Biomimetic hydroxyapatite coating on the 3D-printed bioactive porous composite ceramic scaffolds promoted osteogenic differentiation via PI3K/AKT/mTOR signaling pathways and facilitated bone regeneration in vivo

doi:10.1016/j.jmst.2022.07.016

J. Mater. Sci. Technol. ›› 2023, Vol. 136: 54-64.DOI: 10.1016/j.jmst.2022.07.016

• Research Article • Previous Articles Next Articles

Biomimetic hydroxyapatite coating on the 3D-printed bioactive porous composite ceramic scaffolds promoted osteogenic differentiation via PI3K/AKT/mTOR signaling pathways and facilitated bone regeneration in vivo

Bizhi Tan^a,1, Naru Zhao^b,c,1, Wei Guo^a, Fangli Huang^a, Hao Hu^a, Yan Chen^a, Jungang Li^a, Zemin Ling^a, Zhiyuan Zou^a, Rongcheng Hu^a, Chun Liu^a, Tiansheng Zheng^d, Gang Wang^a, Xiao Liu^a,*, Yingjun Wang^b,c,*, Xuenong Zou^a,*

^aGuangdong Provincial Key Laboratory of Orthopaedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China;
^bSchool of Materials Science and Engineering, South China University of Technology, Guangzhou 510641, China;
^cNational Engineering Research Center for Tissue Restoration and Reconstruction, Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, China;
^dDepartment of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China

Received:2022-04-12 Revised:2022-06-21 Accepted:2022-07-18 Published:2023-02-10 Online:2022-08-13
Contact: * E-mail addresses: liux539@mail.sysu.edu.cn (X. Liu), imwangyj@163.com (Y. Wang), zxnong@hotmail.com, zouxuen@mail.sysy.edu.cn (X. Zou).
About author:¹ These authors contributed equally to this work.

Abstract

Abstract: The architecture and surface modifications have been regarded as effective methods to enhance the biological response of biomaterials in bone tissue engineering. The porous architecture of the implantation was essential conditions for bone regeneration. Meanwhile, the design of biomimetic hydroxyapatite (HAp) coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate osteogenesis. However, bioactive bio-ceramics such as β-tricalcium phosphate (β-TCP) and calcium silicate (CS) with superior apatite-forming ability were reported to present better osteogenic activity than that of HAp. Hence in this study, 3D-printed interconnected porous bioactive ceramics β-TCP/CS scaffold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction, and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells (mBMSCs) and the potential mechanisms were explored. The results indicated that HAp apatite coating enhanced cell proliferation, alkaline phosphatase (ALP) activity, and osteogenic gene expression. Furthermore, PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular functions. The present results demonstrated that the key molecules of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) were activated after the biomimetic hydroxyapatite coating were constructed on the 3D-printed ceramic scaffolds. Besides, the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor HY-10358. In vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone quality. These results suggest that biomimetic HAp coating constructed on the 3D-printed bioactive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration.

Key words: Bioactive ceramics, Hydroxyapatite coating, 3D-printed porous ceramic scaffold, PI3K/AKT/mTOR signaling pathway, Bone regeneration

Bizhi Tan, Naru Zhao, Wei Guo, Fangli Huang, Hao Hu, Yan Chen, Jungang Li, Zemin Ling, Zhiyuan Zou, Rongcheng Hu, Chun Liu, Tiansheng Zheng, Gang Wang, Xiao Liu, Yingjun Wang, Xuenong Zou. Biomimetic hydroxyapatite coating on the 3D-printed bioactive porous composite ceramic scaffolds promoted osteogenic differentiation via PI3K/AKT/mTOR signaling pathways and facilitated bone regeneration in vivo[J]. J. Mater. Sci. Technol., 2023, 136: 54-64.

References

[1] P.P. Spicer, J.D. Kretlow, S. Young, J.A. Jansen, F.K. Kasper, A.G. Mikos, Nat. Pro- toc. 7(2012) 1918-1929.
[2] E. García-Gareta, M.J. Coathup, G.W. Blunn, Bone 81 (2015) 112-121.
[3] L.L. Hench, J.M. Polak, Science 295 (2002) 1014-1017.
[4] Z. Tang, X. Li, Y. Tan, H. Fan, X. Zhang, Regen. Biomater. 5(2018) 43-59.
[5] L.L Hench, R.J. Splinter, W.C. Allen, T.K Greenlee, J. Biomed. Mater. Res. Symp.(1971) 117-141.
[6] B. Wopenka, J.D. Pasteris, Mater. Sci. Eng. C Biomim.Supramol. Syst. 25(2005) 131-143.
[7] Y. Wu, Q. Li, B. Xu, H. Fu, Y. Li, Colloid Surf. B-Biointerfaces 207 (2021) 112019.
[8] J. Wang, M. Wang, F. Chen, Y. Wei, X. Chen, Y. Zhou, X. Yang, X. Zhu, C. Tu, X. Zhang, Int. J. Nanomed. 14 (2019) 7987-80 0 0.
[9] W. Chen, L. Nichols, F. Brinkley, K. Bohna, W. Tian, M.W. Priddy, L.B. Priddy, Mater. Sci. Eng. C 120 (2021) 111686.
[10] M. Bohner, J. Lemaitre, Biomaterials 30 (2009) 2175-2179.
[11] M. Alksne, M. Kalvaityte, E. Simoliunas, I. Rinkunaite, I. Gendviliene, J. Locs, V. Rutkunas, V. Bukelskiene, J. Mech. Behav.Biomed. Mater. 104(2020) 103641.
[12] R. Ge, C. Xun, J. Yang, W. Jia, Y. Li, Biomed. Mater. 14(2019) 065013.
[13] X. Li, M. Liu, F. Chen, Y. Wang, M. Wang, X. Chen, Y. Xiao, X. Zhang, Nanoscale 12 (2020) 7284-7300.
[14] V. Fitzpatrick, Z. Martín-Moldes, A. Deck, R. Torres-Sanchez, A. Valat, D. Cairns, C. Li, D.L. Kaplan, Biomaterials 276 (2021) 120995.
[15] A.R. Guntur, C.J. Rosen, J. Endocrinol. 211(2011) 123-130.
[16] Y. Tanaka, S. Sonoda, H. Yamaza, S. Murata, K. Nishida, S. Hama, Y. Kyumoto-Nakamura, N. Uehara, K. Nonaka, T. Kukita, T. Yamaza, Stem Cell Res. Ther. 9(2018) 334.
[17] Y. Sun, Y. Li, Y. Zhang, T. Wang, K. Lin, J. Liu, Mater. Sci. Eng. C 131 (2021) 112482.
[18] Y. Shi, R. He, X. Deng, Z. Shao, D. Deganello, C. Yan, Z. Xia, Biomater. Trans. 1(2020) 69-81.
[19] Y. Dong, H. Duan, N. Zhao, X. Liu, Y. Ma, X. Shi, Bio. Des. Manuf. 1(2018) 146-156.
[20] J. Diao, J. OuYang, T. Deng, X. Liu, Y. Feng, N. Zhao, C. Mao, Y. Wang, Adv. Healthc. Mater. 7(2018) e1800441.
[21] L. Xiao, N. Zhao, X. Guo, H. Duan, Y. Wang, CrystEngComm 21 (2019) 513-523.
[22] C.N. Kelly, T. Wang, J. Crowley, D. Wills, M.H. Pelletier, E.R. Westrick, S.B. Adams, K. Gall, W.R. Walsh, Biomaterials 279 (2021) 121206.
[23] H. Wang, J. Liu, C. Wang, S.G. Shen, X. Wang, K. Lin, J. Mater. Sci.Technol. 63(2021) 18-26.
[24] S.H. Um, J. Lee, I.S. Song, M.R. Ok, Y.C. Kim, H.S. Han, S.H. Rhee, H. Jeon, Bioact. Mater. 6(2021) 3608-3619.
[25] D. Ke, A .A. Vu, A.Bandyopadhyay, S. Bose, Acta Biomater. 84(2019) 414-423.
[26] X. Zhou, N. Zhang, S. Mankoci, N. Sahai, J. Biomed. Mater. Res. Part A 105 (2017) 2090-2102.
[27] X. Liu, Y. Miao, H. Liang, J. Diao, L. Hao, Z. Shi, N. Zhao, Y. Wang, Bioact. Mater. 12(2022) 120-132.
[28] X. Yao, R. Peng, J. Ding, Adv. Mater. 25(2013) 5257-5286.
[29] X. Sun, X. Li, H. Qi, X. Hou, J. Zhao, X. Yuan, X. Ma, J. Orthop. Transl. 24(2020) 76-87.
[30] G.A. Rico-Llanos, S. Borrego-González, M. Moncayo-Donoso, J. Becerra, R. Visser, Polymers 13 (2021) 599.
[31] C. Dai, H. Guo, J. Lu, J. Shi, J. Wei, C. Liu, Biomaterials 32 (2011) 8506-8517.
[32] H.J. Kim, W.J. Kim, H.M. Ryoo, Mol. Cells 3 (2020) 160-167.
[33] A. Guasto, V. Cormier-Daire, Int. J. Mol. Sci. 22(2021) 4321.
[34] X. Shi, Y. Wang, R.R. Varshney, L. Ren, F. Zhang, D.A. Wang, Biomaterials 30 (20 09) 3996-40 05.
[35] J. Karar, A. Maity, Front. Molec. Neurosci. 4(2011) 51-59.
[36] F. Liu, X. Huang, Z. Luo, J. He, F. Haider, C. Song, L. Peng, T. Chen, B. Wu, Ox- idative Med. Cell. Longev. 2019 (2019) 6595189.
[37] T. Kokubo, H. Takadama, Biomaterials 27 (2006) 2907-2915.
[38] C. Wang, Y. Xue, K. Lin, J. Lu, J. Chang, J. Sun, Acta Biomater 8 (2012) 350-360.
[39] C.B. Ching, D.E. Hansel, Lab. Invest. 90(2010) 1406-1614.

Biomimetic hydroxyapatite coating on the 3D-printed bioactive porous composite ceramic scaffolds promoted osteogenic differentiation via PI3K/AKT/mTOR signaling pathways and facilitated bone regeneration in vivo

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