Research progress on strontium modified β-tricalcium phosphate composite biomaterials with immune regulatory properties_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

LI Huanxi ^1,2 , SHAN Xingyu ² , WANG Hongda ² , TIAN Zhimin ² , HE Chunnuo ² ,  ZHANG Haoqiang ¹

1. Department of Joint Surgery, the 940th Hospital of Chinese PLA Joint Logistics Support Force, Lanzhou Gansu, 730000, P. R. China;
2. The First Clinical College of Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou Gansu, 730000, P. R. China;

Corresponding author：

ZHANG Haoqiang, Email: zhanghaoqiang_fmmu@163.com

Keywords：

Bone repair; β-tricalcium phosphate; strontium; immune regulation

DOI：

10.7507/1002-1892.202502063

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the research progress of strontium (Sr) modified β-tricalcium phosphate composite biomaterials (SrTCP) promoting osteogenesis through immune regulation, and provides reference and theoretical support for the further development and research of SrTCP bone repair materials in bone tissue engineering in the future. Methods The literature about SrTCP promoting osteogenesis through immune regulation at home and abroad in recent years was extensively reviewed, and the preparation methods, immune mechanism and application of promoting osteogenesis were summarized and analyzed. Results The preparation methods of SrTCP include solid-state reaction sintering method, solution combustion quenching method, direct doping method, ion substitution method, etc. SrTCP has immune regulatory effects, which can play an immune regulatory role in inducing macrophage polarization, inducing angiogenesis and anti oxidative stress to promote osteogenesis. Conclusion At present, studies have shown that SrTCP can promote bone defect repair through immune regulation. Subsequent studies can start from the control of the optimal repair concentration and release rate of Sr, and further clarify the specific mechanism of SrTCP in promoting angiogenesis and anti oxidative stress, which is helpful to develop new materials for bone defect repair.

Citation： LI Huanxi, SHAN Xingyu, WANG Hongda, TIAN Zhimin, HE Chunnuo, ZHANG Haoqiang. Research progress on strontium modified β-tricalcium phosphate composite biomaterials with immune regulatory properties. Chinese Journal of Reparative and Reconstructive Surgery, 2025, 39(4): 511-517. doi: 10.7507/1002-1892.202502063 Copy

1.	Dei Rossi G, Vergani LM, Buccino F. A novel triad of bio-inspired design, digital fabrication, and bio-derived materials for personalised bone repair. Materials (Basel), 2024, 17(21): 5305. doi: 10.3390/ma17215305.
2.	Ge C, Chen F, Mao L, et al. Strontium ranelate-loaded POFC/β-TCP porous scaffolds for osteoporotic bone repair. RSC Adv, 2020, 10(15): 9016-9025.
3.	Takase K, Niikura T, Fukui T, et al. Three-dimensional printed calcium phosphate scaffolds emulate bone microstructure to promote bone regrowth and repair. J Mater Sci Mater Med, 2024, 35(1): 53. doi: 10.1007/s10856-024-06817-8.
4.	沈永帅, 刘欣春. 可降解材料在骨科临床中的应用. 中国材料进展, 2017, 36(3): 231-235.
5.	Tovar N, Witek L, Atria P, et al. Form and functional repair of long bone using 3D-printed bioactive scaffolds. J Tissue Eng Regen Med, 2018, 12(9): 1986-1999.
6.	Sun T, Feng Z, He W, et al. Novel 3D-printing bilayer GelMA-based hydrogel containing BP, β-TCP and exosomes for cartilage-bone integrated repair. Biofabrication, 2023, 16(1). doi: 10.1088/1758-5090/ad04fe.
7.	Dang AT, Ono M, Wang Z, et al. Local E-rhBMP-2/β-TCP application rescues osteocyte dendritic integrity and reduces microstructural damage in alveolar bone post-extraction in MRONJ-like mouse model. Int J Mol Sci, 2024, 25(12): 6648. doi: 10.3390/ijms25126648.
8.	单宇华, 陈振琦. β-磷酸三钙骨免疫学特性的研究进展. 口腔医学研究, 2021, 37(9): 787-790.
9.	Clézardin P, Coleman R, Puppo M, et al. Bone metastasis: mechanisms, therapies, and biomarkers. Physiol Rev, 2021, 101(3): 797-855.
10.	Miao Q, Yang X, Diao J, et al. 3D printed strontium-doped calcium phosphate ceramic scaffold enhances early angiogenesis and promotes bone repair through the regulation of macrophage polarization. Mater Today Bio, 2023, 23: 100871. doi: 10.1016/j.mtbio.2023.100871.
11.	Trindade R, Albrektsson T, Tengvall P, et al. Foreign body reaction to biomaterials: On mechanisms for buildup and breakdown of osseointegration. Clin Implant Dent Relat Res, 2016, 18(1): 192-203.
12.	Wu H, Chen C, Li J, et al. Engineered magneto-piezoelectric nanoparticles-enhanced scaffolds disrupt biofilms and activate oxidative phosphorylation in Icam1+ macrophages for infectious bone defect regeneration. ACS Nano, 2024, 18(52): 35575-35594.
13.	Gou M, Wang H, Xie H, et al. Macrophages in guided bone regeneration: potential roles and future directions. Front Immunol, 2024, 15: 1396759. doi: 10.3389/fimmu.2024.1396759.
14.	Li Y, Yao L, Zhang C, et al. Growth hormone-releasing peptide 2 may be associated with decreased M1 macrophage production and increased histologic and biomechanical tendon-bone healing properties in a rat rotator cuff tear model. Arthroscopy, 2024. doi: 10.1016/j.arthro.2024.11.094.
15.	Kim DY, Ryu JH, Kim JH, et al. Targeting age-related impaired bone healing: ZnO nanoparticle-infused composite fibers modulate excessive NETosis and prolonged inflammation in aging. Int J Mol Sci, 2024, 25(23): 12851. doi: 10.3390/ijms252312851.
16.	Xiong Y, Lin Z, Bu P, et al. A whole-course-repair system based on neurogenesis-angiogenesis crosstalk and macrophage reprogramming promotes diabetic wound healing. Adv Mater, 2023, 35(19): e2212300. doi: 10.1002/adma.202212300.
17.	Li XR, Deng QS, He SH, et al. 3D cryo-printed hierarchical porous scaffolds provide immobilization of surface-functionalized sleep-inspired small extracellular vesicles: synergistic therapeutic strategies for vascularized bone regeneration based on macrophage phenotype modulation and angiogenesis-osteogenesis coupling. J Nanobiotechnology, 2024, 22(1): 764. doi: 10.1186/s12951-024-02977-5.
18.	You J, Zhang Y, Zhou Y. Strontium functionalized in biomaterials for bone tissue engineering: A prominent role in osteoimmunomodulation. Front Bioeng Biotechnol, 2022, 10: 928799. doi: 10.3389/fbioe.2022.928799.
19.	Miao Q, Jiang N, Yang Q, et al. Multi-stage controllable degradation of strontium-doped calcium sulfate hemihydrate-tricalcium phosphate microsphere composite as a substitute for osteoporotic bone defect repairing: degradation behavior and bone response. Biomed Mater, 2021, 17(1). doi: 10.1088/1748-605X/ac4323.
20.	He F, Lu T, Fang X, et al. Study on MgxSr₃-x(PO4)r₂ bioceramics as potential bone grafts. Colloids Surf B Biointerfaces, 2019, 175: 158-165.
21.	Safarova Yantsen Y, Nessipbekova A, Syzdykova A, et al. Strontium- and copper-doped ceramic granules in bone regeneration-associated cellular processes. J Funct Biomater, 2024, 15(11): 352. doi: 10.3390/jfb15110352.
22.	Deng L, Huang L, Pan H, et al. 3D printed strontium-zinc-phosphate bioceramic scaffolds with multiple biological functions for bone tissue regeneration. J Mater Chem B, 2023, 11(24): 5469-5482.
23.	Tian Y, Lu T, He F, et al. β-tricalcium phosphate composite ceramics with high compressive strength, enhanced osteogenesis and inhibited osteoclastic activities. Colloids Surf B Biointerfaces, 2018, 167: 318-327.
24.	Goodarzi H, Hashemi-Najafabadi S, Baheiraei N, et al. Preparation and characterization of nanocomposite scaffolds (collagen/β-TCP/SrO) for bone tissue engineering. Tissue Eng Regen Med, 2019, 16(3): 237-251.
25.	Tarafder S, Dernell WS, Bandyopadhyay A, et al. SrO- and MgO-doped microwave sintered 3D printed tricalcium phosphate scaffolds: mechanical properties and in vivo osteogenesis in a rabbit model. J Biomed Mater Res B Appl Biomater, 2015, 103(3): 679-690.
26.	Asensio G, Benito-Garzón L, Ramírez-Jiménez RA, et al. Biomimetic gradient scaffolds containing hyaluronic acid and Sr/Zn folates for osteochondral tissue engineering. Polymers (Basel), 2021, 14(1): 12. doi: 10.3390/polym14010012.
27.	Bootchanont A, Chaosuan N, Promdee S, et al. Correlation between biomedical and structural properties of Zn/Sr modified calcium phosphates. Biometals, 2024, 37(5): 1177-1189.
28.	Chen F, Tian L, Pu X, et al. Enhanced ectopic bone formation by strontium-substituted calcium phosphate ceramics through regulation of osteoclastogenesis and osteoblastogenesis. Biomater Sci, 2022, 10(20): 5925-5937.
29.	Sugimoto H, Inagaki Y, Furukawa A, et al. Silicate/zinc-substituted strontium apatite coating improves the osteoinductive properties of β-tricalcium phosphate bone graft substitute. BMC Musculoskelet Disord, 2021, 22(1): 673. doi: 10.1186/s12891-021-04563-4.
30.	Pang B, Xian J, Chen J, et al. Cuttlefish bone-derived calcium phosphate bioceramics have enhanced osteogenic properties. J Funct Biomater, 2024, 15(8): 212. doi: 10.3390/jfb15080212.
31.	Basu S, Ghosh A, Barui A, et al. Epithelial cell functionality on electroconductive Fe/Sr co-doped biphasic calcium phosphate. J Biomater Appl, 2019, 33(8): 1035-1052.
32.	Huang B, Li S, Dai S, et al. Ti₃C2Tx MXene-decorated 3D-printed ceramic scaffolds for Enhancing osteogenesis by spatiotemporally orchestrating inflammatory and bone repair responses. Adv Sci (Weinh), 2024, 11(34): e2400229. doi: 10.1002/advs.202400229.
33.	Singh SS, Roy A, Lee B, et al. Study of hMSC proliferation and differentiation on Mg and Mg-Sr containing biphasic β-tricalcium phosphate and amorphous calcium phosphate ceramics. Mater Sci Eng C Mater Biol Appl, 2016, 64: 219-228.
34.	Arbez B, Manero F, Mabilleau G, et al. Human macrophages and osteoclasts resorb β-tricalcium phosphate in vitro but not mouse macrophages. Micron, 2019, 125: 102730. doi: 10.1016/j.micron.2019.102730.
35.	Chazono M, Tanaka T, Kitasato S, et al. Electron microscopic study on bone formation and bioresorption after implantation of beta-tricalcium phosphate in rabbit models. J Orthop Sci, 2008, 13(6): 550-555.
36.	Che J, Sun T, Lv X, et al. Influence of Ag and/or Sr dopants on the mechanical properties and in vitro degradation of β-tricalcium phosphate-based ceramics. materials (basel). 2023, 16(17): 6025. doi: 10.3390/ma16176025.
37.	Bohner M, Santoni BLG, Döbelin N. β-tricalcium phosphate for bone substitution: Synthesis and properties. Acta Biomater, 2020, 113: 23-41.
38.	Naruphontjirakul P, Li S, Pinna A, et al. Interaction of monodispersed strontium containing bioactive glass nanoparticles with macrophages. Biomater Adv, 2022, 133: 112610. doi: 10.1016/j.msec.2021.112610.
39.	Yu D, Guo S, Yu M, et al. Immunomodulation and osseointegration activities of Na₂TiO₃ nanorods-arrayed coatings doped with different Sr content. Bioact Mater, 2021, 10: 323-334.
40.	Jiang S, Wang X, Ma Y, et al. Synergistic effect of micro-nano-hybrid surfaces and Sr doping on the osteogenic and angiogenic capacity of hydroxyapatite bioceramics scaffolds. Int J Nanomedicine, 2022, 17: 783-797.
41.	Miao A, Li Q, Tang G, et al. Alginate-containing 3D-printed hydrogel scaffolds incorporated with strontium promotes vascularization and bone regeneration. Int J Biol Macromol, 2024, 273(Pt 1): 133038. doi: 10.1016/j.ijbiomac.2024.133038.
42.	Li S, Zhang L, Liu C, et al. Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects. Bioact Mater, 2022, 23: 101-117.
43.	Sha W, Zhao B, Wei H, et al. Astragalus polysaccharide ameliorates vascular endothelial dysfunction by stimulating macrophage M2 polarization via potentiating Nrf2/HO-1 signaling pathway. Phytomedicine, 2023, 112: 154667. doi: 10.1016/j.phymed.2023.154667.
44.	Jomova K, Raptova R, Alomar SY, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol, 2023, 97(10): 2499-2574.
45.	Zhou C, Chen YQ, Zhu YH, et al. Antiadipogenesis and osseointegration of strontium-doped implant surfaces. J Dent Res, 2019, 98(7): 795-802.
46.	Li Y, Chen M, Yan J, et al. Tannic acid/Sr²⁺-coated silk/graphene oxide-based meniscus scaffold with anti-inflammatory and anti-ROS functions for cartilage protection and delaying osteoarthritis. Acta Biomater, 2021, 126: 119-131.
47.	Asensio G, Martín-Del-Campo M, Ramírez RA, et al. New insights into the in vitro antioxidant routes and osteogenic properties of Sr/Zn phytate compounds. Pharmaceutics, 2023, 15(2): 339. doi: 10.3390/pharmaceutics15020339.
48.	Wu X, Tang Z, Wu K, et al. Strontium-calcium phosphate hybrid cement with enhanced osteogenic and angiogenic properties for vascularised bone regeneration. J Mater Chem B, 2021, 9(30): 5982-5997.

1. Dei Rossi G, Vergani LM, Buccino F. A novel triad of bio-inspired design, digital fabrication, and bio-derived materials for personalised bone repair. Materials (Basel), 2024, 17(21): 5305. doi: 10.3390/ma17215305.
2. Ge C, Chen F, Mao L, et al. Strontium ranelate-loaded POFC/β-TCP porous scaffolds for osteoporotic bone repair. RSC Adv, 2020, 10(15): 9016-9025.
3. Takase K, Niikura T, Fukui T, et al. Three-dimensional printed calcium phosphate scaffolds emulate bone microstructure to promote bone regrowth and repair. J Mater Sci Mater Med, 2024, 35(1): 53. doi: 10.1007/s10856-024-06817-8.
4. 沈永帅, 刘欣春. 可降解材料在骨科临床中的应用. 中国材料进展, 2017, 36(3): 231-235.
5. Tovar N, Witek L, Atria P, et al. Form and functional repair of long bone using 3D-printed bioactive scaffolds. J Tissue Eng Regen Med, 2018, 12(9): 1986-1999.
6. Sun T, Feng Z, He W, et al. Novel 3D-printing bilayer GelMA-based hydrogel containing BP, β-TCP and exosomes for cartilage-bone integrated repair. Biofabrication, 2023, 16(1). doi: 10.1088/1758-5090/ad04fe.
7. Dang AT, Ono M, Wang Z, et al. Local E-rhBMP-2/β-TCP application rescues osteocyte dendritic integrity and reduces microstructural damage in alveolar bone post-extraction in MRONJ-like mouse model. Int J Mol Sci, 2024, 25(12): 6648. doi: 10.3390/ijms25126648.
8. 单宇华, 陈振琦. β-磷酸三钙骨免疫学特性的研究进展. 口腔医学研究, 2021, 37(9): 787-790.
9. Clézardin P, Coleman R, Puppo M, et al. Bone metastasis: mechanisms, therapies, and biomarkers. Physiol Rev, 2021, 101(3): 797-855.
10. Miao Q, Yang X, Diao J, et al. 3D printed strontium-doped calcium phosphate ceramic scaffold enhances early angiogenesis and promotes bone repair through the regulation of macrophage polarization. Mater Today Bio, 2023, 23: 100871. doi: 10.1016/j.mtbio.2023.100871.
11. Trindade R, Albrektsson T, Tengvall P, et al. Foreign body reaction to biomaterials: On mechanisms for buildup and breakdown of osseointegration. Clin Implant Dent Relat Res, 2016, 18(1): 192-203.
12. Wu H, Chen C, Li J, et al. Engineered magneto-piezoelectric nanoparticles-enhanced scaffolds disrupt biofilms and activate oxidative phosphorylation in Icam1+ macrophages for infectious bone defect regeneration. ACS Nano, 2024, 18(52): 35575-35594.
13. Gou M, Wang H, Xie H, et al. Macrophages in guided bone regeneration: potential roles and future directions. Front Immunol, 2024, 15: 1396759. doi: 10.3389/fimmu.2024.1396759.
14. Li Y, Yao L, Zhang C, et al. Growth hormone-releasing peptide 2 may be associated with decreased M1 macrophage production and increased histologic and biomechanical tendon-bone healing properties in a rat rotator cuff tear model. Arthroscopy, 2024. doi: 10.1016/j.arthro.2024.11.094.
15. Kim DY, Ryu JH, Kim JH, et al. Targeting age-related impaired bone healing: ZnO nanoparticle-infused composite fibers modulate excessive NETosis and prolonged inflammation in aging. Int J Mol Sci, 2024, 25(23): 12851. doi: 10.3390/ijms252312851.
16. Xiong Y, Lin Z, Bu P, et al. A whole-course-repair system based on neurogenesis-angiogenesis crosstalk and macrophage reprogramming promotes diabetic wound healing. Adv Mater, 2023, 35(19): e2212300. doi: 10.1002/adma.202212300.
17. Li XR, Deng QS, He SH, et al. 3D cryo-printed hierarchical porous scaffolds provide immobilization of surface-functionalized sleep-inspired small extracellular vesicles: synergistic therapeutic strategies for vascularized bone regeneration based on macrophage phenotype modulation and angiogenesis-osteogenesis coupling. J Nanobiotechnology, 2024, 22(1): 764. doi: 10.1186/s12951-024-02977-5.
18. You J, Zhang Y, Zhou Y. Strontium functionalized in biomaterials for bone tissue engineering: A prominent role in osteoimmunomodulation. Front Bioeng Biotechnol, 2022, 10: 928799. doi: 10.3389/fbioe.2022.928799.
19. Miao Q, Jiang N, Yang Q, et al. Multi-stage controllable degradation of strontium-doped calcium sulfate hemihydrate-tricalcium phosphate microsphere composite as a substitute for osteoporotic bone defect repairing: degradation behavior and bone response. Biomed Mater, 2021, 17(1). doi: 10.1088/1748-605X/ac4323.
20. He F, Lu T, Fang X, et al. Study on MgxSr₃-x(PO4)r₂ bioceramics as potential bone grafts. Colloids Surf B Biointerfaces, 2019, 175: 158-165.
21. Safarova Yantsen Y, Nessipbekova A, Syzdykova A, et al. Strontium- and copper-doped ceramic granules in bone regeneration-associated cellular processes. J Funct Biomater, 2024, 15(11): 352. doi: 10.3390/jfb15110352.
22. Deng L, Huang L, Pan H, et al. 3D printed strontium-zinc-phosphate bioceramic scaffolds with multiple biological functions for bone tissue regeneration. J Mater Chem B, 2023, 11(24): 5469-5482.
23. Tian Y, Lu T, He F, et al. β-tricalcium phosphate composite ceramics with high compressive strength, enhanced osteogenesis and inhibited osteoclastic activities. Colloids Surf B Biointerfaces, 2018, 167: 318-327.
24. Goodarzi H, Hashemi-Najafabadi S, Baheiraei N, et al. Preparation and characterization of nanocomposite scaffolds (collagen/β-TCP/SrO) for bone tissue engineering. Tissue Eng Regen Med, 2019, 16(3): 237-251.
25. Tarafder S, Dernell WS, Bandyopadhyay A, et al. SrO- and MgO-doped microwave sintered 3D printed tricalcium phosphate scaffolds: mechanical properties and in vivo osteogenesis in a rabbit model. J Biomed Mater Res B Appl Biomater, 2015, 103(3): 679-690.
26. Asensio G, Benito-Garzón L, Ramírez-Jiménez RA, et al. Biomimetic gradient scaffolds containing hyaluronic acid and Sr/Zn folates for osteochondral tissue engineering. Polymers (Basel), 2021, 14(1): 12. doi: 10.3390/polym14010012.
27. Bootchanont A, Chaosuan N, Promdee S, et al. Correlation between biomedical and structural properties of Zn/Sr modified calcium phosphates. Biometals, 2024, 37(5): 1177-1189.
28. Chen F, Tian L, Pu X, et al. Enhanced ectopic bone formation by strontium-substituted calcium phosphate ceramics through regulation of osteoclastogenesis and osteoblastogenesis. Biomater Sci, 2022, 10(20): 5925-5937.
29. Sugimoto H, Inagaki Y, Furukawa A, et al. Silicate/zinc-substituted strontium apatite coating improves the osteoinductive properties of β-tricalcium phosphate bone graft substitute. BMC Musculoskelet Disord, 2021, 22(1): 673. doi: 10.1186/s12891-021-04563-4.
30. Pang B, Xian J, Chen J, et al. Cuttlefish bone-derived calcium phosphate bioceramics have enhanced osteogenic properties. J Funct Biomater, 2024, 15(8): 212. doi: 10.3390/jfb15080212.
31. Basu S, Ghosh A, Barui A, et al. Epithelial cell functionality on electroconductive Fe/Sr co-doped biphasic calcium phosphate. J Biomater Appl, 2019, 33(8): 1035-1052.
32. Huang B, Li S, Dai S, et al. Ti₃C2Tx MXene-decorated 3D-printed ceramic scaffolds for Enhancing osteogenesis by spatiotemporally orchestrating inflammatory and bone repair responses. Adv Sci (Weinh), 2024, 11(34): e2400229. doi: 10.1002/advs.202400229.
33. Singh SS, Roy A, Lee B, et al. Study of hMSC proliferation and differentiation on Mg and Mg-Sr containing biphasic β-tricalcium phosphate and amorphous calcium phosphate ceramics. Mater Sci Eng C Mater Biol Appl, 2016, 64: 219-228.
34. Arbez B, Manero F, Mabilleau G, et al. Human macrophages and osteoclasts resorb β-tricalcium phosphate in vitro but not mouse macrophages. Micron, 2019, 125: 102730. doi: 10.1016/j.micron.2019.102730.
35. Chazono M, Tanaka T, Kitasato S, et al. Electron microscopic study on bone formation and bioresorption after implantation of beta-tricalcium phosphate in rabbit models. J Orthop Sci, 2008, 13(6): 550-555.
36. Che J, Sun T, Lv X, et al. Influence of Ag and/or Sr dopants on the mechanical properties and in vitro degradation of β-tricalcium phosphate-based ceramics. materials (basel). 2023, 16(17): 6025. doi: 10.3390/ma16176025.
37. Bohner M, Santoni BLG, Döbelin N. β-tricalcium phosphate for bone substitution: Synthesis and properties. Acta Biomater, 2020, 113: 23-41.
38. Naruphontjirakul P, Li S, Pinna A, et al. Interaction of monodispersed strontium containing bioactive glass nanoparticles with macrophages. Biomater Adv, 2022, 133: 112610. doi: 10.1016/j.msec.2021.112610.
39. Yu D, Guo S, Yu M, et al. Immunomodulation and osseointegration activities of Na₂TiO₃ nanorods-arrayed coatings doped with different Sr content. Bioact Mater, 2021, 10: 323-334.
40. Jiang S, Wang X, Ma Y, et al. Synergistic effect of micro-nano-hybrid surfaces and Sr doping on the osteogenic and angiogenic capacity of hydroxyapatite bioceramics scaffolds. Int J Nanomedicine, 2022, 17: 783-797.
41. Miao A, Li Q, Tang G, et al. Alginate-containing 3D-printed hydrogel scaffolds incorporated with strontium promotes vascularization and bone regeneration. Int J Biol Macromol, 2024, 273(Pt 1): 133038. doi: 10.1016/j.ijbiomac.2024.133038.
42. Li S, Zhang L, Liu C, et al. Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects. Bioact Mater, 2022, 23: 101-117.
43. Sha W, Zhao B, Wei H, et al. Astragalus polysaccharide ameliorates vascular endothelial dysfunction by stimulating macrophage M2 polarization via potentiating Nrf2/HO-1 signaling pathway. Phytomedicine, 2023, 112: 154667. doi: 10.1016/j.phymed.2023.154667.
44. Jomova K, Raptova R, Alomar SY, et al. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol, 2023, 97(10): 2499-2574.
45. Zhou C, Chen YQ, Zhu YH, et al. Antiadipogenesis and osseointegration of strontium-doped implant surfaces. J Dent Res, 2019, 98(7): 795-802.
46. Li Y, Chen M, Yan J, et al. Tannic acid/Sr²⁺-coated silk/graphene oxide-based meniscus scaffold with anti-inflammatory and anti-ROS functions for cartilage protection and delaying osteoarthritis. Acta Biomater, 2021, 126: 119-131.
47. Asensio G, Martín-Del-Campo M, Ramírez RA, et al. New insights into the in vitro antioxidant routes and osteogenic properties of Sr/Zn phytate compounds. Pharmaceutics, 2023, 15(2): 339. doi: 10.3390/pharmaceutics15020339.
48. Wu X, Tang Z, Wu K, et al. Strontium-calcium phosphate hybrid cement with enhanced osteogenic and angiogenic properties for vascularised bone regeneration. J Mater Chem B, 2021, 9(30): 5982-5997.

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Research progress on strontium modified β-tricalcium phosphate composite biomaterials with immune regulatory properties

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