Osteoimmunomodulatory effects of inorganic biomaterials in the process of bone repair_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

XING Fei ¹ , WU Qiyou ² , ZHE Man ³ , LUO Rong ¹ , XIANG Zhou ¹ ,  LIU Ming ¹

1. Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;
2. West China School of Medicine, Sichuan University, Chengdu Sichuan, 610041, P. R. China;
3. Animal Experiment Center, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P. R. China;

Corresponding author：

LIU Ming, Email: liuming15@qq.com

Keywords：

Inorganic biomaterial; macrophages; immunomodulation; osteoimmune; bone repair

DOI：

10.7507/1002-1892.202112025

Video：

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Objective To review the osteoimmunomodulatory effects and related mechanisms of inorganic biomaterials in the process of bone repair. Methods A wide range of relevant domestic and foreign literature was reviewed, the characteristics of various inorganic biomaterials in the process of bone repair were summarized, and the osteoimmunomodulatory mechanism in the process of bone repair was discussed. Results Immune cells play a very important role in the dynamic balance of bone tissue. Inorganic biomaterials can directly regulate the immune cells in the body by changing their surface roughness, surface wettability, and other physical and chemical properties, constructing a suitable immune microenvironment, and then realizing dynamic regulation of bone repair. Conclusion Inorganic biomaterials are a class of biomaterials that are widely used in bone repair. Fully understanding the role of inorganic biomaterials in immunomodulation during bone repair will help to design novel bone immunomodulatory scaffolds for bone repair.

Citation： XING Fei, WU Qiyou, ZHE Man, LUO Rong, XIANG Zhou, LIU Ming. Osteoimmunomodulatory effects of inorganic biomaterials in the process of bone repair. Chinese Journal of Reparative and Reconstructive Surgery, 2022, 36(4): 517-522. doi: 10.7507/1002-1892.202112025 Copy

1.	Bittner SM, Smith BT, Diaz-Gomez L, et al. Fabrication and mechanical characterization of 3D printed vertical uniform and gradient scaffolds for bone and osteochondral tissue engineering. Acta Biomater, 2019, 90: 37-48.
2.	Bacakova L, Filova E, Parizek M, et al. Modulation of cell adhesion, proliferation and differentiation on materials designed for body implants. Biotechnol Adv, 2011, 29(6): 739-767.
3.	Kim HD, Amirthalingam S, Kim SL, et al. Biomimetic materials and fabrication approaches for bone tissue engineering. Adv Healthc Mater, 2017, 6(23): 1700612. doi: 10.1002/adhm.201700612.
4.	Humbert P, Brennan MÁ, Davison N, et al. Immune modulation by transplanted calcium phosphate biomaterials and human mesenchymal stromal cells in bone regeneration. Front Immunol, 2019, 10: 663. doi: 10.3389/fimmu.2019.00663.
5.	Walsh MC, Takegahara N, Kim H, et al. Updating osteoimmunology: regulation of bone cells by innate and adaptive immunity. Nat Rev Rheumatol, 2018, 14(3): 146-156.
6.	Xing F, Xiang Z, Rommens PM, et al. 3D bioprinting for vascularized tissue-engineered bone fabrication. Materials (Basel), 2020, 13(10): 2278. doi: 10.3390/ma13102278.
7.	Abaricia JO, Shah AH, Chaubal M, et al. Wnt signaling modulates macrophage polarization and is regulated by biomaterial surface properties. Biomaterials, 2020, 243: 119920. doi: 10.1016/j.biomaterials.2020.119920.
8.	Betz VM, Betz OB, Harris MB, et al. Bone tissue engineering and repair by gene therapy. Front Biosci, 2008, 13: 833-841.
9.	Albrektsson T, Johansson C. Osteoinduction, osteoconduction and osseointegration. Eur Spine J, 2001, Suppl 2: S96-S101.
10.	Habibovic P, Barralet JE. Bioinorganics and biomaterials: bone repair. Acta Biomater, 2011, 7(8): 3013-3026.
11.	Skaggs H, Chellman GJ, Collinge M, et al. Comparison of immune system development in nonclinical species and humans: Closing information gaps for immunotoxicity testing and human translatability. Reprod Toxicol, 2019, 89: 178-188.
12.	Chang MK, Raggatt LJ, Alexander KA, et al. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol, 2008, 181(2): 1232-1244.
13.	Xing F, Li L, Zhou C, et al. Regulation and directing stem cell fate by tissue engineering functional microenvironments: Scaffold physical and chemical cues. Stem Cells Int, 2019, 2019: 2180925. doi: 10.1155/2019/2180925.
14.	Chen Z, Mao X, Tan L, et al. Osteoimmunomodulatory properties of magnesium scaffolds coated with β-tricalcium phosphate. Biomaterials, 2014, 35(30): 8553-8565.
15.	Claes L, Recknagel S, Ignatius A. Fracture healing under healthy and inflammatory conditions. Nat Rev Rheumatol, 2012, 8(3): 133-143.
16.	Sadowska JM, Ginebra MP. Inflammation and biomaterials: role of the immune response in bone regeneration by inorganic scaffolds. J Mater Chem B, 2020, 8(41): 9404-9427.
17.	Hotchkiss KM, Reddy GB, Hyzy SL, et al. Titanium surface characteristics, including topography and wettability, alter macrophage activation. Acta Biomater, 2016, 31: 425-434.
18.	Laschke MW, Harder Y, Amon M, et al. Angiogenesis in tissue engineering: breathing life into constructed tissue substitutes. Tissue Eng, 2006, 12(8): 2093-2104.
19.	Wu AC, Raggatt LJ, Alexander KA, et al. Unraveling macrophage contributions to bone repair. Bonekey Rep, 2013, 2: 373. doi: 10.1038/bonekey.2013.107.
20.	Negrescu AM, Cimpean A. The state of the art and prospects for osteoimmunomodulatory biomaterials. Materials (Basel), 2021, 14(6): 1357. doi: 10.3390/ma14061357.
21.	Klinge U, Klosterhalfen B, Birkenhauer V, et al. Impact of polymer pore size on the interface scar formation in a rat model. J Surg Res, 2002, 103(2): 208-214.
22.	Han Q, Wang C, Chen H, et al. Porous tantalum and titanium in orthopedics: A review. ACS Biomater Sci Eng, 2019, 5(11): 5798-5824.
23.	Zhu Y, Zhang K, Zhao R, et al. Bone regeneration with micro/nano hybrid-structured biphasic calcium phosphate bioceramics at segmental bone defect and the induced immunoregulation of MSCs. Biomaterials, 2017, 147: 133-144.
24.	Dobbenga S, Fratila-Apachitei LE, Zadpoor AA. Nanopattern-induced osteogenic differentiation of stem cells—A systematic review. Acta Biomater, 2016, 46: 3-14.
25.	Chen Z, Bachhuka A, Wei F, et al. Nanotopography-based strategy for the precise manipulation of osteoimmunomodulation in bone regeneration. Nanoscale, 2017, 9(46): 18129-18152.
26.	Yang C, Zhao C, Wang X, et al. Stimulation of osteogenesis and angiogenesis by micro/nano hierarchical hydroxyapatite via macrophage immunomodulation. Nanoscale, 2019, 11(38): 17699-17708.
27.	Neacsu P, Mazare A, Schmuki P, et al. Attenuation of the macrophage inflammatory activity by TiO₂ nanotubes via inhibition of MAPK and NF-κB pathways. Int J Nanomedicine, 2015, 10: 6455-6467.
28.	Chen M, Zhang Y, Zhou P, et al. Substrate stiffness modulates bone marrow-derived macrophage polarization through NF-κB signaling pathway. Bioact Mater, 2020, 5(4): 880-890.
29.	Zhang J, Luo X, Barbieri D, et al. The size of surface microstructures as an osteogenic factor in calcium phosphate ceramics. Acta Biomater, 2014, 10(7): 3254-3263.
30.	Davison NL, Su J, Yuan H, et al. Influence of surface microstructure and chemistry on osteoinduction and osteoclastogenesis by biphasic calcium phosphate discs. Eur Cell Mater, 2015, 29: 314-329.
31.	Li M, Guo X, Qi W, et al. Macrophage polarization plays roles in bone formation instructed by calcium phosphate ceramics. J Mater Chem B, 2020, 8(9): 1863-1877.
32.	Chen Z, Bachhuka A, Han S, et al. Tuning chemistry and topography of nanoengineered surfaces to manipulate immune response for bone regeneration applications. ACS Nano, 2017, 11(5): 4494-4506.
33.	Xie Y, Hu C, Feng Y, et al. Osteoimmunomodulatory effects of biomaterial modification strategies on macrophage polarization and bone regeneration. Regen Biomater, 2020, 7(3): 233-245.
34.	Vishwakarma A, Bhise NS, Evangelista MB, et al. Engineering immunomodulatory biomaterials to tune the inflammatory response. Trends Biotechnol, 2016, 34(6): 470-482.
35.	Kakizawa Y, Lee JS, Bell B, et al. Precise manipulation of biophysical particle parameters enables control of proinflammatory cytokine production in presence of TLR 3 and 4 ligands. Acta Biomater, 2017, 57: 136-145.
36.	Li G, Yang P, Guo X, et al. An in vitro evaluation of inflammation response of titanium functionalized with heparin/fibronectin complex. Cytokine, 2011, 56(2): 208-217.
37.	Bartneck M, Keul HA, Singh S, et al. Rapid uptake of gold nanorods by primary human blood phagocytes and immunomodulatory effects of surface chemistry. ACS Nano, 2010, 4(6): 3073-3086.
38.	Neumann S, Burkert K, Kemp R, et al. Activation of the NLRP3 inflammasome is not a feature of all particulate vaccine adjuvants. Immunol Cell Biol, 2014, 92(6): 535-542.
39.	Kamath S, Bhattacharyya D, Padukudru C, et al. Surface chemistry influences implant-mediated host tissue responses. J Biomed Mater Res A, 2008, 86(3): 617-626.
40.	Barbosa JN, Barbosa MA, Aguas AP. Inflammatory responses and cell adhesion to self-assembled monolayers of alkanethiolates on gold. Biomaterials, 2004, 25(13): 2557-2563.
41.	Keselowsky BG, Collard DM, García AJ. Surface chemistry modulates focal adhesion composition and signaling through changes in integrin binding. Biomaterials, 2004, 25(28): 5947-5954.
42.	Hung CJ, Kao CT, Chen YJ, et al. Antiosteoclastogenic activity of silicate-based materials antagonizing receptor activator for nuclear factor kappaB ligand-induced osteoclast differentiation of murine marcophages. J Endod, 2013, 39(12): 1557-1561.
43.	Chen X, Wang M, Chen F, et al. Correlations between macrophage polarization and osteoinduction of porous calcium phosphate ceramics. Acta Biomater, 2020, 103: 318-332.
44.	Shiwaku Y, Neff L, Nagano K, et al. The crosstalk between osteoclasts and osteoblasts is dependent upon the composition and structure of biphasic calcium phosphates. PLoS One, 2015, 10(7): e0132903. doi: 10.1371/journal.pone.0132903.
45.	Li T, Peng M, Yang Z, et al. 3D-printed IFN-γ-loading calcium silicate-β-tricalcium phosphate scaffold sequentially activates M1 and M2 polarization of macrophages to promote vascularization of tissue engineering bone. Acta Biomater, 2018, 71: 96-107.
46.	Mansour A, Abu-Nada L, Al-Waeli H, et al. Bone extracts immunomodulate and enhance the regenerative performance of dicalcium phosphates bioceramics. Acta Biomater, 2019, 89: 343-358.

1. Bittner SM, Smith BT, Diaz-Gomez L, et al. Fabrication and mechanical characterization of 3D printed vertical uniform and gradient scaffolds for bone and osteochondral tissue engineering. Acta Biomater, 2019, 90: 37-48.
2. Bacakova L, Filova E, Parizek M, et al. Modulation of cell adhesion, proliferation and differentiation on materials designed for body implants. Biotechnol Adv, 2011, 29(6): 739-767.
3. Kim HD, Amirthalingam S, Kim SL, et al. Biomimetic materials and fabrication approaches for bone tissue engineering. Adv Healthc Mater, 2017, 6(23): 1700612. doi: 10.1002/adhm.201700612.
4. Humbert P, Brennan MÁ, Davison N, et al. Immune modulation by transplanted calcium phosphate biomaterials and human mesenchymal stromal cells in bone regeneration. Front Immunol, 2019, 10: 663. doi: 10.3389/fimmu.2019.00663.
5. Walsh MC, Takegahara N, Kim H, et al. Updating osteoimmunology: regulation of bone cells by innate and adaptive immunity. Nat Rev Rheumatol, 2018, 14(3): 146-156.
6. Xing F, Xiang Z, Rommens PM, et al. 3D bioprinting for vascularized tissue-engineered bone fabrication. Materials (Basel), 2020, 13(10): 2278. doi: 10.3390/ma13102278.
7. Abaricia JO, Shah AH, Chaubal M, et al. Wnt signaling modulates macrophage polarization and is regulated by biomaterial surface properties. Biomaterials, 2020, 243: 119920. doi: 10.1016/j.biomaterials.2020.119920.
8. Betz VM, Betz OB, Harris MB, et al. Bone tissue engineering and repair by gene therapy. Front Biosci, 2008, 13: 833-841.
9. Albrektsson T, Johansson C. Osteoinduction, osteoconduction and osseointegration. Eur Spine J, 2001, Suppl 2: S96-S101.
10. Habibovic P, Barralet JE. Bioinorganics and biomaterials: bone repair. Acta Biomater, 2011, 7(8): 3013-3026.
11. Skaggs H, Chellman GJ, Collinge M, et al. Comparison of immune system development in nonclinical species and humans: Closing information gaps for immunotoxicity testing and human translatability. Reprod Toxicol, 2019, 89: 178-188.
12. Chang MK, Raggatt LJ, Alexander KA, et al. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo. J Immunol, 2008, 181(2): 1232-1244.
13. Xing F, Li L, Zhou C, et al. Regulation and directing stem cell fate by tissue engineering functional microenvironments: Scaffold physical and chemical cues. Stem Cells Int, 2019, 2019: 2180925. doi: 10.1155/2019/2180925.
14. Chen Z, Mao X, Tan L, et al. Osteoimmunomodulatory properties of magnesium scaffolds coated with β-tricalcium phosphate. Biomaterials, 2014, 35(30): 8553-8565.
15. Claes L, Recknagel S, Ignatius A. Fracture healing under healthy and inflammatory conditions. Nat Rev Rheumatol, 2012, 8(3): 133-143.
16. Sadowska JM, Ginebra MP. Inflammation and biomaterials: role of the immune response in bone regeneration by inorganic scaffolds. J Mater Chem B, 2020, 8(41): 9404-9427.
17. Hotchkiss KM, Reddy GB, Hyzy SL, et al. Titanium surface characteristics, including topography and wettability, alter macrophage activation. Acta Biomater, 2016, 31: 425-434.
18. Laschke MW, Harder Y, Amon M, et al. Angiogenesis in tissue engineering: breathing life into constructed tissue substitutes. Tissue Eng, 2006, 12(8): 2093-2104.
19. Wu AC, Raggatt LJ, Alexander KA, et al. Unraveling macrophage contributions to bone repair. Bonekey Rep, 2013, 2: 373. doi: 10.1038/bonekey.2013.107.
20. Negrescu AM, Cimpean A. The state of the art and prospects for osteoimmunomodulatory biomaterials. Materials (Basel), 2021, 14(6): 1357. doi: 10.3390/ma14061357.
21. Klinge U, Klosterhalfen B, Birkenhauer V, et al. Impact of polymer pore size on the interface scar formation in a rat model. J Surg Res, 2002, 103(2): 208-214.
22. Han Q, Wang C, Chen H, et al. Porous tantalum and titanium in orthopedics: A review. ACS Biomater Sci Eng, 2019, 5(11): 5798-5824.
23. Zhu Y, Zhang K, Zhao R, et al. Bone regeneration with micro/nano hybrid-structured biphasic calcium phosphate bioceramics at segmental bone defect and the induced immunoregulation of MSCs. Biomaterials, 2017, 147: 133-144.
24. Dobbenga S, Fratila-Apachitei LE, Zadpoor AA. Nanopattern-induced osteogenic differentiation of stem cells—A systematic review. Acta Biomater, 2016, 46: 3-14.
25. Chen Z, Bachhuka A, Wei F, et al. Nanotopography-based strategy for the precise manipulation of osteoimmunomodulation in bone regeneration. Nanoscale, 2017, 9(46): 18129-18152.
26. Yang C, Zhao C, Wang X, et al. Stimulation of osteogenesis and angiogenesis by micro/nano hierarchical hydroxyapatite via macrophage immunomodulation. Nanoscale, 2019, 11(38): 17699-17708.
27. Neacsu P, Mazare A, Schmuki P, et al. Attenuation of the macrophage inflammatory activity by TiO₂ nanotubes via inhibition of MAPK and NF-κB pathways. Int J Nanomedicine, 2015, 10: 6455-6467.
28. Chen M, Zhang Y, Zhou P, et al. Substrate stiffness modulates bone marrow-derived macrophage polarization through NF-κB signaling pathway. Bioact Mater, 2020, 5(4): 880-890.
29. Zhang J, Luo X, Barbieri D, et al. The size of surface microstructures as an osteogenic factor in calcium phosphate ceramics. Acta Biomater, 2014, 10(7): 3254-3263.
30. Davison NL, Su J, Yuan H, et al. Influence of surface microstructure and chemistry on osteoinduction and osteoclastogenesis by biphasic calcium phosphate discs. Eur Cell Mater, 2015, 29: 314-329.
31. Li M, Guo X, Qi W, et al. Macrophage polarization plays roles in bone formation instructed by calcium phosphate ceramics. J Mater Chem B, 2020, 8(9): 1863-1877.
32. Chen Z, Bachhuka A, Han S, et al. Tuning chemistry and topography of nanoengineered surfaces to manipulate immune response for bone regeneration applications. ACS Nano, 2017, 11(5): 4494-4506.
33. Xie Y, Hu C, Feng Y, et al. Osteoimmunomodulatory effects of biomaterial modification strategies on macrophage polarization and bone regeneration. Regen Biomater, 2020, 7(3): 233-245.
34. Vishwakarma A, Bhise NS, Evangelista MB, et al. Engineering immunomodulatory biomaterials to tune the inflammatory response. Trends Biotechnol, 2016, 34(6): 470-482.
35. Kakizawa Y, Lee JS, Bell B, et al. Precise manipulation of biophysical particle parameters enables control of proinflammatory cytokine production in presence of TLR 3 and 4 ligands. Acta Biomater, 2017, 57: 136-145.
36. Li G, Yang P, Guo X, et al. An in vitro evaluation of inflammation response of titanium functionalized with heparin/fibronectin complex. Cytokine, 2011, 56(2): 208-217.
37. Bartneck M, Keul HA, Singh S, et al. Rapid uptake of gold nanorods by primary human blood phagocytes and immunomodulatory effects of surface chemistry. ACS Nano, 2010, 4(6): 3073-3086.
38. Neumann S, Burkert K, Kemp R, et al. Activation of the NLRP3 inflammasome is not a feature of all particulate vaccine adjuvants. Immunol Cell Biol, 2014, 92(6): 535-542.
39. Kamath S, Bhattacharyya D, Padukudru C, et al. Surface chemistry influences implant-mediated host tissue responses. J Biomed Mater Res A, 2008, 86(3): 617-626.
40. Barbosa JN, Barbosa MA, Aguas AP. Inflammatory responses and cell adhesion to self-assembled monolayers of alkanethiolates on gold. Biomaterials, 2004, 25(13): 2557-2563.
41. Keselowsky BG, Collard DM, García AJ. Surface chemistry modulates focal adhesion composition and signaling through changes in integrin binding. Biomaterials, 2004, 25(28): 5947-5954.
42. Hung CJ, Kao CT, Chen YJ, et al. Antiosteoclastogenic activity of silicate-based materials antagonizing receptor activator for nuclear factor kappaB ligand-induced osteoclast differentiation of murine marcophages. J Endod, 2013, 39(12): 1557-1561.
43. Chen X, Wang M, Chen F, et al. Correlations between macrophage polarization and osteoinduction of porous calcium phosphate ceramics. Acta Biomater, 2020, 103: 318-332.
44. Shiwaku Y, Neff L, Nagano K, et al. The crosstalk between osteoclasts and osteoblasts is dependent upon the composition and structure of biphasic calcium phosphates. PLoS One, 2015, 10(7): e0132903. doi: 10.1371/journal.pone.0132903.
45. Li T, Peng M, Yang Z, et al. 3D-printed IFN-γ-loading calcium silicate-β-tricalcium phosphate scaffold sequentially activates M1 and M2 polarization of macrophages to promote vascularization of tissue engineering bone. Acta Biomater, 2018, 71: 96-107.
46. Mansour A, Abu-Nada L, Al-Waeli H, et al. Bone extracts immunomodulate and enhance the regenerative performance of dicalcium phosphates bioceramics. Acta Biomater, 2019, 89: 343-358.

Chinese Journal of Reparative and Reconstructive Surgery

Osteoimmunomodulatory effects of inorganic biomaterials in the process of bone repair

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