. J. Control. Release 2005, 107, 112–121.

[37]

Garnett, J.; Dieppe, P. The effects of serum and human albumin on calcium hydroxyapatite crystal growth. Biochem. J. 1990, 266, 863–868.

[38]

Wang, R. X.; Hu, H.; Guo, J. X.; Wang, Q.; Cao, J. J.; Wang, H. G.; Li, G. P.; Mao, J. P.; Zou, X. N.; Chen, D. F. et al. Nano-hydroxyapatite modulates osteoblast differentiation through autophagy induction via mTOR signaling pathway. J. Biomed. Nanotechnol. 2019, 15, 405–415.

[39]

Mocanu, A.; Balint, R.; Garbo, C.; Timis, L.; Petean, I.; Horovitz, O.; Tomoaia-Cotisel, M. Low crystallinity nanohydroxyapatite prepared at room temperature. Stud. Univ. Babes-Bolyai Chem. 2017, 62, 95–103.

[40]

Zhang, H. Q.; Zhang, M. Characterization and thermal behavior of calcium deficient hydroxyapatite whiskers with various Ca/P ratios. Mater. Chem. Phys. 2011, 126, 642–648.

[41]

Zhang, L. H.; Lu, T. L.; He, F. P.; Zhang, W. M.; Yuan, X. Y.; Wang, X. L.; Ye, J. D. Physicochemical and cytological properties of poorly crystalline calcium-deficient hydroxyapatite with different Ca/P ratios. Ceram. Int. 2022, 48, 24765–24776.

[42]

Zhao, X. X.; Ng, S.; Heng, B. C.; Guo, J.; Ma, L.; Tan, T. T. Y.; Ng, K. W.; Loo, S. C. J. Cytotoxicity of hydroxyapatite nanoparticles is shape and cell dependent. Arch. Toxicol. 2013, 87, 1037–1052.

[43]

Cai, Y. R.; Liu, Y. K.; Yan, W. Q.; Hu, Q. H.; Tao, J. H.; Zhang, M.; Shi, Z. L.; Tang, R. K. Role of hydroxyapatite nanoparticle size in bone cell proliferation. J. Mater. Chem. 2007, 17, 3780–3787.

[44]

Li, Y. L.; Wang, Y. Q.; Li, Y. M.; Luo, W.; Jiang, J.; Zhao, J. Z.; Liu, C. S. Controllable synthesis of biomimetic hydroxyapatite nanorods with high osteogenic bioactivity. ACS Biomater. Sci. Eng. 2020, 6, 320–328.

[45]

Xu, G. L.; Shen, C. X.; Lin, H. Y.; Zhou, J.; Wang, T.; Wan, B.; Binshabaib, M.; Forouzanfar, T.; Xu, G. C.; Alharbi, N. et al. Development, in-vitro characterization and in-vivo osteoinductive efficacy of a novel biomimetically-precipitated nanocrystalline calcium phosphate with internally-incorporated bone morphogenetic protein-2. Front. Bioeng. Biotechnol. 2022, 10, 920696.

[46]

Wu, G.; Liu, Y. L.; Iizuka, T.; Hunziker, E. B. Biomimetic coating of organic polymers with a protein-functionalized layer of calcium phosphate: The surface properties of the carrier influence neither the coating characteristics nor the incorporation mechanism or release kinetics of the protein. Tissue Eng. Part C: Methods 2010, 16, 1255–1265.

[47]

Zheng, Y. N.; Wu, G.; Liu, T.; Liu, Y.; Wismeijer, D.; Liu, Y. L. A novel BMP2-coprecipitated, layer-by-layer assembled biomimetic calcium phosphate particle: A biodegradable and highly efficient osteoinducer. Clin. Implant Dent. Relat. Res. 2014, 16, 643–654.

[48]

Liu, T.; Wu, G.; Zheng, Y. N.; Wismeijer, D.; Everts, V.; Liu, Y. L. Cell-mediated BMP-2 release from a novel dual-drug delivery system promotes bone formation. Clin. Oral Implants Res. 2014, 25, 1412–1421.

[49]

Wang, D.; Tabassum, A.; Wu, G.; Deng, L.; Wismeijer, D.; Liu, Y. Bone regeneration in critical-sized bone defect enhanced by introducing osteoinductivity to biphasic calcium phosphate granules. Clin. Oral Implants Res. 2017, 28, 251–260.

[50]

Liu, T.; Zheng, Y. N.; Wu, G.; Wismeijer, D.; Pathak, J. L.; Liu, Y. L. BMP2-coprecipitated calcium phosphate granules enhance osteoinductivity of deproteinized bovine bone, and bone formation during critical-sized bone defect healing. Sci. Rep. 2017, 7, 41800.

[51]

Zhu, W. M.; Xiao, J. D.; Wang, D. P.; Liu, J. Q.; Xiong, J. Y.; Liu, L. J.; Zhang, X. J.; Zeng, Y. J. Experimental study of nano-HA artificial bone with different pore sizes for repairing the radial defect. Int. Orthop. 2009, 33, 567–571.

[52]

Zhu, W. M.; Wang, D. P.; Zhang, X. J.; Lu, W.; Han, Y.; Ou, Y. K.; Zhou, K.; Fen, W.; Liu, J. Q.; Peng, L. Q. et al. Experimental study of nano-hydroxyapatite/recombinant human bone morphogenetic protein-2 composite artificial bone. Artif. Cells Blood Substit. Biotechnol. 2010, 38, 150–156.

[53]

Zhu, W. M.; Wang, D. P.; Xiong, J. Y.; Liu, J. Q.; You, W.; Huang, J. H.; Duan, L.; Chen, J. L.; Zeng, Y. J. Study on clinical application of nano-hydroxyapatite bone in bone defect repair. Artif. Cells Nanomed. Biotechnol. 2015, 43, 361–365.

[54]

Smith, I. O.; McCabe, L. R.; Baumann, M. J. MC3T3-E1 osteoblast attachment and proliferation on porous hydroxyapatite scaffolds fabricated with nanophase powder. Int. J. Nanomedicine 2006, 1, 189–194.

[55]

Kim, C.; Lee, J. W.; Heo, J. H.; Park, C.; Kim, D. H.; Yi, G. S.; Kang, H. C.; Jung, H. S.; Shin, H.; Lee, J. H. Natural bone-mimicking nanopore-incorporated hydroxyapatite scaffolds for enhanced bone tissue regeneration. Biomater. Res. 2022, 26, 7.

[56]

Lian, M. F.; Sun, B. B.; Han, Y.; Yu, B.; Xin, W. W.; Xu, R. D.; Ni, B.; Jiang, W. B.; Hao, Y. Q.; Zhang, X. Y. et al. A low-temperature-printed hierarchical porous sponge-like scaffold that promotes cell-material interaction and modulates paracrine activity of MSCs for vascularized bone regeneration. Biomaterials 2021, 274, 120841.

[57]

Liu, X.; Miao, Y. L.; Liang, H. F.; Diao, J. J.; Hao, L. J.; Shi, Z. F.; Zhao, N. R.; Wang, Y. J. 3D-printed bioactive ceramic scaffolds with biomimetic micro/nano-HAp surfaces mediated cell fate and promoted bone augmentation of the bone–implant interface in vivo. Bioact. Mater. 2022, 12, 120–132.

[58]

Mahanty, A.; Shikha, D. Changes in the morphology, mechanical strength and biocompatibility of polymer and metal/polymer fabricated hydroxyapatite for orthopaedic implants: A review. J. Polym. Eng. 2022, 42, 298–322.

[59]

Che, Y. L.; Min, S.; Wang, M. H.; Rao, M. Y.; Quan, C. Y. Biological activity of hydroxyapatite/poly(methylmethacrylate) bone cement with different surface morphologies and modifications for induced osteogenesis. J. Appl. Polym. Sci. 2019, 136, 48188.

[60]

Tank, K. P.; Chudasama, K. S.; Thaker, V. S.; Joshi, M. J. Pure and zinc doped nano-hydroxyapatite: Synthesis, characterization, antimicrobial and hemolytic studies. J. Cryst. Growth 2014, 401, 474–479.

[61]

de Carvalho, F. G.; Vieira, B. R.; dos Santos, R. L.; Carlo, H. L.; Lopes, P. Q.; de Lima, B. A. S. G. In vitro effects of nano-hydroxyapatite paste on initial enamel carious lesions. Pediatr. Dent. 2014, 36, 85–89.

[62]

Vano, M.; Derchi, G.; Barone, A.; Genovesi, A.; Covani, U. Tooth bleaching with hydrogen peroxide and nano-hydroxyapatite: A 9-month follow-up randomized clinical trial. Int. J. Dent. Hyg. 2015, 13, 301–307.

[63]

Shaikh, M. S.; Zafar, M. S.; Alnazzawi, A. Comparing nanohydroxyapatite graft and other bone grafts in the repair of periodontal infrabony lesions: A systematic review and meta-analysis. Int. J. Mol. Sci. 2021, 22, 12021.

[64]

Cheng, Z. P.; Guo, C. H.; Dong, W. J.; He, F. M.; Zhao, S. F.; Yang, G. L. Effect of thin nano-hydroxyapatite coating on implant osseointegration in ovariectomized rats. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2012, 113, e48–e53.

[65]

Pang, K. M.; Seo, Y. K.; Lee, J. H. Effects of the combination of bone morphogenetic protein-2 and nano-hydroxyapatite on the osseointegration of dental implants. J. Korean Assoc. Oral Maxillofac. Surg. 2021, 47, 454–464.

[66]

Jimbo, R.; Coelho, P. G.; Bryington, M.; Baldassarri, M.; Tovar, N.; Currie, F.; Hayashi, M.; Janal, M. N.; Andersson, M.; Ono, D. et al. Nano hydroxyapatite-coated implants improve bone nanomechanical properties. J. Dent. Res. 2012, 91, 1172–1177.

[67]

Sadjadi, M. A. S.; Meskinfam, M.; Sadeghi, B.; Jazdarreh, H.; Zare, K. In situ biomimetic synthesis and characterization of nano hydroxyapatite in gelatin matrix. J. Biomed. Nanotechnol. 2011, 7, 450–454.

Publication history
Copyright
Rights and permissions

Publication history

Received: 13 July 2022
Revised: 08 August 2022
Accepted: 12 August 2022
Published: 07 November 2022
Issue date: December 2022

Copyright

© The Author(s) 2022. Nano TransMed published by Tsinghua University Press.

Rights and permissions

The articles published in this open access journal are distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Return